The effect of renin–angiotensin–aldosterone system blockers on the progression of chronic kidney disease in hypertensive elderly patients without proteinuria: PROERCAN study. Rationale and design

array:23 ["pii" => "S1889183720300271" "issn" => "18891837" "doi" => "10.1016/j.hipert.2020.02.005" "estado" => "S300" "fechaPublicacion" => "2020-07-01" "aid" => "411" "copyright" => "SEH-LELHA" "copyrightAnyo" => "2020" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Hipertens Riesgo Vasc. 2020;37:101-7" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "itemSiguiente" => array:18 [ "pii" => "S1889183720300325" "issn" => "18891837" "doi" => "10.1016/j.hipert.2020.03.001" "estado" => "S300" "fechaPublicacion" => "2020-07-01" "aid" => "413" "copyright" => "SEH-LELHA" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Hipertens Riesgo Vasc. 2020;37:108-14" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "es" => array:13 [ "idiomaDefecto" => true "cabecera" => "ORIGINAL" "titulo" => "Asociación de desórdenes autonómicos con aterosclerosis subclínica" "tienePdf" => "es" "tieneTextoCompleto" => "es" "tieneResumen" => array:2 [ 0 => "es" 1 => "en" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "108" "paginaFinal" => "114" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Association between autonomic disorders and subclinical atherosclerosis" ] ] "contieneResumen" => array:2 [ "es" => true "en" => true ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figura 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 967 "Ancho" => 1616 "Tamanyo" => 58149 ] ] "descripcion" => array:1 [ "es" => "Espectro de baja frecuencia según presencia o ausencia de ateromatosis carotídea. LFln: 4,92 ATE+vs. 6,22 en ATE−; p<0,0001. Los datos se expresan como logaritmo de baja frecuencia. ATE−: individuos sin ateromatosis carotídea; ATE+: individuos con ateromatosis carotídea; LFln: logaritmo de baja frecuencia." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "D.S. Mendo, S.A. González, H.A. Bonaccorsi" "autores" => array:3 [ 0 => array:2 [ "nombre" => "D.S." "apellidos" => "Mendo" ] 1 => array:2 [ "nombre" => "S.A." "apellidos" => "González" ] 2 => array:2 [ "nombre" => "H.A." "apellidos" => "Bonaccorsi" ] ] ] ] ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1889183720300325?idApp=UINPBA00004N" "url" => "/18891837/0000003700000003/v1_202006200856/S1889183720300325/v1_202006200856/es/main.assets" ] "itemAnterior" => array:17 [ "pii" => "S1889183720300349" "issn" => "18891837" "doi" => "10.1016/j.hipert.2020.04.002" "estado" => "S300" "fechaPublicacion" => "2020-07-01" "aid" => "415" "documento" => "article" "crossmark" => 1 "subdocumento" => "sco" "cita" => "Hipertens Riesgo Vasc. 2020;37:99-100" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "es" => array:10 [ "idiomaDefecto" => true "cabecera" => "Editorial" "titulo" => "Bloqueantes del sistema renina-angiotensina e infección por COVID-19" "tienePdf" => "es" "tieneTextoCompleto" => "es" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "99" "paginaFinal" => "100" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Renin-angiotensin system blockers and COVID-19 infection" ] ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "L.M. Ruilope, J.A. Garcia Donaire, A. de la Sierra" "autores" => array:3 [ 0 => array:2 [ "nombre" => "L.M." "apellidos" => "Ruilope" ] 1 => array:2 [ "nombre" => "J.A." "apellidos" => "Garcia Donaire" ] 2 => array:2 [ "nombre" => "A." "apellidos" => "de la Sierra" ] ] ] ] ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1889183720300349?idApp=UINPBA00004N" "url" => "/18891837/0000003700000003/v1_202006200856/S1889183720300349/v1_202006200856/es/main.assets" ] "en" => array:19 [ "idiomaDefecto" => true "cabecera" => "Original article" "titulo" => "The effect of renin–angiotensin–aldosterone system blockers on the progression of chronic kidney disease in hypertensive elderly patients without proteinuria: PROERCAN study. Rationale and design" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "101" "paginaFinal" => "107" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "A.M. García-Prieto, Ú. Verdalles, A.P. de José, E. Verde, D. Arroyo, I. Aragoncillo, T. Linares, D. Barbieri, M. Goicoechea" "autores" => array:9 [ 0 => array:4 [ "nombre" => "A.M." "apellidos" => "García-Prieto" "email" => array:1 [ 0 => "anamgarciaprieto@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Ú." "apellidos" => "Verdalles" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "A.P." "apellidos" => "de José" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 3 => array:3 [ "nombre" => "E." "apellidos" => "Verde" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 4 => array:3 [ "nombre" => "D." "apellidos" => "Arroyo" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 5 => array:3 [ "nombre" => "I." "apellidos" => "Aragoncillo" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 6 => array:3 [ "nombre" => "T." "apellidos" => "Linares" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 7 => array:3 [ "nombre" => "D." "apellidos" => "Barbieri" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 8 => array:3 [ "nombre" => "M." "apellidos" => "Goicoechea" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Servicio Nefrología Hospital General Universitario Gregorio Marañón, Calle Doctor Esquerdo 46, 28007 Madrid, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Spanish Research Network (REDINREN), Madrid, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Efecto de los bloqueantes del sistema renina-angiotensina-aldosterona en la progresión de la enfermedad renal crónica en pacientes añosos sin proteinuria: ensayo clínico PROERCAN. Diseño y justificación del estudio" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2386 "Ancho" => 2500 "Tamanyo" => 339134 ] ] "descripcion" => array:1 [ "en" => "Schema for PROERCAN trial. CKD, chronic kidney disease. RAS, renin–angiotensin-system. ACEi, angiotensin converting enzyme. BP, blood pressure. Egfr, estimated glomerular filtration rate." ] ] ] "textoCompleto" => "Introduction and rationaleGiven the increased life expectancy, there is a rising prevalence of elderly patients with chronic diseases such as diabetes, hypertension or chronic kidney disease (CKD). Whereas the prevalence of CKD is estimated to be 6–18% worldwide,<a class="elsevierStyleCrossRef" href="#bib0130">1</a> it raises up to 23.4–35.8% in patients over 65 years of age, affecting 30% of patients over 70 years old and almost 50% over 85 years old.<a class="elsevierStyleCrossRefs" href="#bib0135">2,3</a> Thus, the spectrum of patients that attend the Nephrology outpatient clinics has significantly changed in the last years, being now older and with a higher prevalence of vascular and interstitial nephropathies that are characterized by minimum proteinuria and slowly progressive CKD.Blood pressure (BP) control is fundamental to the care of patients with CKD and is relevant at all stages of CKD regardless the underlying cause of renal disease.<a class="elsevierStyleCrossRef" href="#bib0145">4</a> Renin–angiotensine–aldosterone system (RAAS) blockers have shown to be effective in controlling BP and proteinuria, slowing the progression to end stage renal disease (ESRD) and reducing cardiovascular risk,<a class="elsevierStyleCrossRef" href="#bib0150">5</a> so they are the mainstream treatment of hypertension in CKD.<a class="elsevierStyleCrossRef" href="#bib0145">4</a> However, most of the randomized clinical trials (RCTs) that have shown RAAS blockers benefits have excluded elderly patients with CKD,<a class="elsevierStyleCrossRef" href="#bib0155">6</a> so there is a lack of evidence in this population. There are some data available on their use in the elderly, but they come from RCTs that were not designed to analyze kidney function as a main outcome, and results are thus controversial. In addition, this population appears to be more susceptible to its adverse events, such as hyperkalaemia, hypotension or acute kidney failure. Thus, there is a lack of evidence on the effect of RAAS blockers on BP control and CKD progression in elderly patients.The aim of this study is to evaluate the impact of the administration of RAAS blockers in the progression of renal disease in elderly patients with CKD without proteinuria.Materials and methodsStudy designThe PROERCAN (PROgresión de Enfermedad Renal Crónica en ANcianos) trial (trial registration: <a href="ctgov:NCT03195023">NCT03195023</a>) is a multicenter, open label, randomized controlled clinical trial.RecruitmentParticipants will be recruited from 2 renal units. The study has been approved by the Institutional Ethics Committee (with adherence to the Declaration of Helsinki), an each participating patient will give informed consent before enrollment.Inclusion and exclusion criteriaInclusion criteria are as follows:<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005">-Aged≥65 years.</li><li class="elsevierStyleListItem" id="lsti0010">-Previous history of hypertension under any antihypertensive treatment:<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0015">•Patients who have not received RAAS blockers during a 3 month period prior to inclusion could be directly included.</li><li class="elsevierStyleListItem" id="lsti0020">•Patients who have received RAAS blockers in the 3 months prior to inclusion could be included after a one month washout period.</li></ul></li><li class="elsevierStyleListItem" id="lsti0025">-CKD stage 3 or 4 (estimated glomerular filtration rate (eGRF) 15–60ml/min/1.73m2) using the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation with at least one year of specialist renal follow up.</li><li class="elsevierStyleListItem" id="lsti0030">-Urinary albumin/creatinine ratio (UACR)<30mg/g.Exclusion criteria are as follows:</li><li class="elsevierStyleListItem" id="lsti0035">-Diabetes mellitus</li><li class="elsevierStyleListItem" id="lsti0040">-Glomerular nephropathies</li><li class="elsevierStyleListItem" id="lsti0045">-History of congestive heart failure or myocardial infarction</li><li class="elsevierStyleListItem" id="lsti0050">-Resistant or uncontrolled hypertension (BP>160/100mmHg)</li><li class="elsevierStyleListItem" id="lsti0055">-Solitary functioning kidney</li><li class="elsevierStyleListItem" id="lsti0060">-Active malignant disease (except skin cancer different from melanoma). Patients can be included if they have been free of the disease for at least 5 years</li><li class="elsevierStyleListItem" id="lsti0065">-Active inflammatory disease (e.g. rheumatoid artritis, systemic lupus erythematous, Chron's disease, etc.)</li><li class="elsevierStyleListItem" id="lsti0070">-Cirrhosis</li><li class="elsevierStyleListItem" id="lsti0075">-Allergy or intolerance to angiotensin converting enzyme inhibitors (ACEi) or calcium channel blockers (CCB)</li><li class="elsevierStyleListItem" id="lsti0080">-Chronic infection from hepatitis B or C virus or human immunodeficiency virus</li><li class="elsevierStyleListItem" id="lsti0085">-Immunosuppressive treatment during the 12 weeks prior to inclusion</li><li class="elsevierStyleListItem" id="lsti0090">-Hospitalization during the 3 months prior to inclusion</li><li class="elsevierStyleListItem" id="lsti0095">-Rapidly progressive chronic kidney disease defined as a fall in eGFR>5ml/min/1.73m2</li><li class="elsevierStyleListItem" id="lsti0100">-Inability to provide informed consent</li><li class="elsevierStyleListItem" id="lsti0105">-Inability to comply with the trial schedule and follow up.</li></ul>Study enrolment and randomizationFollowing informed consent and completion of the baseline assessment, patients will be randomized into the trial in a 1:1 ratio to either receive ACEi or antihypertensive treatment without RAAS blockers. Randomization will be provided by a computer-generated program using a minimization algorithm to ensure balance between the arms (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).<elsevierMultimedia ident="fig0005"></elsevierMultimedia>Study treatmentACEi armPatients that were receiving an ACEi prior to inclusion can continue with their previous antihypertensive treatment after the washout period of one month. Patients that were not receiving an ACEi will start receiving Lisinopril 20mg a day that can be adjusted depending on BP control. The reason to use lisinopril was based on its long half life that allows a daily dose, thus facilitating compliance. Any other antihypertensive treatment used in routine clinical practice can be added to control BP.Non-ACEi armPatients that were receiving an ACEi prior to inclusion will discontinue it and, in order to compensate for the loss of antihypertensive activity, treatment with Amlodipine 10mg a day or Lercanidipine 20mg a day (depending on the presence of edema) will be commenced. Any other antihypertensive treatment used in routine clinical practice can be added to achieve BP control. Patients that were not receiving an ACEi prior to inclusion can continue with their previous antihypertensive treatment.Both treatment groupsIn both groups, BP will be controlled to the target pressure outlined in the European Society of Cardiology-European Society of Hypertension (ESC-ESH) guideline<a class="elsevierStyleCrossRef" href="#bib0160">7</a> of 140/90mmHg.BlindingTrial treatment will be open label, due to the practical difficulties and costs associated with using placebo in a trial of drug withdrawal. However, the primary outcome is an objective laboratory measure that reduces the need for blinding.AssessmentsParticipants will be assessed at month 1, 3, 6, 12, 18, 24 and 36 in the patient's routine outpatient clinic visit. Demographic data and detailed previous medical history will be collected at baseline as well as BP and decline in eGFR in the 12 month period prior to inclusion. BP will be recorded at each visit, and changes to antihypertensive and other concomitant medication will be recorded. Urine and blood samples will be taken at baseline and in each visit (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>Primary outcomeThe primary outcome measure is difference in renal function measured using the CKD-EPI eGFR at the 3 years of follow up.Secondary outcomeRenal events<ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0110">•Number of patients with an increase of>50% decline in eGFR or starting renal replacement therapy.</li><li class="elsevierStyleListItem" id="lsti0115">•Time to ESRD.</li></ul>Clinical events<ul class="elsevierStyleList" id="lis0020"><li class="elsevierStyleListItem" id="lsti0120">•BP control: number of patients with controlled office BP (defined as<140/90mmHg).</li></ul>Laboratory measures<ul class="elsevierStyleList" id="lis0025"><li class="elsevierStyleListItem" id="lsti0125">•UACR:<ul class="elsevierStyleList" id="lis0030"><li class="elsevierStyleListItem" id="lsti0130">∘Number of patients with normo, micro and macroalbuminuria.</li><li class="elsevierStyleListItem" id="lsti0135">∘Number of patients with normoalbuminuria that develope micro or macroalbuminuria during follow up.</li></ul></li><li class="elsevierStyleListItem" id="lsti0140">•Total serum CO2 levels.</li></ul>Safety<ul class="elsevierStyleList" id="lis0035"><li class="elsevierStyleListItem" id="lsti0145">•Number of hyperkalemic (K>5.5mmol/l) episodes.</li><li class="elsevierStyleListItem" id="lsti0150">•Number and type of cardiovascular events.</li><li class="elsevierStyleListItem" id="lsti0155">•Global and cardiovascular mortality.