Kidney and hypertension in older adults | Medicina Clínica (English Edition)

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"documento" => "article" "crossmark" => 1 "subdocumento" => "sco" "cita" => "Med Clin. 2021;157:176-7" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:10 [ "idiomaDefecto" => true "cabecera" => "Editorial article" "titulo" => "A long and stony road to the correct treatment of obesity" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "176" "paginaFinal" => "177" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Un largo y pedregoso camino hacia el correcto tratamiento de la obesidad" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Albert Lecube, Andreea Ciudin" "autores" => array:2 [ 0 => array:2 [ "nombre" => "Albert" "apellidos" => "Lecube" ] 1 => array:2 [ "nombre" => "Andreea" "apellidos" => "Ciudin" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0025775321003262" "doi" => "10.1016/j.medcli.2021.06.004" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0025775321003262?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S238702062100379X?idApp=UINPBA00004N" "url" => "/23870206/0000015700000004/v2_202201010719/S238702062100379X/v2_202201010719/en/main.assets" ] "en" => array:20 [ "idiomaDefecto" => true "cabecera" => "Review" "titulo" => "Kidney and hypertension in older adults" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "178" "paginaFinal" => "184" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Hanane Bouarich, Alina Chávez Guillén, Diego Rodríguez Puyol" "autores" => array:3 [ 0 => array:3 [ "nombre" => "Hanane" "apellidos" => "Bouarich" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 1 => array:3 [ "nombre" => "Alina" "apellidos" => "Chávez Guillén" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 2 => array:4 [ "nombre" => "Diego" "apellidos" => "Rodríguez Puyol" "email" => array:1 [ 0 => "drodriguez.hupa@gmail.com" ] "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Sección de Nefrología, Hospital Universitario Príncipe de Asturias, Alcalá de Henares, Madrid, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Departamento de Medicina y Especialidades Médicas, Universidad de Alcalá, IRYCIS, Alcalá de Henares, 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" => "Riñón e hipertensión en el anciano" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1210 "Ancho" => 2333 "Tamanyo" => 236064 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Mechanisms of kidney ageing. An integrated view." ] ] ] "textoCompleto" => "DemographicsAgeing is associated with different degrees of chronic kidney disease (CKD), although 11% of older patients diagnosed with CKD do not have any underlying nephropathy, suggesting that ageing itself may condition a progressive deterioration of kidney function<a class="elsevierStyleCrossRef" href="#bib0005">1</a>. The prevalence of CKD in Spain in those over the age of 65 is above 20%, and approximately 38% of adults over 70 have an estimated glomerular filtration rate (GFR) of less than 60 ml/min/1.73 m2<a class="elsevierStyleCrossRef" href="#bib0010">2</a>. It is estimated that almost half of people over the age of 75 meet the criteria set by the Kidney Disease Improving Global Outcome (KDIGO) guidelines for a diagnosis of CKD<a class="elsevierStyleCrossRef" href="#bib0015">3</a>. The incidence of dialysis initiation has also been shown to increase with age. According to the US Data System, the median age of patients starting dialysis is 65 years, but the fastest growing group is found in those over 75<a class="elsevierStyleCrossRef" href="#bib0020">4</a>. The Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines establish a classification of CKD based on the degree of GFR and/or presence of kidney damage signs and consider the different stages of CKD to be valid for people of all ages<a class="elsevierStyleCrossRef" href="#bib0025">5</a>. However, there is much debate as to what is the normal range of renal function in the elderly, and whether decreased GFR is due to a physiological ageing process or whether it is due to intrinsic renal disease.Anatomical and functional changes of the ageing processRenal structural changesThe main renal structural changes associated with ageing are quite nonspecific and not always easy to distinguish from the changes produced by other processes, such as arterial hypertension (HTN) or diabetes (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). Perhaps the most characteristic features are the progressive decrease in renal volume, estimated to be around 10% per decade from the fourth decade of life onwards, the decrease in