</li></ul>Serious adverse events will be monitored and reported within a 24h period. Those that will end in patient discontinuation will be: allergy to any drug used in the trial and hyperkalemia>7mmol/l.Statistical considerationsSample sizeThe absence of studies in elderly patients with CKD stages 3 and 4 leads us to use other studies performed by our group to estimate sample size. In our study about the effect of allopurinol on CKD progression<a class="elsevierStyleCrossRef" href="#bib0165">8</a> that included 113 patients with CKD 3 and 4 with a follow up period of 24 months, the eGFR fall a mean of 4ml/min/1.73m2 in the control group, that is 2ml/min/1.73m2 per year. Almost 80% of those patients were receiving RAAS blockers. Thus, with a mean follow up of 3 years we must detect a difference of 6ml/min/1.73m2 between both groups.To estimate a minimum relevant difference between groups of 6ml/min/1.73m2 with 80% power and alpha=0.05 (using a two-sample t-test), a total of 110 will need to be recruited (this includes allowance for 20% dropout).Statistical analysisAll analysis will be based on the intention to treat principle, and a p value of<0.05 will be considered statistically significant. Variables’ distribution will be analyzed using the Kolmogorov–Smirnov test. The primary outcome is eGFR at 3 years. These data will be summarized using means and standard deviations, with differences in means and 95% confidence intervals (CIs) reported. The two groups will be compared at 3 years using a two-sample t test. Continuous secondary outcome measures (e.g. BP, UACR, etc.) will be analyzed in the same way as the primary outcome. Categorical (dichotomous) outcome measures will compare the propotion of participants and percentages using a χ2 test, with relative risks and 95% CIs reported. Time to event outcomes will be analyzed using survival analysis and log-rank methods. Kaplan–Meier survival curves will be constructed for visual presentation of time-to-event comparisons. Treatment effects will be expressed as hazard ratios with 95% CIs. Multivariate regression model will be used to analyze variables that have an impact on CKD progression, including those that result statistically significant in the univariate model. Uni and multivariate Cox regression model will analyze variables related to higher cardiovascular risk and mortality.Regulatory aspectsWritten informed consent will be provided by all patients prior to randomization. The study was conducted according to the Declaration of Helsinki.Ethical committee approvalEthical approval for PROERCAN01 was granted by local ethical committee (Comité Ético de Investigación Clínica Hospital General Universitario Gregorio Marañón) on 24 June 2015.DiscussionBP control is fundamental to the care of patients with CKD and is relevant at all stages of renal disease. RAAS blockers have shown to be effective not only in BP control but also in reducing proteinuria and slowing CKD progression. However, evidence to recommend RAAS blockers in elderly patients with CKD without proteinuria is lacking. The primary outcome of our study is to evaluate the impact of RAAS blockers in CKD progression in elderly patients without proteinuria.In elderly patients results, obtained with RAAS blockers are similar in terms of kidney function when compared to other antihypertensive drugs, and positive results have only been shown when some subgroups have been analyzed. The Hypertension in the Very elderly Trial (HYVET)<a class="elsevierStyleCrossRef" href="#bib0170">9</a> investigated the effect of active treatment on stroke incidence in hypertensive patients over the age of 80 years. Secondary end-points included kidney function, cardiovascular mortality and morbidity. A total of 3845 patients were randomized to receive treatment with indapamide and/or perindopril or placebo. Indapamide treatment, with or without perindopril, was associated with better BP control and a 30% reduction in the incidence of stroke. Despite this benefit in stroke prevention in the treatment group, there were no differences in renal events between patients who received an ACEi or not. The Study on Cognition and Prognosis in the Elderly (SCOPE)<a class="elsevierStyleCrossRef" href="#bib0175">10</a> was designed to assess whether RAAS blockers confer a reduction in cardiovascular events, cognitive decline and dementia. It included 4964 hypertensive elderly patients who were randomized to receive candesartan or placebo. Treatment with candesartan was associated with a modest, statistically non-significant, reduction in major cardiovascular events and with a marked reduction in non-fatal stroke. There were no differences in creatinine levels and CKD progression between groups. Wright et al.<a class="elsevierStyleCrossRef" href="#bib0180">11</a> performed a secondary analysis of elderly patients included in the Antihypertensive and Lipid-lowering treatment to prevent Heart Attack Trial (ALLHAT)<a class="elsevierStyleCrossRef" href="#bib0185">12</a> and they found no benefit of lisinopril versus clortalidone in the prevention of CKD. The Effect of Telmisartan on Renal Outcomes (TRASCEND) study<a class="elsevierStyleCrossRef" href="#bib0190">13</a> examined the effect of telmisartan versus placebo on kidney function. In this study, 5926 patients with diabetes or ischemic heart disease were randomized, with a mean age of 66.9 years. Patients with creatinine>3mg/dl or macroalbuminuria were excluded. Mean baseline creatinine was 1mg/dl and 10% had microalbuminuria. They found no statistically significant differences on renal events between groups. Thus, so far, no data have been published about the beneficial effect of RAAS blockers in elderly patients with CKD.In addition, most of the RCTs that have shown RAAS blockers benefit on kidney function include patients with diabetes and proteinuria.<a class="elsevierStyleCrossRefs" href="#bib0195">14–16</a> An exception was the African American Study of Kidney disease (AASK)<a class="elsevierStyleCrossRef" href="#bib0210">17</a> that included 1029 african-american patients with non diabetic, non proteinuric vascular nephropathy. It showed a possible beneficial effect of ACEi treatment in slowing eGFR decline. However, patients included in this RCT were young (mean age of 52 years). Thus, there is not enough evidence to support the use of RAAS blockers to slow CKD progression in patients without diabetes and proteinuria. This is especially controversial in the elderly that tend to be more susceptible to RAAS blockers adverse events (e.g. hyperkalaemia, hypotension or acute kidney failure). Ahmed et al.<a class="elsevierStyleCrossRef" href="#bib0215">18</a> described the impact of RAAS blockers withdrawal in elderly patients (mean age of 73.3 years) with advanced CKD that resulted in an improvement of eGFR from 16.38ml/min/m2 to 26.6ml/min/m2 over a 12 month period. They suggested that RAAS blockers contribute to progression of advanced CKD in the elderly. The Renal Outcomes with Telmisartan, Ramipril, or both, in people at high vascular risk (ONTARGET)<a class="elsevierStyleCrossRef" href="#bib0220">19</a> trial randomized 25,620 patients to receive telmisartan, ramipril or their combination to evaluate the impact on renal function. A total of 6420 patients had an eGFR<60ml/min/m2, with a mean age of 55 years. Even though the patients treated with the combination had higher reduction of proteinuria, the risk of CKD progression and hyperkalaemia raised compared to patients receiving monotherapy. In this way, there is an ongoing RCT called STOP-ACEi<a class="elsevierStyleCrossRef" href="#bib0225">20</a> designed to evaluate whether the discontinuation of RAAS blockers improves or stabilizes renal function in patients with advanced progressive CKD and diabetes mellitus. 410 patients with advanced (stages 4 and 5) CKD that are currently receiving RAAS blockers will be included. Patients will be randomly assigned in 1:1 fashion to either discontinue the current RAAS regimen or continue treatment for 3 years. Results are expected to be available by 2022. These data suggest that discontinuing RAAS inhibitors in advanced CKD can be beneficial in CKD progression but no data have been published so far about the role of RAAS blockers in the elderly patients with less severe degrees of CKD without albuminuria.In terms of cardiovascular risk, ACEi have shown to reduce cardiovascular mortality in several RCTs like the MICRovascular Outcome in arm of the Heart Outcomes Prevention Evaluation study (MICRO-HOPE)<a class="elsevierStyleCrossRefs" href="#bib0190">13,21</a> or the European Trial on Reduction of Cardiac Events with Perindopril in Stable Coronary Artery Disease (EUROPA),<a class="elsevierStyleCrossRef" href="#bib0235">22</a> that were performed in high cardiovascular risk patients. However, ACEi have not proved to reduce cardiovascular risk in patients without ischemic heart disease except for their effect on BP control and, secondary, on the incidence of non-fatal stroke as previously mentioned.<a class="elsevierStyleCrossRefs" href="#bib0170">9,10</a> Moreover, although CKD is considered as a high cardiovascular risk condition by the American Heart Association,<a class="elsevierStyleCrossRef" href="#bib0240">23</a> this statement is less strong in the elderly. This is due to a relative risk of mortality and cardiovascular events among patients with CKD, that increases until a certain age, from which it stabilizes.<a class="elsevierStyleCrossRef" href="#bib0245">24</a> Accordingly, RAAS blockers benefit on cardiovascular risk in elderly patients with CKD must still to be confirmed. In fact, a National Kidney Foundation-Kidney Disease Global Outcomes (NKF-KDIGO) report has been recently published encouraging investigators to research in this field.<a class="elsevierStyleCrossRef" href="#bib0250">25</a>The result of our RCT will provide evidence on whether the discontinuation of RAAS blockers is beneficial to renal function and improves other important parameter including laboratory and clinical outcomes without causing an increase in cardiovascular events. It is, therefore, hoped that this pivotal study can provide new findings to allow future consideration in the treatment of hypertension in elderly patients with CKD without proteinuria.Trial statusPROERCAN opened recruitment on June 2015, and the first patient was recruited on September 2015. As of January 2020, 79 patients (72%) were recruited into the study. Recruitment is still ongoing and is expected to be completed by July 2020.FundingNone.Conflict of interestNone to declare." "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:3 [ "identificador" => "xres1351902" "titulo" => "Abstract" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Materials and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results and conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1243201" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "xpalclavsec1243200" "titulo" => "Abbreviations" ] 3 => array:3 [ "identificador" => "xres1351903" "titulo" => "Resumen" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "abst0020" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0025" "titulo" => "Material y métodos" ] 2 => array:2 [ "identificador" => "abst0030" "titulo" => "Resultados y conclusión" ] ] ] 4 => array:2 [ "identificador" => "xpalclavsec1243202" "titulo" => "Palabras clave" ] 5 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction and rationale" ] 6 => array:3 [ "identificador" => "sec0010" "titulo" => "Materials and methods" "secciones" => array:12 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Study design" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Recruitment" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Inclusion and exclusion criteria" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Study enrolment and randomization" ] 4 => array:3 [ "identificador" => "sec0035" "titulo" => "Study treatment" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0040" "titulo" => "ACEi arm" ] 1 => array:2 [ "identificador" => "sec0045" "titulo" => "Non-ACEi arm" ] 2 => array:2 [ "identificador" => "sec0050" "titulo" => "Both treatment groups" ] ] ] 5 => array:2 [ "identificador" => "sec0055" "titulo" => "Blinding" ] 6 => array:2 [ "identificador" => "sec0060" "titulo" => "Assessments" ] 7 => array:2 [ "identificador" => "sec0065" "titulo" => "Primary outcome" ] 8 => array:3 [ "identificador" => "sec0070" "titulo" => "Secondary outcome" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0075" "titulo" => "Renal events" ] 1 => array:2 [ "identificador" => "sec0080" "titulo" => "Clinical events" ] 2 => array:2 [ "identificador" => "sec0085" "titulo" => "Laboratory measures" ] 3 => array:2 [ "identificador" => "sec0090" "titulo" => "Safety" ] ] ] 9 => array:3 [ "identificador" => "sec0095" "titulo" => "Statistical considerations" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0100" "titulo" => "Sample size" ] 1 => array:2 [ "identificador" => "sec0105" "titulo" => "Statistical analysis" ] ] ] 10 => array:2 [ "identificador" => "sec0110" "titulo" => "Regulatory aspects" ] 11 => array:2 [ "identificador" => "sec0115" "titulo" => "Ethical committee approval" ] ] ] 7 => array:3 [ "identificador" => "sec0120" "titulo" => "Discussion" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0125" "titulo" => "Trial status" ] ] ] 8 => array:2 [ "identificador" => "sec0130" "titulo" => "Funding" ] 9 => array:2 [ "identificador" => "sec0135" "titulo" => "Conflict of interest" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2020-01-23" "fechaAceptado" => "2020-02-20" "PalabrasClave" => array:2 [ "en" => array:2 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1243201" "palabras" => array:5 [ 0 => "Albuminuria" 1 => "Chronic kidney disease" 2 => "Elderly" 3 => "Hypertension" 4 => "Renin–angiotensin-system" ] ] 1 => array:4 [ "clase" => "abr" "titulo" => "Abbreviations" "identificador" => "xpalclavsec1243200" "palabras" => array:9 [ 0 => "ACEi" 1 => "BP" 2 => "CCB" 3 => "CKD" 4 => "eGFR" 5 => "ESRD" 6 => "RAAS" 7 => "RCT" 8 => "UACR" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1243202" "palabras" => array:5 [ 0 => "Albuminuria" 1 => "Enfermedad renal crónica" 2 => "Ancianos" 3 => "Hipertensión" 4 => "Sistema renina-angiotensina" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "IntroductionBlood pressure (BP) control is fundamental to the care of patients with chronic kidney disease (CKD), and is relevant at all stages of CKD. Renin–angiotensin–aldosterone system (RAAS) blockers have shown to be effective, not only in BP control but also in reducing proteinuria and slowing CKD progression. However, there is a lack of evidence for recommending RAAS blockers in elderly patients with CKD without proteinuria. The primary outcome of the present study is to evaluate the impact of RAAS blockers on CKD progression in elderly patients without proteinuria. Materials and methodsThe PROERCAN trial (trial registration, NCT03195023) is a multicentre open-label, randomized controlled clinical trial with 110 participants over 65 years-old with hypertension and CKD stages 3–4 without proteinuria. Patients will be randomized in a 1:1 ratio to either receive RAAS blockers or other antihypertensive drugs, and will be followed up for three years. Primary outcome is the estimated glomerular filtration rate (eGFR) decline at 3 years. Secondary outcomes include BP control, renal and cardiovascular events, and mortality. Results and conclusionsThe design of this trial is presented here. The results will show if antihypertensive treatment with RAAS blockers has an impact on CKD progression in elderly patients without proteinuria. Any differences in BP control, cardiovascular events, and mortality with each antihypertensive treatment will be also clarified." "secciones" => array:3 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Materials and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results and conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "IntroducciónEl control de la presión arterial (PA) es fundamental para los pacientes con enfermedad renal crónica (ERC) y es relevante en todos los estadios de ERC. Los bloqueantes del sistema renina-angiotensina-aldosterona (BSRAA) han demostrado su efectividad no solo en el control de la PA sino también en la reducción de la proteinuria y de la progresión de la ERC. Sin embargo, no existe evidencia para recomendar el uso de BSRAA en pacientes añosos con ERC sin proteinuria. El objetivo principal del estudio es evaluar el impacto de los BSRAA en la progresión de ERC en pacientes añosos sin proteinuria. Material y métodosEl estudio PROERCAN (NCT03195023) es un ensayo clínico multicéntrico, abierto, aleatorizado de 110 pacientes hipertensos, mayores de 65años con ERC estadios3 y4 sin proteinuria. Los pacientes son aleatorizados 1:1 a recibir tratamiento con BSRAA u otros antihipertensivos y el seguimiento será de 3años. La variable principal es el descenso del filtrado glomerular estimado durante el tiempo de seguimiento. Las variables secundarias incluyen las cifras de PA, eventos renales y cardiovasculares y mortalidad. Resultados y conclusiónEl diseño del ensayo clínico se desarrolla en el presente artículo. Los resultados determinarán si el tratamiento antihipertensivo con BSRAA tiene un impacto en la progresión de la ERC en pacientes añosos sin proteinuria. Así mismo, se aclararán las diferencias en el control de la PA, los eventos cardiovasculares y la mortalidad con los distintos tratamientos antihipertensivos." "secciones" => array:3 [ 0 => array:2 [ "identificador" => "abst0020" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0025" "titulo" => "Material y métodos" ] 2 => array:2 [ "identificador" => "abst0030" "titulo" => "Resultados y conclusión" ] ] ] ] "multimedia" => array:2 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2386 "Ancho" => 2500 "Tamanyo" => 339134 ] ] "descripcion" => array:1 [ "en" => "Schema for PROERCAN trial. CKD, chronic kidney disease. RAS, renin–angiotensin-system. ACEi, angiotensin converting enzyme. BP, blood pressure. Egfr, estimated glomerular filtration rate." ] ] 1 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "eGFR: estimated glomerular filtration rate; UACR: urinary albumin/creatinine ratio; BP: blood pressure; RAAS: renin–angiotensin–aldosterone system; SAE: seriour adverse events." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Visit \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Procedures \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Sign informed consent.Retrospective data collection (12 month prior to inclusion): potassium, creatinine, eGFR, UACR, BP.If under RAAS blocker treatment: 1 month wash out period. If not, patient can be redirected to visit 0. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0First visit \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Randomization.Detailed medical history including medication.Physical examination including BP.Blood and urinary samples. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1Month 1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Detailed medical history including medication, SAE and other clincial events.Physical examination including BP.Blood and urinary samples. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2Month 3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Detailed medical history including medication, SAE and other clinical events.Physical examination including BP.Blood and urinary samples. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3Month 6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Detailed medical history including medication, SAE and other clinical events.Physical examination including BP.Blood and urinary samples. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4Month 12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Detailed medical history including medication, SAE and other clinical events.Physical examination including BP.Blood and urinary samples. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5Month 18 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Detailed medical history including medication, SAE and other clinical events.Physical examination including BP.Blood and urinary samples. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6Month 24 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Detailed medical history including medication, SAE and other clinical events.Physical examination including BP.Blood and urinary samples. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7Month 36 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Detailed medical history including medication, SAE and other clinical events.Physical examination including BP.Blood and urinary samples. \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2320430.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Schedule of assessments." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:25 [ 0 => array:3 [ "identificador" => "bib0130" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Chronic kidney disease: global dimension and perspectives" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "V. Jha" 1 => "G. Garcia-Garcia" 2 => "K. Iseki" 3 => "S. Naicker" 4 => "B. Plattner" 5 => "R. Saran" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0140-6736(13)60687-X" "Revista" => array:6 [ "tituloSerie" => "Lancet" "fecha" => "2013" "volumen" => "382" "paginaInicial" => "260" "paginaFinal" => "272" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23727169" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0135" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Prevalence of chronic kidney disease in population-based studies: systematic review" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "Q.L. Zhang" 1 => "D. Rothenbacher" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/1471-2458-8-117" "Revista" => array:5 [ "tituloSerie" => "BMC Public Health" "fecha" => "2008" "volumen" => "8" "paginaInicial" => "117" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18405348" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0140" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Mortality risk stratification in chronic kidney disease: one size for all ages?" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A.M. O’Hare" 1 => "D. Bertenthal" 2 => "K.E. Covinsky" 3 => "C.S. Landefeld" 4 => "S. Sen" 5 => "K. Mehta" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1681/ASN.2005090986" "Revista" => array:6 [ "tituloSerie" => "J Am Soc Nephrol" "fecha" => "2006" "volumen" => "17" "paginaInicial" => "846" "paginaFinal" => "853" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16452492" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0145" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "KDIGO clinical practice guideline for the management of blood pressure in chronic kidney disease: summary of recommendation statements" "autores" => array:1 [ 0 => array:2 [ "colaboracion" => "KDIGO Work Group" "etal" => false ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Kidney Int Suppl" "fecha" => "2012" "volumen" => "2" "paginaInicial" => "341" "paginaFinal" => "342" ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0150" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "AIPRD Study Group Progression of chronic kidney disease: the role of blood pressure control, proteinuria, and angiotensin-converting enzyme inhibition: a patient-level meta-analysis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "T.H. Jafar" 1 => "P.C. Stark" 2 => "C.H. Schmid" 3 => "M. Landa" 4 => "G. Maschio" 5 => "P.E. de Jong" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.7326/0003-4819-139-4-200308190-00006" "Revista" => array:6 [ "tituloSerie" => "Ann Intern Med" "fecha" => "2003" "volumen" => "139" "paginaInicial" => "244" "paginaFinal" => "252" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12965979" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0155" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Current guidelines for using angiotensin-converting enzyme inhibitors and angiotensin II-receptor antagonists in chronic kidney disease: is the evidence base relevant to older adults?" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "A.M. O’Hare" 1 => "J.S. Kaufman" 2 => "K.E. Covinsky" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Ann Intern Med" "fecha" => "2009" "volumen" => "19" "paginaInicial" => "717" "paginaFinal" => "724" ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0160" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "ESC Scientific Document Group 2018 ESC/ESH Guidelines for the management of arterial hypertension" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "B. Williams" 1 => "G. Mancia" 2 => "W. Spiering" 3 => "E. Agabiti Rosei" 4 => "M. Azizi" 5 => "M. Burnier" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/eurheartj/ehy339" "Revista" => array:6 [ "tituloSerie" => "Eur Heart J" "fecha" => "2018" "volumen" => "39" "paginaInicial" => "3021" "paginaFinal" => "3104" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30165516" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0165" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effect of allopurinol in chronic kidney disease progression and cardiovascular risk" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Goicoechea" 1 => "S.G. de Vinuesa" 2 => "U. Verdalles" 3 => "C. Ruiz-Caro" 4 => "J. Ampuero" 5 => "A. Rincón" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.2215/CJN.01580210" "Revista" => array:6 [ "tituloSerie" => "Clin J Am Soc Nephrol" "fecha" => "2010" "volumen" => "5" "paginaInicial" => "1388" "paginaFinal" => "1393" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20538833" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0170" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "HYVET Stdy Group Treatment of Hypertension in patients 80 years of age or older" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "N. Beckett" 1 => "R. Peters" 2 => "A. Fletcher" 3 => "C.S. Landefeld" 4 => "L.V. McFarland" 5 => "E.B. Larson" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa0801369" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2008" "volumen" => "358" "paginaInicial" => "1887" "paginaFinal" => "1898" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18378519" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0175" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "SCOPE Study Group The Study on Cognition and Prognosis in the Elderly (SCOPE): principal results of a randomized double-blind intervention trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "H. Lithel" 1 => "L. Hansson" 2 => "I. Skoog" 3 => "D. Elmfeldt" 4 => "A. Hofman" 5 => "B. Olofsson" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/00004872-200305000-00011" "Revista" => array:6 [ "tituloSerie" => "J Hypertens" "fecha" => "2003" "volumen" => "21" "paginaInicial" => "875" "paginaFinal" => "886" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12714861" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0180" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "ALLHAT findings revisited in the context of subsequent analyses, other trials, and meta-analyses" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.T. Wright Jr." 1 => "J.L. Probstfield" 2 => "W.C. Cushman" 3 => "S.L. Pressel" 4 => "J.A. Cutler" 5 => "B.R. Davis" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1001/archinternmed.2009.60" "Revista" => array:6 [ "tituloSerie" => "Arch Intern Med" "fecha" => "2009" "volumen" => "169" "paginaInicial" => "832" "paginaFinal" => "842" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19433694" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0185" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Renal outcomes in high-risk hypertensive patients treated with an angiotensin-converting enzyme inhibitor or a calcium channel blocker vs. a diuretic: a report from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Rahman" 1 => "S. Pressel" 2 => "B.R. Davis" 3 => "C. Nwachuku" 4 => "J.T. Wright Jr." 5 => "P.K. Whelton" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1001/archinte.165.8.936" "Revista" => array:6 [ "tituloSerie" => "Arch Intern Med" "fecha" => "2005" "volumen" => "165" "paginaInicial" => "936" "paginaFinal" => "946" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15851647" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0190" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effect of telmisartan on renal outcomes: a randomized trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.F. Mann" 1 => "R.E. Schmieder" 2 => "L. Dyal" 3 => "M.J. McQueen" 4 => "H. Schumacher" 5 => "J. Pogue" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.7326/0003-4819-151-1-200907070-00122" "Revista" => array:6 [ "tituloSerie" => "Ann Intern Med" "fecha" => "2009" "volumen" => "151" "paginaInicial" => "1" "paginaFinal" => "10" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19451556" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0195" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Heart outcomes prevention evaluation study investigators" "autores" => array:1 [ 0 => array:2 [ "colaboracion" => "Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE substudy" "etal" => false ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Lancet" "fecha" => "2000" "volumen" => "355" "paginaInicial" => "253" "paginaFinal" => "259" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10675071" "web" => "Medline" ] ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0200" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "B.M. Brenner" 1 => "M.E. Cooper" 2 => "D. de Zeeuw" 3 => "W.F. Keane" 4 => "W.E. Mitch" 5 => "H.H. Parving" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa011161" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2001" "volumen" => "345" "paginaInicial" => "861" "paginaFinal" => "869" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11565518" "web" => "Medline" ] ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0205" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "E.J. Lewis" 1 => "L.G. Hunsicker" 2 => "W.R. Clarke" 3 => "T. Berl" 4 => "M.A. Pohl" 5 => "J.B. Lewis" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "N Engl J Med" "fecha" => "2001" "volumen" => "345" "paginaInicial" => "851" "paginaFinal" => "860" ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0210" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effect of blood pressure lowering and antihypertensive drug class on progression of hypertensive kidney disease: results from the AASK trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.T. Wright Jr." 1 => "G. Bakris" 2 => "T. Greene" 3 => "L.Y. Agodoa" 4 => "L.J. Appel" 5 => "J. Charleston" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "J Am Med Assoc" "fecha" => "2002" "volumen" => "288" "paginaInicial" => "2421" "paginaFinal" => "2431" ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0215" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The impact of stopping inhibitors of the renin–angiotensin system in patients with advanced chronic kidney disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "A. Ahmed" 1 => "N. Kamath" 2 => "M. El Kossi" 3 => "A. El Nahas" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/ndt/gfp511" "Revista" => array:6 [ "tituloSerie" => "Nephrol Dial Transplant" "fecha" => "2010" "volumen" => "25" "paginaInicial" => "3977" "paginaFinal" => "3982" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19820248" "web" => "Medline" ] ] ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib0220" "etiqueta" => "19" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Renal outcomes with telmisartan, ramipril, or both, in people at high vascular risk (the ONTARGET study): a multicentre, randomised, double-blind, controlled trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.F. Mann" 1 => "R.E. Schmieder" 2 => "M. McQueen" 3 => "L. Dyal" 4 => "H. Schumacher" 5 => "J. Pogue" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0140-6736(08)61236-2" "Revista" => array:6 [ "tituloSerie" => "Lancet" "fecha" => "2008" "volumen" => "372" "paginaInicial" => "547" "paginaFinal" => "553" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18707986" "web" => "Medline" ] ] ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib0225" "etiqueta" => "20" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Multicentre randomized controlled trial of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker withdrawal in advanced renaldisease: the STOP-ACEi trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S. Bhandari" 1 => "N. Ives" 2 => "E.A. Brettell" 3 => "M. Valente" 4 => "P. Cockwell" 5 => "P.S. Topham" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/ndt/gfv346" "Revista" => array:6 [ "tituloSerie" => "Nephrol Dial Transplant" "fecha" => "2016" "volumen" => "31" "paginaInicial" => "255" "paginaFinal" => "261" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26429974" "web" => "Medline" ] ] ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib0230" "etiqueta" => "21" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "S. Yusuf" 1 => "P. Sleight" 2 => "J. Pogue" 3 => "J. Bosch" 4 => "R. Davies" 5 => "G. Dagenais" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJM200001203420301" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2000" "volumen" => "342" "paginaInicial" => "145" "paginaFinal" => "153" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10639539" "web" => "Medline" ] ] ] ] ] ] ] ] 21 => array:3 [ "identificador" => "bib0235" "etiqueta" => "22" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Efficacy of perindopril in reduction of cardiovascular events among patients with stable coronary artery disease: randomised, double-blind, placebo-controlled, multicentre trial (the EUROPA study)" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "K.M. Fox" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/s0140-6736(03)14286-9" "Revista" => array:6 [ "tituloSerie" => "Lancet" "fecha" => "2003" "volumen" => "362" "paginaInicial" => "782" "paginaFinal" => "788" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/13678872" "web" => "Medline" ] ] ] ] ] ] ] ] 22 => array:3 [ "identificador" => "bib0240" "etiqueta" => "23" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "C.W. Yancy" 1 => "M. Jessup" 2 => "B. Bozkurt" 3 => "J. Butler" 4 => "D.E. Casey Jr." 5 => "M.M. Colvin" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1161/CIR.0000000000000509" "Revista" => array:6 [ "tituloSerie" => "Circulation" "fecha" => "2017" "volumen" => "136" "paginaInicial" => "e137" "paginaFinal" => "e161" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28455343" "web" => "Medline" ] ] ] ] ] ] ] ] 23 => array:3 [ "identificador" => "bib0245" "etiqueta" => "24" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Elevated relative mortality risk with mild-to-moderate chronic kidney disease decreases with age" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "N.T. Raymond" 1 => "D. Zehnder" 2 => "S.C. Smith" 3 => "J.A. Stinson" 4 => "H. Lehnert" 5 => "R.M. Higgins" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/ndt/gfm396" "Revista" => array:6 [ "tituloSerie" => "Nephrol Dial Transplant" "fecha" => "2007" "volumen" => "22" "paginaInicial" => "3214" "paginaFinal" => "3220" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17631511" "web" => "Medline" ] ] ] ] ] ] ] ] 24 => array:3 [ "identificador" => "bib0250" "etiqueta" => "25" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Use of renin–angiotensin system blockade in advanced CKD: an NKF-KDOQI controversies report" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M.R. Weir" 1 => "J.I. Lakkis" 2 => "B. Jaar" 3 => "M.V. Rocco" 4 => "M.J. Choi" 5 => "H.J. Kramer" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1053/j.ajkd.2018.06.010" "Revista" => array:6 [ "tituloSerie" => "Am J Kidney Dis" "fecha" => "2018" "volumen" => "72" "paginaInicial" => "873" "paginaFinal" => "884" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30201547" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/18891837/0000003700000003/v1_202006200856/S1889183720300271/v1_202006200856/en/main.assets" "Apartado" => array:4 [ "identificador" => "9105" "tipo" => "SECCION" "es" => array:2 [ "titulo" => "Originales" "idiomaDefecto" => true ] "idiomaDefecto" => "es" ] "PDF" => "https://static.elsevier.es/multimedia/18891837/0000003700000003/v1_202006200856/S1889183720300271/v1_202006200856/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1889183720300271?idApp=UINPBA00004N"]

Estadísticas

Original article

The effect of renin–angiotensin–aldosterone system blockers on the progression of chronic kidney disease in hypertensive elderly patients without proteinuria: PROERCAN study. Rationale and design

Efecto de los bloqueantes del sistema renina-angiotensina-aldosterona en la progresión de la enfermedad renal crónica en pacientes añosos sin proteinuria: ensayo clínico PROERCAN. Diseño y justificación del estudio

A.M. García-Prietoa,

Autor para correspondencia

anamgarciaprieto@gmail.com

Corresponding author.

, Ú. Verdallesa, A.P. de Joséa, E. Verdea, D. Arroyoa, I. Aragoncilloa, T. Linaresa, D. Barbieria, M. Goicoecheaa,b

a Servicio Nefrología Hospital General Universitario Gregorio Marañón, Calle Doctor Esquerdo 46, 28007 Madrid, Spain

b Spanish Research Network (REDINREN), Madrid, Spain

Leído

117

Veces
se ha leído el artículo

101

Total PDF

Total HTML

Compartir estadísticas

 array:23 [
  "pii" => "S1889183720300271"
  "issn" => "18891837"
  "doi" => "10.1016/j.hipert.2020.02.005"
  "estado" => "S300"
  "fechaPublicacion" => "2020-07-01"
  "aid" => "411"
  "copyright" => "SEH&#45;LELHA"
  "copyrightAnyo" => "2020"
  "documento" => "article"
  "crossmark" => 1
  "subdocumento" => "fla"
  "cita" => "Hipertens Riesgo Vasc. 2020;37:101-7"
  "abierto" => array:3 [
    "ES" => false
    "ES2" => false
    "LATM" => false
  ]
  "gratuito" => false
  "lecturas" => array:1 [
    "total" => 0
  ]
  "itemSiguiente" => array:18 [
    "pii" => "S1889183720300325"
    "issn" => "18891837"
    "doi" => "10.1016/j.hipert.2020.03.001"
    "estado" => "S300"
    "fechaPublicacion" => "2020-07-01"
    "aid" => "413"
    "copyright" => "SEH&#45;LELHA"
    "documento" => "article"
    "crossmark" => 1
    "subdocumento" => "fla"
    "cita" => "Hipertens Riesgo Vasc. 2020;37:108-14"
    "abierto" => array:3 [
      "ES" => false
      "ES2" => false
      "LATM" => false
    ]
    "gratuito" => false
    "lecturas" => array:1 [
      "total" => 0
    ]
    "es" => array:13 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">ORIGINAL</span>"
      "titulo" => "Asociaci&#243;n de des&#243;rdenes auton&#243;micos con aterosclerosis subcl&#237;nica"
      "tienePdf" => "es"
      "tieneTextoCompleto" => "es"
      "tieneResumen" => array:2 [
        0 => "es"
        1 => "en"
      ]
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "108"
          "paginaFinal" => "114"
        ]
      ]
      "titulosAlternativos" => array:1 [
        "en" => array:1 [
          "titulo" => "Association between autonomic disorders and subclinical atherosclerosis"
        ]
      ]
      "contieneResumen" => array:2 [
        "es" => true
        "en" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "es" => true
      ]
      "contienePdf" => array:1 [
        "es" => true
      ]
      "resumenGrafico" => array:2 [
        "original" => 0
        "multimedia" => array:7 [
          "identificador" => "fig0005"
          "etiqueta" => "Figura 1"
          "tipo" => "MULTIMEDIAFIGURA"
          "mostrarFloat" => true
          "mostrarDisplay" => false
          "figura" => array:1 [
            0 => array:4 [
              "imagen" => "gr1.jpeg"
              "Alto" => 967
              "Ancho" => 1616
              "Tamanyo" => 58149
            ]
          ]
          "descripcion" => array:1 [
            "es" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Espectro de baja frecuencia seg&#250;n presencia o ausencia de ateromatosis carot&#237;dea&#46;</p> <p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">LFln&#58; 4&#44;92 ATE&#43;<span class="elsevierStyleHsp" style=""></span>vs&#46; 6&#44;22 en ATE&#8722;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;0001&#46;</p> <p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Los datos se expresan como logaritmo de baja frecuencia&#46;</p> <p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">ATE&#8722;&#58; individuos sin ateromatosis carot&#237;dea&#59; ATE&#43;&#58; individuos con ateromatosis carot&#237;dea&#59; LFln&#58; logaritmo de baja frecuencia&#46;</p>"
          ]
        ]
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "D&#46;S&#46; Mendo, S&#46;A&#46; Gonz&#225;lez, H&#46;A&#46; Bonaccorsi"
          "autores" => array:3 [
            0 => array:2 [
              "nombre" => "D&#46;S&#46;"
              "apellidos" => "Mendo"
            ]
            1 => array:2 [
              "nombre" => "S&#46;A&#46;"
              "apellidos" => "Gonz&#225;lez"
            ]
            2 => array:2 [
              "nombre" => "H&#46;A&#46;"
              "apellidos" => "Bonaccorsi"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "es"
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1889183720300325?idApp=UINPBA00004N"
    "url" => "/18891837/0000003700000003/v1_202006200856/S1889183720300325/v1_202006200856/es/main.assets"
  ]
  "itemAnterior" => array:17 [
    "pii" => "S1889183720300349"
    "issn" => "18891837"
    "doi" => "10.1016/j.hipert.2020.04.002"
    "estado" => "S300"
    "fechaPublicacion" => "2020-07-01"
    "aid" => "415"
    "documento" => "article"
    "crossmark" => 1
    "subdocumento" => "sco"
    "cita" => "Hipertens Riesgo Vasc. 2020;37:99-100"
    "abierto" => array:3 [
      "ES" => false
      "ES2" => false
      "LATM" => false
    ]
    "gratuito" => false
    "lecturas" => array:1 [
      "total" => 0
    ]
    "es" => array:10 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Editorial</span>"
      "titulo" => "Bloqueantes del sistema renina-angiotensina e infecci&#243;n por COVID-19"
      "tienePdf" => "es"
      "tieneTextoCompleto" => "es"
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "99"
          "paginaFinal" => "100"
        ]
      ]
      "titulosAlternativos" => array:1 [
        "en" => array:1 [
          "titulo" => "Renin-angiotensin system blockers and COVID-19 infection"
        ]
      ]
      "contieneTextoCompleto" => array:1 [
        "es" => true
      ]
      "contienePdf" => array:1 [
        "es" => true
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "L&#46;M&#46; Ruilope, J&#46;A&#46; Garcia Donaire, A&#46; de la Sierra"
          "autores" => array:3 [
            0 => array:2 [
              "nombre" => "L&#46;M&#46;"
              "apellidos" => "Ruilope"
            ]
            1 => array:2 [
              "nombre" => "J&#46;A&#46;"
              "apellidos" => "Garcia Donaire"
            ]
            2 => array:2 [
              "nombre" => "A&#46;"
              "apellidos" => "de la Sierra"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "es"
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1889183720300349?idApp=UINPBA00004N"
    "url" => "/18891837/0000003700000003/v1_202006200856/S1889183720300349/v1_202006200856/es/main.assets"
  ]
  "en" => array:19 [
    "idiomaDefecto" => true
    "cabecera" => "<span class="elsevierStyleTextfn">Original article</span>"
    "titulo" => "The effect of renin&#8211;angiotensin&#8211;aldosterone system blockers on the progression of chronic kidney disease in hypertensive elderly patients without proteinuria&#58; PROERCAN study&#46; Rationale and design"
    "tieneTextoCompleto" => true
    "paginas" => array:1 [
      0 => array:2 [
        "paginaInicial" => "101"
        "paginaFinal" => "107"
      ]
    ]
    "autores" => array:1 [
      0 => array:4 [
        "autoresLista" => "A&#46;M&#46; Garc&#237;a-Prieto, &#218;&#46; Verdalles, A&#46;P&#46; de Jos&#233;, E&#46; Verde, D&#46; Arroyo, I&#46; Aragoncillo, T&#46; Linares, D&#46; Barbieri, M&#46; Goicoechea"
        "autores" => array:9 [
          0 => array:4 [
            "nombre" => "A&#46;M&#46;"
            "apellidos" => "Garc&#237;a-Prieto"
            "email" => array:1 [
              0 => "anamgarciaprieto@gmail.com"
            ]
            "referencia" => array:2 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
              1 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">&#42;</span>"
                "identificador" => "cor0005"
              ]
            ]
          ]
          1 => array:3 [
            "nombre" => "&#218;&#46;"
            "apellidos" => "Verdalles"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
            ]
          ]
          2 => array:3 [
            "nombre" => "A&#46;P&#46;"
            "apellidos" => "de Jos&#233;"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
            ]
          ]
          3 => array:3 [
            "nombre" => "E&#46;"
            "apellidos" => "Verde"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
            ]
          ]
          4 => array:3 [
            "nombre" => "D&#46;"
            "apellidos" => "Arroyo"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
            ]
          ]
          5 => array:3 [
            "nombre" => "I&#46;"
            "apellidos" => "Aragoncillo"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
            ]
          ]
          6 => array:3 [
            "nombre" => "T&#46;"
            "apellidos" => "Linares"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
            ]
          ]
          7 => array:3 [
            "nombre" => "D&#46;"
            "apellidos" => "Barbieri"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
            ]
          ]
          8 => array:3 [
            "nombre" => "M&#46;"
            "apellidos" => "Goicoechea"
            "referencia" => array:2 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
              1 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">b</span>"
                "identificador" => "aff0010"
              ]
            ]
          ]
        ]
        "afiliaciones" => array:2 [
          0 => array:3 [
            "entidad" => "Servicio Nefrolog&#237;a Hospital General Universitario Gregorio Mara&#241;&#243;n&#44; Calle Doctor Esquerdo 46&#44; 28007 Madrid&#44; Spain"
            "etiqueta" => "a"
            "identificador" => "aff0005"
          ]
          1 => array:3 [
            "entidad" => "Spanish Research Network &#40;REDINREN&#41;&#44; Madrid&#44; Spain"
            "etiqueta" => "b"
            "identificador" => "aff0010"
          ]
        ]
        "correspondencia" => array:1 [
          0 => array:3 [
            "identificador" => "cor0005"
            "etiqueta" => "&#8270;"
            "correspondencia" => "Corresponding author&#46;"
          ]
        ]
      ]
    ]
    "titulosAlternativos" => array:1 [
      "es" => array:1 [
        "titulo" => "Efecto de los bloqueantes del sistema renina-angiotensina-aldosterona en la progresi&#243;n de la enfermedad renal cr&#243;nica en pacientes a&#241;osos sin proteinuria&#58; ensayo cl&#237;nico PROERCAN&#46; Dise&#241;o y justificaci&#243;n del estudio"
      ]
    ]
    "resumenGrafico" => array:2 [
      "original" => 0
      "multimedia" => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 2386
            "Ancho" => 2500
            "Tamanyo" => 339134
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Schema for PROERCAN trial&#46; CKD&#44; chronic kidney disease&#46; RAS&#44; renin&#8211;angiotensin-system&#46; ACEi&#44; angiotensin converting enzyme&#46; BP&#44; blood pressure&#46; Egfr&#44; estimated glomerular filtration rate&#46;</p>"
        ]
      ]
    ]
    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Introduction and rationale</span><p id="par0005" class="elsevierStylePara elsevierViewall">Given the increased life expectancy&#44; there is a rising prevalence of elderly patients with chronic diseases such as diabetes&#44; hypertension or chronic kidney disease &#40;CKD&#41;&#46; Whereas the prevalence of CKD is estimated to be 6&#8211;18&#37; worldwide&#44;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">1</span></a> it raises up to 23&#46;4&#8211;35&#46;8&#37; in patients over 65 years of age&#44; affecting 30&#37; of patients over 70 years old and almost 50&#37; over 85 years old&#46;<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">2&#44;3</span></a> Thus&#44; the spectrum of patients that attend the Nephrology outpatient clinics has significantly changed in the last years&#44; being now older and with a higher prevalence of vascular and interstitial nephropathies that are characterized by minimum proteinuria and slowly progressive CKD&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Blood pressure &#40;BP&#41; control is fundamental to the care of patients with CKD and is relevant at all stages of CKD regardless the underlying cause of renal disease&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">4</span></a> Renin&#8211;angiotensine&#8211;aldosterone system &#40;RAAS&#41; blockers have shown to be effective in controlling BP and proteinuria&#44; slowing the progression to end stage renal disease &#40;ESRD&#41; and reducing cardiovascular risk&#44;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">5</span></a> so they are the mainstream treatment of hypertension in CKD&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">4</span></a> However&#44; most of the randomized clinical trials &#40;RCTs&#41; that have shown RAAS blockers benefits have excluded elderly patients with CKD&#44;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">6</span></a> so there is a lack of evidence in this population&#46; There are some data available on their use in the elderly&#44; but they come from RCTs that were not designed to analyze kidney function as a main outcome&#44; and results are thus controversial&#46; In addition&#44; this population appears to be more susceptible to its adverse events&#44; such as hyperkalaemia&#44; hypotension or acute kidney failure&#46; Thus&#44; there is a lack of evidence on the effect of RAAS blockers on BP control and CKD progression in elderly patients&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">The aim of this study is to evaluate the impact of the administration of RAAS blockers in the progression of renal disease in elderly patients with CKD without proteinuria&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Materials and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Study design</span><p id="par0020" class="elsevierStylePara elsevierViewall">The PROERCAN &#40;PROgresi&#243;n de Enfermedad Renal Cr&#243;nica en ANcianos&#41; trial &#40;trial registration&#58; <a href="ctgov:NCT03195023">NCT03195023</a>&#41; is a multicenter&#44; open label&#44; randomized controlled clinical trial&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Recruitment</span><p id="par0025" class="elsevierStylePara elsevierViewall">Participants will be recruited from 2 renal units&#46; The study has been approved by the Institutional Ethics Committee &#40;with adherence to the Declaration of Helsinki&#41;&#44; an each participating patient will give informed consent before enrollment&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Inclusion and exclusion criteria</span><p id="par0030" class="elsevierStylePara elsevierViewall">Inclusion criteria are as follows&#58;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">-</span><p id="par0035" class="elsevierStylePara elsevierViewall">Aged<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>65 years&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">-</span><p id="par0040" class="elsevierStylePara elsevierViewall">Previous history of hypertension under any antihypertensive treatment&#58;<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">&#8226;</span><p id="par0045" class="elsevierStylePara elsevierViewall">Patients who have not received RAAS blockers during a 3 month period prior to inclusion could be directly included&#46;</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">&#8226;</span><p id="par0050" class="elsevierStylePara elsevierViewall">Patients who have received RAAS blockers in the 3 months prior to inclusion could be included after a one month washout period&#46;</p></li></ul></p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">-</span><p id="par0055" class="elsevierStylePara elsevierViewall">CKD stage 3 or 4 &#40;estimated glomerular filtration rate &#40;eGRF&#41; 15&#8211;60<span class="elsevierStyleHsp" style=""></span>ml&#47;min&#47;1&#46;73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>&#41; using the CKD-EPI &#40;Chronic Kidney Disease Epidemiology Collaboration&#41; equation with at least one year of specialist renal follow up&#46;</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">-</span><p id="par0060" class="elsevierStylePara elsevierViewall">Urinary albumin&#47;creatinine ratio &#40;UACR&#41;<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>30<span class="elsevierStyleHsp" style=""></span>mg&#47;g&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Exclusion criteria are as follows&#58;</p></li><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">-</span><p id="par0070" class="elsevierStylePara elsevierViewall">Diabetes mellitus</p></li><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">-</span><p id="par0075" class="elsevierStylePara elsevierViewall">Glomerular nephropathies</p></li><li class="elsevierStyleListItem" id="lsti0045"><span class="elsevierStyleLabel">-</span><p id="par0080" class="elsevierStylePara elsevierViewall">History of congestive heart failure or myocardial infarction</p></li><li class="elsevierStyleListItem" id="lsti0050"><span class="elsevierStyleLabel">-</span><p id="par0085" class="elsevierStylePara elsevierViewall">Resistant or uncontrolled hypertension &#40;BP<span class="elsevierStyleHsp" style=""></span>&#62;160&#47;100<span class="elsevierStyleHsp" style=""></span>mmHg&#41;</p></li><li class="elsevierStyleListItem" id="lsti0055"><span class="elsevierStyleLabel">-</span><p id="par0090" class="elsevierStylePara elsevierViewall">Solitary functioning kidney</p></li><li class="elsevierStyleListItem" id="lsti0060"><span class="elsevierStyleLabel">-</span><p id="par0095" class="elsevierStylePara elsevierViewall">Active malignant disease &#40;except skin cancer different from melanoma&#41;&#46; Patients can be included if they have been free of the disease for at least 5 years</p></li><li class="elsevierStyleListItem" id="lsti0065"><span class="elsevierStyleLabel">-</span><p id="par0100" class="elsevierStylePara elsevierViewall">Active inflammatory disease &#40;e&#46;g&#46; rheumatoid artritis&#44; systemic lupus erythematous&#44; Chron&#39;s disease&#44; etc&#46;&#41;</p></li><li class="elsevierStyleListItem" id="lsti0070"><span class="elsevierStyleLabel">-</span><p id="par0105" class="elsevierStylePara elsevierViewall">Cirrhosis</p></li><li class="elsevierStyleListItem" id="lsti0075"><span class="elsevierStyleLabel">-</span><p id="par0110" class="elsevierStylePara elsevierViewall">Allergy or intolerance to angiotensin converting enzyme inhibitors &#40;ACEi&#41; or calcium channel blockers &#40;CCB&#41;</p></li><li class="elsevierStyleListItem" id="lsti0080"><span class="elsevierStyleLabel">-</span><p id="par0115" class="elsevierStylePara elsevierViewall">Chronic infection from hepatitis B or C virus or human immunodeficiency virus</p></li><li class="elsevierStyleListItem" id="lsti0085"><span class="elsevierStyleLabel">-</span><p id="par0120" class="elsevierStylePara elsevierViewall">Immunosuppressive treatment during the 12 weeks prior to inclusion</p></li><li class="elsevierStyleListItem" id="lsti0090"><span class="elsevierStyleLabel">-</span><p id="par0125" class="elsevierStylePara elsevierViewall">Hospitalization during the 3 months prior to inclusion</p></li><li class="elsevierStyleListItem" id="lsti0095"><span class="elsevierStyleLabel">-</span><p id="par0130" class="elsevierStylePara elsevierViewall">Rapidly progressive chronic kidney disease defined as a fall in eGFR<span class="elsevierStyleHsp" style=""></span>&#62;5<span class="elsevierStyleHsp" style=""></span>ml&#47;min&#47;1&#46;73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span></p></li><li class="elsevierStyleListItem" id="lsti0100"><span class="elsevierStyleLabel">-</span><p id="par0135" class="elsevierStylePara elsevierViewall">Inability to provide informed consent</p></li><li class="elsevierStyleListItem" id="lsti0105"><span class="elsevierStyleLabel">-</span><p id="par0140" class="elsevierStylePara elsevierViewall">Inability to comply with the trial schedule and follow up&#46;</p></li></ul></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Study enrolment and randomization</span><p id="par0145" class="elsevierStylePara elsevierViewall">Following informed consent and completion of the baseline assessment&#44; patients will be randomized into the trial in a 1&#58;1 ratio to either receive ACEi or antihypertensive treatment without RAAS blockers&#46; Randomization will be provided by a computer-generated program using a minimization algorithm to ensure balance between the arms &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Study treatment</span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">ACEi arm</span><p id="par0150" class="elsevierStylePara elsevierViewall">Patients that were receiving an ACEi prior to inclusion can continue with their previous antihypertensive treatment after the washout period of one month&#46; Patients that were not receiving an ACEi will start receiving Lisinopril 20<span class="elsevierStyleHsp" style=""></span>mg a day that can be adjusted depending on BP control&#46; The reason to use lisinopril was based on its long half life that allows a daily dose&#44; thus facilitating compliance&#46; Any other antihypertensive treatment used in routine clinical practice can be added to control BP&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Non-ACEi arm</span><p id="par0155" class="elsevierStylePara elsevierViewall">Patients that were receiving an ACEi prior to inclusion will discontinue it and&#44; in order to compensate for the loss of antihypertensive activity&#44; treatment with Amlodipine 10<span class="elsevierStyleHsp" style=""></span>mg a day or Lercanidipine 20<span class="elsevierStyleHsp" style=""></span>mg a day &#40;depending on the presence of edema&#41; will be commenced&#46; Any other antihypertensive treatment used in routine clinical practice can be added to achieve BP control&#46; Patients that were not receiving an ACEi prior to inclusion can continue with their previous antihypertensive treatment&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Both treatment groups</span><p id="par0160" class="elsevierStylePara elsevierViewall">In both groups&#44; BP will be controlled to the target pressure outlined in the European Society of Cardiology-European Society of Hypertension &#40;ESC-ESH&#41; guideline<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">7</span></a> of 140&#47;90<span class="elsevierStyleHsp" style=""></span>mmHg&#46;</p></span></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Blinding</span><p id="par0165" class="elsevierStylePara elsevierViewall">Trial treatment will be open label&#44; due to the practical difficulties and costs associated with using placebo in a trial of drug withdrawal&#46; However&#44; the primary outcome is an objective laboratory measure that reduces the need for blinding&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Assessments</span><p id="par0170" class="elsevierStylePara elsevierViewall">Participants will be assessed at month 1&#44; 3&#44; 6&#44; 12&#44; 18&#44; 24 and 36 in the patient&#39;s routine outpatient clinic visit&#46; Demographic data and detailed previous medical history will be collected at baseline as well as BP and decline in eGFR in the 12 month period prior to inclusion&#46; BP will be recorded at each visit&#44; and changes to antihypertensive and other concomitant medication will be recorded&#46; Urine and blood samples will be taken at baseline and in each visit &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Primary outcome</span><p id="par0175" class="elsevierStylePara elsevierViewall">The primary outcome measure is difference in renal function measured using the CKD-EPI eGFR at the 3 years of follow up&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Secondary outcome</span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Renal events</span><p id="par0180" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0110"><span class="elsevierStyleLabel">&#8226;</span><p id="par0185" class="elsevierStylePara elsevierViewall">Number of patients with an increase of<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>50&#37; decline in eGFR or starting renal replacement therapy&#46;</p></li><li class="elsevierStyleListItem" id="lsti0115"><span class="elsevierStyleLabel">&#8226;</span><p id="par0190" class="elsevierStylePara elsevierViewall">Time to ESRD&#46;</p></li></ul></p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Clinical events</span><p id="par0195" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0020"><li class="elsevierStyleListItem" id="lsti0120"><span class="elsevierStyleLabel">&#8226;</span><p id="par0200" class="elsevierStylePara elsevierViewall">BP control&#58; number of patients with controlled office BP &#40;defined as<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>140&#47;90<span class="elsevierStyleHsp" style=""></span>mmHg&#41;&#46;</p></li></ul></p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Laboratory measures</span><p id="par0205" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0025"><li class="elsevierStyleListItem" id="lsti0125"><span class="elsevierStyleLabel">&#8226;</span><p id="par0210" class="elsevierStylePara elsevierViewall">UACR&#58;<ul class="elsevierStyleList" id="lis0030"><li class="elsevierStyleListItem" id="lsti0130"><span class="elsevierStyleLabel">&#8728;</span><p id="par0215" class="elsevierStylePara elsevierViewall">Number of patients with normo&#44; micro and macroalbuminuria&#46;</p></li><li class="elsevierStyleListItem" id="lsti0135"><span class="elsevierStyleLabel">&#8728;</span><p id="par0220" class="elsevierStylePara elsevierViewall">Number of patients with normoalbuminuria that develope micro or macroalbuminuria during follow up&#46;</p></li></ul></p></li><li class="elsevierStyleListItem" id="lsti0140"><span class="elsevierStyleLabel">&#8226;</span><p id="par0225" class="elsevierStylePara elsevierViewall">Total serum CO<span class="elsevierStyleInf">2</span> levels&#46;</p></li></ul></p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Safety</span><p id="par0230" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0035"><li class="elsevierStyleListItem" id="lsti0145"><span class="elsevierStyleLabel">&#8226;</span><p id="par0235" class="elsevierStylePara elsevierViewall">Number of hyperkalemic &#40;<span class="elsevierStyleItalic">K</span><span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>5&#46;5<span class="elsevierStyleHsp" style=""></span>mmol&#47;l&#41; episodes&#46;</p></li><li class="elsevierStyleListItem" id="lsti0150"><span class="elsevierStyleLabel">&#8226;</span><p id="par0240" class="elsevierStylePara elsevierViewall">Number and type of cardiovascular events&#46;</p></li><li class="elsevierStyleListItem" id="lsti0155"><span class="elsevierStyleLabel">&#8226;</span><p id="par0245" class="elsevierStylePara elsevierViewall">Global and cardiovascular mortality&#46;</p></li></ul></p><p id="par0250" class="elsevierStylePara elsevierViewall">Serious adverse events will be monitored and reported within a 24<span class="elsevierStyleHsp" style=""></span>h period&#46; Those that will end in patient discontinuation will be&#58; allergy to any drug used in the trial and hyperkalemia<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>7<span class="elsevierStyleHsp" style=""></span>mmol&#47;l&#46;</p></span></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Statistical considerations</span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">Sample size</span><p id="par0255" class="elsevierStylePara elsevierViewall">The absence of studies in elderly patients with CKD stages 3 and 4 leads us to use other studies performed by our group to estimate sample size&#46; In our study about the effect of allopurinol on CKD progression<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">8</span></a> that included 113 patients with CKD 3 and 4 with a follow up period of 24 months&#44; the eGFR fall a mean of 4<span class="elsevierStyleHsp" style=""></span>ml&#47;min&#47;1&#46;73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span> in the control group&#44; that is 2<span class="elsevierStyleHsp" style=""></span>ml&#47;min&#47;1&#46;73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span> per year&#46; Almost 80&#37; of those patients were receiving RAAS blockers&#46; Thus&#44; with a mean follow up of 3 years we must detect a difference of 6<span class="elsevierStyleHsp" style=""></span>ml&#47;min&#47;1&#46;73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span> between both groups&#46;</p><p id="par0260" class="elsevierStylePara elsevierViewall">To estimate a minimum relevant difference between groups of 6<span class="elsevierStyleHsp" style=""></span>ml&#47;min&#47;1&#46;73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span> with 80&#37; power and alpha<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;05 &#40;using a two-sample <span class="elsevierStyleItalic">t</span>-test&#41;&#44; a total of 110 will need to be recruited &#40;this includes allowance for 20&#37; dropout&#41;&#46;</p></span><span id="sec0105" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0160">Statistical analysis</span><p id="par0265" class="elsevierStylePara elsevierViewall">All analysis will be based on the intention to treat principle&#44; and a <span class="elsevierStyleItalic">p</span> value of<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05 will be considered statistically significant&#46; Variables&#8217; distribution will be analyzed using the Kolmogorov&#8211;Smirnov test&#46; The primary outcome is eGFR at 3 years&#46; These data will be summarized using means and standard deviations&#44; with differences in means and 95&#37; confidence intervals &#40;CIs&#41; reported&#46; The two groups will be compared at 3 years using a two-sample <span class="elsevierStyleItalic">t</span> test&#46; Continuous secondary outcome measures &#40;e&#46;g&#46; BP&#44; UACR&#44; etc&#46;&#41; will be analyzed in the same way as the primary outcome&#46; Categorical &#40;dichotomous&#41; outcome measures will compare the propotion of participants and percentages using a <span class="elsevierStyleItalic">&#967;</span><span class="elsevierStyleSup">2</span> test&#44; with relative risks and 95&#37; CIs reported&#46; Time to event outcomes will be analyzed using survival analysis and log-rank methods&#46; Kaplan&#8211;Meier survival curves will be constructed for visual presentation of time-to-event comparisons&#46; Treatment effects will be expressed as hazard ratios with 95&#37; CIs&#46; Multivariate regression model will be used to analyze variables that have an impact on CKD progression&#44; including those that result statistically significant in the univariate model&#46; Uni and multivariate Cox regression model will analyze variables related to higher cardiovascular risk and mortality&#46;</p></span></span><span id="sec0110" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0165">Regulatory aspects</span><p id="par0270" class="elsevierStylePara elsevierViewall">Written informed consent will be provided by all patients prior to randomization&#46; The study was conducted according to the Declaration of Helsinki&#46;</p></span><span id="sec0115" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0170">Ethical committee approval</span><p id="par0275" class="elsevierStylePara elsevierViewall">Ethical approval for PROERCAN01 was granted by local ethical committee &#40;Comit&#233; &#201;tico de Investigaci&#243;n Cl&#237;nica Hospital General Universitario Gregorio Mara&#241;&#243;n&#41; on 24 June 2015&#46;</p></span></span><span id="sec0120" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0175">Discussion</span><p id="par0280" class="elsevierStylePara elsevierViewall">BP control is fundamental to the care of patients with CKD and is relevant at all stages of renal disease&#46; RAAS blockers have shown to be effective not only in BP control but also in reducing proteinuria and slowing CKD progression&#46; However&#44; evidence to recommend RAAS blockers in elderly patients with CKD without proteinuria is lacking&#46; The primary outcome of our study is to evaluate the impact of RAAS blockers in CKD progression in elderly patients without proteinuria&#46;</p><p id="par0285" class="elsevierStylePara elsevierViewall">In elderly patients results&#44; obtained with RAAS blockers are similar in terms of kidney function when compared to other antihypertensive drugs&#44; and positive results have only been shown when some subgroups have been analyzed&#46; The Hypertension in the Very elderly Trial &#40;HYVET&#41;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">9</span></a> investigated the effect of active treatment on stroke incidence in hypertensive patients over the age of 80 years&#46; Secondary end-points included kidney function&#44; cardiovascular mortality and morbidity&#46; A total of 3845 patients were randomized to receive treatment with indapamide and&#47;or perindopril or placebo&#46; Indapamide treatment&#44; with or without perindopril&#44; was associated with better BP control and a 30&#37; reduction in the incidence of stroke&#46; Despite this benefit in stroke prevention in the treatment group&#44; there were no differences in renal events between patients who received an ACEi or not&#46; The Study on Cognition and Prognosis in the Elderly &#40;SCOPE&#41;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">10</span></a> was designed to assess whether RAAS blockers confer a reduction in cardiovascular events&#44; cognitive decline and dementia&#46; It included 4964 hypertensive elderly patients who were randomized to receive candesartan or placebo&#46; Treatment with candesartan was associated with a modest&#44; statistically non-significant&#44; reduction in major cardiovascular events and with a marked reduction in non-fatal stroke&#46; There were no differences in creatinine levels and CKD progression between groups&#46; Wright et al&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">11</span></a> performed a secondary analysis of elderly patients included in the Antihypertensive and Lipid-lowering treatment to prevent Heart Attack Trial &#40;ALLHAT&#41;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">12</span></a> and they found no benefit of lisinopril versus clortalidone in the prevention of CKD&#46; The Effect of Telmisartan on Renal Outcomes &#40;TRASCEND&#41; study<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">13</span></a> examined the effect of telmisartan versus placebo on kidney function&#46; In this study&#44; 5926 patients with diabetes or ischemic heart disease were randomized&#44; with a mean age of 66&#46;9 years&#46; Patients with creatinine<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>3<span class="elsevierStyleHsp" style=""></span>mg&#47;dl or macroalbuminuria were excluded&#46; Mean baseline creatinine was 1<span class="elsevierStyleHsp" style=""></span>mg&#47;dl and 10&#37; had microalbuminuria&#46; They found no statistically significant differences on renal events between groups&#46; Thus&#44; so far&#44; no data have been published about the beneficial effect of RAAS blockers in elderly patients with CKD&#46;</p><p id="par0290" class="elsevierStylePara elsevierViewall">In addition&#44; most of the RCTs that have shown RAAS blockers benefit on kidney function include patients with diabetes and proteinuria&#46;<a class="elsevierStyleCrossRefs" href="#bib0195"><span class="elsevierStyleSup">14&#8211;16</span></a> An exception was the African American Study of Kidney disease &#40;AASK&#41;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">17</span></a> that included 1029 african-american patients with non diabetic&#44; non proteinuric vascular nephropathy&#46; It showed a possible beneficial effect of ACEi treatment in slowing eGFR decline&#46; However&#44; patients included in this RCT were young &#40;mean age of 52 years&#41;&#46; Thus&#44; there is not enough evidence to support the use of RAAS blockers to slow CKD progression in patients without diabetes and proteinuria&#46; This is especially controversial in the elderly that tend to be more susceptible to RAAS blockers adverse events &#40;e&#46;g&#46; hyperkalaemia&#44; hypotension or acute kidney failure&#41;&#46; Ahmed et al&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">18</span></a> described the impact of RAAS blockers withdrawal in elderly patients &#40;mean age of 73&#46;3 years&#41; with advanced CKD that resulted in an improvement of eGFR from 16&#46;38<span class="elsevierStyleHsp" style=""></span>ml&#47;min&#47;m<span class="elsevierStyleSup">2</span> to 26&#46;6<span class="elsevierStyleHsp" style=""></span>ml&#47;min&#47;m<span class="elsevierStyleSup">2</span> over a 12 month period&#46; They suggested that RAAS blockers contribute to progression of advanced CKD in the elderly&#46; The Renal Outcomes with Telmisartan&#44; Ramipril&#44; or both&#44; in people at high vascular risk &#40;ONTARGET&#41;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">19</span></a> trial randomized 25&#44;620 patients to receive telmisartan&#44; ramipril or their combination to evaluate the impact on renal function&#46; A total of 6420 patients had an eGFR<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>60<span class="elsevierStyleHsp" style=""></span>ml&#47;min&#47;m<span class="elsevierStyleSup">2</span>&#44; with a mean age of 55 years&#46; Even though the patients treated with the combination had higher reduction of proteinuria&#44; the risk of CKD progression and hyperkalaemia raised compared to patients receiving monotherapy&#46; In this way&#44; there is an ongoing RCT called STOP-ACEi<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">20</span></a> designed to evaluate whether the discontinuation of RAAS blockers improves or stabilizes renal function in patients with advanced progressive CKD and diabetes mellitus&#46; 410 patients with advanced &#40;stages 4 and 5&#41; CKD that are currently receiving RAAS blockers will be included&#46; Patients will be randomly assigned in 1&#58;1 fashion to either discontinue the current RAAS regimen or continue treatment for 3 years&#46; Results are expected to be available by 2022&#46; These data suggest that discontinuing RAAS inhibitors in advanced CKD can be beneficial in CKD progression but no data have been published so far about the role of RAAS blockers in the elderly patients with less severe degrees of CKD without albuminuria&#46;</p><p id="par0295" class="elsevierStylePara elsevierViewall">In terms of cardiovascular risk&#44; ACEi have shown to reduce cardiovascular mortality in several RCTs like the MICRovascular Outcome in arm of the Heart Outcomes Prevention Evaluation study &#40;MICRO-HOPE&#41;<a class="elsevierStyleCrossRefs" href="#bib0190"><span class="elsevierStyleSup">13&#44;21</span></a> or the European Trial on Reduction of Cardiac Events with Perindopril in Stable Coronary Artery Disease &#40;EUROPA&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">22</span></a> that were performed in high cardiovascular risk patients&#46; However&#44; ACEi have not proved to reduce cardiovascular risk in patients without ischemic heart disease except for their effect on BP control and&#44; secondary&#44; on the incidence of non-fatal stroke as previously mentioned&#46;<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">9&#44;10</span></a> Moreover&#44; although CKD is considered as a high cardiovascular risk condition by the American Heart Association&#44;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">23</span></a> this statement is less strong in the elderly&#46; This is due to a relative risk of mortality and cardiovascular events among patients with CKD&#44; that increases until a certain age&#44; from which it stabilizes&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">24</span></a> Accordingly&#44; RAAS blockers benefit on cardiovascular risk in elderly patients with CKD must still to be confirmed&#46; In fact&#44; a National Kidney Foundation-Kidney Disease Global Outcomes &#40;NKF-KDIGO&#41; report has been recently published encouraging investigators to research in this field&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">25</span></a></p><p id="par0300" class="elsevierStylePara elsevierViewall">The result of our RCT will provide evidence on whether the discontinuation of RAAS blockers is beneficial to renal function and improves other important parameter including laboratory and clinical outcomes without causing an increase in cardiovascular events&#46; It is&#44; therefore&#44; hoped that this pivotal study can provide new findings to allow future consideration in the treatment of hypertension in elderly patients with CKD without proteinuria&#46;</p><span id="sec0125" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0180">Trial status</span><p id="par0305" class="elsevierStylePara elsevierViewall">PROERCAN opened recruitment on June 2015&#44; and the first patient was recruited on September 2015&#46; As of January 2020&#44; 79 patients &#40;72&#37;&#41; were recruited into the study&#46; Recruitment is still ongoing and is expected to be completed by July 2020&#46;</p></span></span><span id="sec0130" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0185">Funding</span><p id="par0310" class="elsevierStylePara elsevierViewall">None&#46;</p></span><span id="sec0135" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0190">Conflict of interest</span><p id="par0315" class="elsevierStylePara elsevierViewall">None to declare&#46;</p></span></span>"
    "textoCompletoSecciones" => array:1 [
      "secciones" => array:11 [
        0 => array:3 [
          "identificador" => "xres1351902"
          "titulo" => "Abstract"
          "secciones" => array:3 [
            0 => array:2 [
              "identificador" => "abst0005"
              "titulo" => "Introduction"
            ]
            1 => array:2 [
              "identificador" => "abst0010"
              "titulo" => "Materials and methods"
            ]
            2 => array:2 [
              "identificador" => "abst0015"
              "titulo" => "Results and conclusions"
            ]
          ]
        ]
        1 => array:2 [
          "identificador" => "xpalclavsec1243201"
          "titulo" => "Keywords"
        ]
        2 => array:2 [
          "identificador" => "xpalclavsec1243200"
          "titulo" => "Abbreviations"
        ]
        3 => array:3 [
          "identificador" => "xres1351903"
          "titulo" => "Resumen"
          "secciones" => array:3 [
            0 => array:2 [
              "identificador" => "abst0020"
              "titulo" => "Introducci&#243;n"
            ]
            1 => array:2 [
              "identificador" => "abst0025"
              "titulo" => "Material y m&#233;todos"
            ]
            2 => array:2 [
              "identificador" => "abst0030"
              "titulo" => "Resultados y conclusi&#243;n"
            ]
          ]
        ]
        4 => array:2 [
          "identificador" => "xpalclavsec1243202"
          "titulo" => "Palabras clave"
        ]
        5 => array:2 [
          "identificador" => "sec0005"
          "titulo" => "Introduction and rationale"
        ]
        6 => array:3 [
          "identificador" => "sec0010"
          "titulo" => "Materials and methods"
          "secciones" => array:12 [
            0 => array:2 [
              "identificador" => "sec0015"
              "titulo" => "Study design"
            ]
            1 => array:2 [
              "identificador" => "sec0020"
              "titulo" => "Recruitment"
            ]
            2 => array:2 [
              "identificador" => "sec0025"
              "titulo" => "Inclusion and exclusion criteria"
            ]
            3 => array:2 [
              "identificador" => "sec0030"
              "titulo" => "Study enrolment and randomization"
            ]
            4 => array:3 [
              "identificador" => "sec0035"
              "titulo" => "Study treatment"
              "secciones" => array:3 [
                0 => array:2 [
                  "identificador" => "sec0040"
                  "titulo" => "ACEi arm"
                ]
                1 => array:2 [
                  "identificador" => "sec0045"
                  "titulo" => "Non-ACEi arm"
                ]
                2 => array:2 [
                  "identificador" => "sec0050"
                  "titulo" => "Both treatment groups"
                ]
              ]
            ]
            5 => array:2 [
              "identificador" => "sec0055"
              "titulo" => "Blinding"
            ]
            6 => array:2 [
              "identificador" => "sec0060"
              "titulo" => "Assessments"
            ]
            7 => array:2 [
              "identificador" => "sec0065"
              "titulo" => "Primary outcome"
            ]
            8 => array:3 [
              "identificador" => "sec0070"
              "titulo" => "Secondary outcome"
              "secciones" => array:4 [
                0 => array:2 [
                  "identificador" => "sec0075"
                  "titulo" => "Renal events"
                ]
                1 => array:2 [
                  "identificador" => "sec0080"
                  "titulo" => "Clinical events"
                ]
                2 => array:2 [
                  "identificador" => "sec0085"
                  "titulo" => "Laboratory measures"
                ]
                3 => array:2 [
                  "identificador" => "sec0090"
                  "titulo" => "Safety"
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "sec0095"
              "titulo" => "Statistical considerations"
              "secciones" => array:2 [
                0 => array:2 [
                  "identificador" => "sec0100"
                  "titulo" => "Sample size"
                ]
                1 => array:2 [
                  "identificador" => "sec0105"
                  "titulo" => "Statistical analysis"
                ]
              ]
            ]
            10 => array:2 [
              "identificador" => "sec0110"
              "titulo" => "Regulatory aspects"
            ]
            11 => array:2 [
              "identificador" => "sec0115"
              "titulo" => "Ethical committee approval"
            ]
          ]
        ]
        7 => array:3 [
          "identificador" => "sec0120"
          "titulo" => "Discussion"
          "secciones" => array:1 [
            0 => array:2 [
              "identificador" => "sec0125"
              "titulo" => "Trial status"
            ]
          ]
        ]
        8 => array:2 [
          "identificador" => "sec0130"
          "titulo" => "Funding"
        ]
        9 => array:2 [
          "identificador" => "sec0135"
          "titulo" => "Conflict of interest"
        ]
        10 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2020-01-23"
    "fechaAceptado" => "2020-02-20"
    "PalabrasClave" => array:2 [
      "en" => array:2 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec1243201"
          "palabras" => array:5 [
            0 => "Albuminuria"
            1 => "Chronic kidney disease"
            2 => "Elderly"
            3 => "Hypertension"
            4 => "Renin&#8211;angiotensin-system"
          ]
        ]
        1 => array:4 [
          "clase" => "abr"
          "titulo" => "Abbreviations"
          "identificador" => "xpalclavsec1243200"
          "palabras" => array:9 [
            0 => "ACEi"
            1 => "BP"
            2 => "CCB"
            3 => "CKD"
            4 => "eGFR"
            5 => "ESRD"
            6 => "RAAS"
            7 => "RCT"
            8 => "UACR"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec1243202"
          "palabras" => array:5 [
            0 => "Albuminuria"
            1 => "Enfermedad renal cr&#243;nica"
            2 => "Ancianos"
            3 => "Hipertensi&#243;n"
            4 => "Sistema renina-angiotensina"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Blood pressure &#40;BP&#41; control is fundamental to the care of patients with chronic kidney disease &#40;CKD&#41;&#44; and is relevant at all stages of CKD&#46; Renin&#8211;angiotensin&#8211;aldosterone system &#40;RAAS&#41; blockers have shown to be effective&#44; not only in BP control but also in reducing proteinuria and slowing CKD progression&#46; However&#44; there is a lack of evidence for recommending RAAS blockers in elderly patients with CKD without proteinuria&#46; The primary outcome of the present study is to evaluate the impact of RAAS blockers on CKD progression in elderly patients without proteinuria&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Materials and methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">The PROERCAN trial &#40;trial registration&#44; <span class="elsevierStyleInterRef" id="intr0005" href="ctgov:NCT03195023">NCT03195023</span>&#41; is a multicentre open-label&#44; randomized controlled clinical trial with 110 participants over 65 years-old with hypertension and CKD stages 3&#8211;4 without proteinuria&#46; Patients will be randomized in a 1&#58;1 ratio to either receive RAAS blockers or other antihypertensive drugs&#44; and will be followed up for three years&#46; Primary outcome is the estimated glomerular filtration rate &#40;eGFR&#41; decline at 3 years&#46; Secondary outcomes include BP control&#44; renal and cardiovascular events&#44; and mortality&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results and conclusions</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">The design of this trial is presented here&#46; The results will show if antihypertensive treatment with RAAS blockers has an impact on CKD progression in elderly patients without proteinuria&#46; Any differences in BP control&#44; cardiovascular events&#44; and mortality with each antihypertensive treatment will be also clarified&#46;</p></span>"
        "secciones" => array:3 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Introduction"
          ]
          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Materials and methods"
          ]
          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Results and conclusions"
          ]
        ]
      ]
      "es" => array:3 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Introducci&#243;n</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">El control de la presi&#243;n arterial &#40;PA&#41; es fundamental para los pacientes con enfermedad renal cr&#243;nica &#40;ERC&#41; y es relevante en todos los estadios de ERC&#46; Los bloqueantes del sistema renina-angiotensina-aldosterona &#40;BSRAA&#41; han demostrado su efectividad no solo en el control de la PA sino tambi&#233;n en la reducci&#243;n de la proteinuria y de la progresi&#243;n de la ERC&#46; Sin embargo&#44; no existe evidencia para recomendar el uso de BSRAA en pacientes a&#241;osos con ERC sin proteinuria&#46; El objetivo principal del estudio es evaluar el impacto de los BSRAA en la progresi&#243;n de ERC en pacientes a&#241;osos sin proteinuria&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Material y m&#233;todos</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">El estudio PROERCAN &#40;<span class="elsevierStyleInterRef" id="intr0010" href="ctgov:NCT03195023">NCT03195023</span>&#41; es un ensayo cl&#237;nico multic&#233;ntrico&#44; abierto&#44; aleatorizado de 110 pacientes hipertensos&#44; mayores de 65<span class="elsevierStyleHsp" style=""></span>a&#241;os con ERC estadios<span class="elsevierStyleHsp" style=""></span>3 y<span class="elsevierStyleHsp" style=""></span>4 sin proteinuria&#46; Los pacientes son aleatorizados 1&#58;1 a recibir tratamiento con BSRAA u otros antihipertensivos y el seguimiento ser&#225; de 3<span class="elsevierStyleHsp" style=""></span>a&#241;os&#46; La variable principal es el descenso del filtrado glomerular estimado durante el tiempo de seguimiento&#46; Las variables secundarias incluyen las cifras de PA&#44; eventos renales y cardiovasculares y mortalidad&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Resultados y conclusi&#243;n</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">El dise&#241;o del ensayo cl&#237;nico se desarrolla en el presente art&#237;culo&#46; Los resultados determinar&#225;n si el tratamiento antihipertensivo con BSRAA tiene un impacto en la progresi&#243;n de la ERC en pacientes a&#241;osos sin proteinuria&#46; As&#237; mismo&#44; se aclarar&#225;n las diferencias en el control de la PA&#44; los eventos cardiovasculares y la mortalidad con los distintos tratamientos antihipertensivos&#46;</p></span>"
        "secciones" => array:3 [
          0 => array:2 [
            "identificador" => "abst0020"
            "titulo" => "Introducci&#243;n"
          ]
          1 => array:2 [
            "identificador" => "abst0025"
            "titulo" => "Material y m&#233;todos"
          ]
          2 => array:2 [
            "identificador" => "abst0030"
            "titulo" => "Resultados y conclusi&#243;n"
          ]
        ]
      ]
    ]
    "multimedia" => array:2 [
      0 => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 2386
            "Ancho" => 2500
            "Tamanyo" => 339134
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Schema for PROERCAN trial&#46; CKD&#44; chronic kidney disease&#46; RAS&#44; renin&#8211;angiotensin-system&#46; ACEi&#44; angiotensin converting enzyme&#46; BP&#44; blood pressure&#46; Egfr&#44; estimated glomerular filtration rate&#46;</p>"
        ]
      ]
      1 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at1"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">eGFR&#58; estimated glomerular filtration rate&#59; UACR&#58; urinary albumin&#47;creatinine ratio&#59; BP&#58; blood pressure&#59; RAAS&#58; renin&#8211;angiotensin&#8211;aldosterone system&#59; SAE&#58; seriour adverse events&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Visit&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Procedures&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8722;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sign informed consent&#46;Retrospective data collection &#40;12 month prior to inclusion&#41;&#58; potassium&#44; creatinine&#44; eGFR&#44; UACR&#44; BP&#46;If under RAAS blocker treatment&#58; 1 month wash out period&#46; If not&#44; patient can be redirected to visit 0&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0First visit&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Randomization&#46;Detailed medical history including medication&#46;Physical examination including BP&#46;Blood and urinary samples&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1Month 1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Detailed medical history including medication&#44; SAE and other clincial events&#46;Physical examination including BP&#46;Blood and urinary samples&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2Month 3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Detailed medical history including medication&#44; SAE and other clinical events&#46;Physical examination including BP&#46;Blood and urinary samples&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3Month 6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Detailed medical history including medication&#44; SAE and other clinical events&#46;Physical examination including BP&#46;Blood and urinary samples&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4Month 12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Detailed medical history including medication&#44; SAE and other clinical events&#46;Physical examination including BP&#46;Blood and urinary samples&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5Month 18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Detailed medical history including medication&#44; SAE and other clinical events&#46;Physical examination including BP&#46;Blood and urinary samples&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6Month 24&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Detailed medical history including medication&#44; SAE and other clinical events&#46;Physical examination including BP&#46;Blood and urinary samples&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7Month 36&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Detailed medical history including medication&#44; SAE and other clinical events&#46;Physical examination including BP&#46;Blood and urinary samples&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2320430.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Schedule of assessments&#46;</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0015"
          "bibliografiaReferencia" => array:25 [
            0 => array:3 [
              "identificador" => "bib0130"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Chronic kidney disease&#58; global dimension and perspectives"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "V&#46; Jha"
                            1 => "G&#46; Garcia-Garcia"
                            2 => "K&#46; Iseki"
                            3 => "S&#46; Naicker"
                            4 => "B&#46; Plattner"
                            5 => "R&#46; Saran"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S0140-6736(13)60687-X"
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet"
                        "fecha" => "2013"
                        "volumen" => "382"
                        "paginaInicial" => "260"
                        "paginaFinal" => "272"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23727169"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0135"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Prevalence of chronic kidney disease in population-based studies&#58; systematic review"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "Q&#46;L&#46; Zhang"
                            1 => "D&#46; Rothenbacher"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/1471-2458-8-117"
                      "Revista" => array:5 [
                        "tituloSerie" => "BMC Public Health"
                        "fecha" => "2008"
                        "volumen" => "8"
                        "paginaInicial" => "117"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18405348"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0140"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Mortality risk stratification in chronic kidney disease&#58; one size for all ages&#63;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46;M&#46; O&#8217;Hare"
                            1 => "D&#46; Bertenthal"
                            2 => "K&#46;E&#46; Covinsky"
                            3 => "C&#46;S&#46; Landefeld"
                            4 => "S&#46; Sen"
                            5 => "K&#46; Mehta"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1681/ASN.2005090986"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Am Soc Nephrol"
                        "fecha" => "2006"
                        "volumen" => "17"
                        "paginaInicial" => "846"
                        "paginaFinal" => "853"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16452492"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0145"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "KDIGO clinical practice guideline for the management of blood pressure in chronic kidney disease&#58; summary of recommendation statements"
                      "autores" => array:1 [
                        0 => array:2 [
                          "colaboracion" => "KDIGO Work Group"
                          "etal" => false
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Kidney Int Suppl"
                        "fecha" => "2012"
                        "volumen" => "2"
                        "paginaInicial" => "341"
                        "paginaFinal" => "342"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0150"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "AIPRD Study Group Progression of chronic kidney disease&#58; the role of blood pressure control&#44; proteinuria&#44; and angiotensin-converting enzyme inhibition&#58; a patient-level meta-analysis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "T&#46;H&#46; Jafar"
                            1 => "P&#46;C&#46; Stark"
                            2 => "C&#46;H&#46; Schmid"
                            3 => "M&#46; Landa"
                            4 => "G&#46; Maschio"
                            5 => "P&#46;E&#46; de Jong"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.7326/0003-4819-139-4-200308190-00006"
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Intern Med"
                        "fecha" => "2003"
                        "volumen" => "139"
                        "paginaInicial" => "244"
                        "paginaFinal" => "252"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12965979"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib0155"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Current guidelines for using angiotensin-converting enzyme inhibitors and angiotensin II-receptor antagonists in chronic kidney disease&#58; is the evidence base relevant to older adults&#63;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "A&#46;M&#46; O&#8217;Hare"
                            1 => "J&#46;S&#46; Kaufman"
                            2 => "K&#46;E&#46; Covinsky"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Ann Intern Med"
                        "fecha" => "2009"
                        "volumen" => "19"
                        "paginaInicial" => "717"
                        "paginaFinal" => "724"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bib0160"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "ESC Scientific Document Group 2018 ESC&#47;ESH Guidelines for the management of arterial hypertension"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "B&#46; Williams"
                            1 => "G&#46; Mancia"
                            2 => "W&#46; Spiering"
                            3 => "E&#46; Agabiti Rosei"
                            4 => "M&#46; Azizi"
                            5 => "M&#46; Burnier"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/eurheartj/ehy339"
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur Heart J"
                        "fecha" => "2018"
                        "volumen" => "39"
                        "paginaInicial" => "3021"
                        "paginaFinal" => "3104"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30165516"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib0165"
              "etiqueta" => "8"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Effect of allopurinol in chronic kidney disease progression and cardiovascular risk"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46; Goicoechea"
                            1 => "S&#46;G&#46; de Vinuesa"
                            2 => "U&#46; Verdalles"
                            3 => "C&#46; Ruiz-Caro"
                            4 => "J&#46; Ampuero"
                            5 => "A&#46; Rinc&#243;n"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.2215/CJN.01580210"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin J Am Soc Nephrol"
                        "fecha" => "2010"
                        "volumen" => "5"
                        "paginaInicial" => "1388"
                        "paginaFinal" => "1393"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20538833"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bib0170"
              "etiqueta" => "9"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "HYVET Stdy Group Treatment of Hypertension in patients 80 years of age or older"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "N&#46; Beckett"
                            1 => "R&#46; Peters"
                            2 => "A&#46; Fletcher"
                            3 => "C&#46;S&#46; Landefeld"
                            4 => "L&#46;V&#46; McFarland"
                            5 => "E&#46;B&#46; Larson"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMoa0801369"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2008"
                        "volumen" => "358"
                        "paginaInicial" => "1887"
                        "paginaFinal" => "1898"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18378519"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib0175"
              "etiqueta" => "10"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "SCOPE Study Group The Study on Cognition and Prognosis in the Elderly &#40;SCOPE&#41;&#58; principal results of a randomized double-blind intervention trial"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "H&#46; Lithel"
                            1 => "L&#46; Hansson"
                            2 => "I&#46; Skoog"
                            3 => "D&#46; Elmfeldt"
                            4 => "A&#46; Hofman"
                            5 => "B&#46; Olofsson"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/00004872-200305000-00011"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Hypertens"
                        "fecha" => "2003"
                        "volumen" => "21"
                        "paginaInicial" => "875"
                        "paginaFinal" => "886"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12714861"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            10 => array:3 [
              "identificador" => "bib0180"
              "etiqueta" => "11"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "ALLHAT findings revisited in the context of subsequent analyses&#44; other trials&#44; and meta-analyses"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46;T&#46; Wright Jr&#46;"
                            1 => "J&#46;L&#46; Probstfield"
                            2 => "W&#46;C&#46; Cushman"
                            3 => "S&#46;L&#46; Pressel"
                            4 => "J&#46;A&#46; Cutler"
                            5 => "B&#46;R&#46; Davis"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1001/archinternmed.2009.60"
                      "Revista" => array:6 [
                        "tituloSerie" => "Arch Intern Med"
                        "fecha" => "2009"
                        "volumen" => "169"
                        "paginaInicial" => "832"
                        "paginaFinal" => "842"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19433694"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            11 => array:3 [
              "identificador" => "bib0185"
              "etiqueta" => "12"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Renal outcomes in high-risk hypertensive patients treated with an angiotensin-converting enzyme inhibitor or a calcium channel blocker vs&#46; a diuretic&#58; a report from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial &#40;ALLHAT&#41;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46; Rahman"
                            1 => "S&#46; Pressel"
                            2 => "B&#46;R&#46; Davis"
                            3 => "C&#46; Nwachuku"
                            4 => "J&#46;T&#46; Wright Jr&#46;"
                            5 => "P&#46;K&#46; Whelton"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1001/archinte.165.8.936"
                      "Revista" => array:6 [
                        "tituloSerie" => "Arch Intern Med"
                        "fecha" => "2005"
                        "volumen" => "165"
                        "paginaInicial" => "936"
                        "paginaFinal" => "946"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15851647"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            12 => array:3 [
              "identificador" => "bib0190"
              "etiqueta" => "13"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Effect of telmisartan on renal outcomes&#58; a randomized trial"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46;F&#46; Mann"
                            1 => "R&#46;E&#46; Schmieder"
                            2 => "L&#46; Dyal"
                            3 => "M&#46;J&#46; McQueen"
                            4 => "H&#46; Schumacher"
                            5 => "J&#46; Pogue"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.7326/0003-4819-151-1-200907070-00122"
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Intern Med"
                        "fecha" => "2009"
                        "volumen" => "151"
                        "paginaInicial" => "1"
                        "paginaFinal" => "10"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19451556"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            13 => array:3 [
              "identificador" => "bib0195"
              "etiqueta" => "14"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Heart outcomes prevention evaluation study investigators"
                      "autores" => array:1 [
                        0 => array:2 [
                          "colaboracion" => "Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus&#58; results of the HOPE study and MICRO-HOPE substudy"
                          "etal" => false
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet"
                        "fecha" => "2000"
                        "volumen" => "355"
                        "paginaInicial" => "253"
                        "paginaFinal" => "259"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10675071"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            14 => array:3 [
              "identificador" => "bib0200"
              "etiqueta" => "15"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "B&#46;M&#46; Brenner"
                            1 => "M&#46;E&#46; Cooper"
                            2 => "D&#46; de Zeeuw"
                            3 => "W&#46;F&#46; Keane"
                            4 => "W&#46;E&#46; Mitch"
                            5 => "H&#46;H&#46; Parving"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMoa011161"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2001"
                        "volumen" => "345"
                        "paginaInicial" => "861"
                        "paginaFinal" => "869"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11565518"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            15 => array:3 [
              "identificador" => "bib0205"
              "etiqueta" => "16"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "E&#46;J&#46; Lewis"
                            1 => "L&#46;G&#46; Hunsicker"
                            2 => "W&#46;R&#46; Clarke"
                            3 => "T&#46; Berl"
                            4 => "M&#46;A&#46; Pohl"
                            5 => "J&#46;B&#46; Lewis"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2001"
                        "volumen" => "345"
                        "paginaInicial" => "851"
                        "paginaFinal" => "860"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            16 => array:3 [
              "identificador" => "bib0210"
              "etiqueta" => "17"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Effect of blood pressure lowering and antihypertensive drug class on progression of hypertensive kidney disease&#58; results from the AASK trial"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46;T&#46; Wright Jr&#46;"
                            1 => "G&#46; Bakris"
                            2 => "T&#46; Greene"
                            3 => "L&#46;Y&#46; Agodoa"
                            4 => "L&#46;J&#46; Appel"
                            5 => "J&#46; Charleston"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "J Am Med Assoc"
                        "fecha" => "2002"
                        "volumen" => "288"
                        "paginaInicial" => "2421"
                        "paginaFinal" => "2431"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            17 => array:3 [
              "identificador" => "bib0215"
              "etiqueta" => "18"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The impact of stopping inhibitors of the renin&#8211;angiotensin system in patients with advanced chronic kidney disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "A&#46; Ahmed"
                            1 => "N&#46; Kamath"
                            2 => "M&#46; El Kossi"
                            3 => "A&#46; El Nahas"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/ndt/gfp511"
                      "Revista" => array:6 [
                        "tituloSerie" => "Nephrol Dial Transplant"
                        "fecha" => "2010"
                        "volumen" => "25"
                        "paginaInicial" => "3977"
                        "paginaFinal" => "3982"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19820248"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            18 => array:3 [
              "identificador" => "bib0220"
              "etiqueta" => "19"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Renal outcomes with telmisartan&#44; ramipril&#44; or both&#44; in people at high vascular risk &#40;the ONTARGET study&#41;&#58; a multicentre&#44; randomised&#44; double-blind&#44; controlled trial"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46;F&#46; Mann"
                            1 => "R&#46;E&#46; Schmieder"
                            2 => "M&#46; McQueen"
                            3 => "L&#46; Dyal"
                            4 => "H&#46; Schumacher"
                            5 => "J&#46; Pogue"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S0140-6736(08)61236-2"
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet"
                        "fecha" => "2008"
                        "volumen" => "372"
                        "paginaInicial" => "547"
                        "paginaFinal" => "553"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18707986"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            19 => array:3 [
              "identificador" => "bib0225"
              "etiqueta" => "20"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Multicentre randomized controlled trial of angiotensin-converting enzyme inhibitor&#47;angiotensin receptor blocker withdrawal in advanced renaldisease&#58; the STOP-ACEi trial"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "S&#46; Bhandari"
                            1 => "N&#46; Ives"
                            2 => "E&#46;A&#46; Brettell"
                            3 => "M&#46; Valente"
                            4 => "P&#46; Cockwell"
                            5 => "P&#46;S&#46; Topham"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/ndt/gfv346"
                      "Revista" => array:6 [
                        "tituloSerie" => "Nephrol Dial Transplant"
                        "fecha" => "2016"
                        "volumen" => "31"
                        "paginaInicial" => "255"
                        "paginaFinal" => "261"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26429974"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            20 => array:3 [
              "identificador" => "bib0230"
              "etiqueta" => "21"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Effects of an angiotensin-converting-enzyme inhibitor&#44; ramipril&#44; on cardiovascular events in high-risk patients"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "S&#46; Yusuf"
                            1 => "P&#46; Sleight"
                            2 => "J&#46; Pogue"
                            3 => "J&#46; Bosch"
                            4 => "R&#46; Davies"
                            5 => "G&#46; Dagenais"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJM200001203420301"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2000"
                        "volumen" => "342"
                        "paginaInicial" => "145"
                        "paginaFinal" => "153"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10639539"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            21 => array:3 [
              "identificador" => "bib0235"
              "etiqueta" => "22"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Efficacy of perindopril in reduction of cardiovascular events among patients with stable coronary artery disease&#58; randomised&#44; double-blind&#44; placebo-controlled&#44; multicentre trial &#40;the EUROPA study&#41;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "K&#46;M&#46; Fox"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/s0140-6736(03)14286-9"
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet"
                        "fecha" => "2003"
                        "volumen" => "362"
                        "paginaInicial" => "782"
                        "paginaFinal" => "788"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/13678872"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            22 => array:3 [
              "identificador" => "bib0240"
              "etiqueta" => "23"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "2017 ACC&#47;AHA&#47;HFSA Focused Update of the 2013 ACCF&#47;AHA Guideline for the Management of Heart Failure&#58; A Report of the American College of Cardiology&#47;American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "C&#46;W&#46; Yancy"
                            1 => "M&#46; Jessup"
                            2 => "B&#46; Bozkurt"
                            3 => "J&#46; Butler"
                            4 => "D&#46;E&#46; Casey Jr&#46;"
                            5 => "M&#46;M&#46; Colvin"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1161/CIR.0000000000000509"
                      "Revista" => array:6 [
                        "tituloSerie" => "Circulation"
                        "fecha" => "2017"
                        "volumen" => "136"
                        "paginaInicial" => "e137"
                        "paginaFinal" => "e161"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28455343"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            23 => array:3 [
              "identificador" => "bib0245"
              "etiqueta" => "24"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Elevated relative mortality risk with mild-to-moderate chronic kidney disease decreases with age"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "N&#46;T&#46; Raymond"
                            1 => "D&#46; Zehnder"
                            2 => "S&#46;C&#46; Smith"
                            3 => "J&#46;A&#46; Stinson"
                            4 => "H&#46; Lehnert"
                            5 => "R&#46;M&#46; Higgins"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/ndt/gfm396"
                      "Revista" => array:6 [
                        "tituloSerie" => "Nephrol Dial Transplant"
                        "fecha" => "2007"
                        "volumen" => "22"
                        "paginaInicial" => "3214"
                        "paginaFinal" => "3220"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17631511"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            24 => array:3 [
              "identificador" => "bib0250"
              "etiqueta" => "25"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Use of renin&#8211;angiotensin system blockade in advanced CKD&#58; an NKF-KDOQI controversies report"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46;R&#46; Weir"
                            1 => "J&#46;I&#46; Lakkis"
                            2 => "B&#46; Jaar"
                            3 => "M&#46;V&#46; Rocco"
                            4 => "M&#46;J&#46; Choi"
                            5 => "H&#46;J&#46; Kramer"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1053/j.ajkd.2018.06.010"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Kidney Dis"
                        "fecha" => "2018"
                        "volumen" => "72"
                        "paginaInicial" => "873"
                        "paginaFinal" => "884"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30201547"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
          ]
        ]
      ]
    ]
  ]
  "idiomaDefecto" => "en"
  "url" => "/18891837/0000003700000003/v1_202006200856/S1889183720300271/v1_202006200856/en/main.assets"
  "Apartado" => array:4 [
    "identificador" => "9105"
    "tipo" => "SECCION"
    "es" => array:2 [
      "titulo" => "Originales"
      "idiomaDefecto" => true
    ]
    "idiomaDefecto" => "es"
  ]
  "PDF" => "https://static.elsevier.es/multimedia/18891837/0000003700000003/v1_202006200856/S1889183720300271/v1_202006200856/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/"
  "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1889183720300271?idApp=UINPBA00004N"
]

Información del artículo

ISSN: 18891837
Idioma original: Inglés

DOI:10.1016/j.hipert.2020.02.005

Datos actualizados diariamente

año/Mes	Html	Pdf	Total

2024 Octubre	0	4	4
2024 Septiembre	0	8	8
2024 Agosto	0	4	4
2024 Julio	0	2	2
2024 Junio	0	6	6
2024 Mayo	0	1	1
2024 Abril	0	7	7
2024 Marzo	0	4	4
2024 Febrero	1	2	3
2024 Enero	1	3	4
2023 Noviembre	0	2	2
2023 Octubre	0	6	6
2023 Septiembre	0	14	14
2023 Agosto	0	2	2
2023 Julio	0	9	9
2023 Junio	0	1	1
2023 Abril	0	1	1
2023 Marzo	1	2	3
2023 Febrero	0	1	1
2022 Diciembre	0	1	1
2022 Noviembre	0	7	7
2021 Diciembre	1	0	1
2021 Octubre	1	0	1
2021 Abril	0	8	8
2021 Febrero	1	0	1
2020 Diciembre	2	4	6
2020 Octubre	2	0	2
2020 Septiembre	1	0	1
2020 Agosto	1	0	1
2020 Julio	3	0	3
2020 Junio	1	0	1
2020 Mayo	0	2	2

Mostrar todo

Indexada en:

Síguenos:

Suscribirse:

Estadísticas

Indexada en:

Síguenos:

Suscribirse:

Estadísticas

Suscríbase a la newsletter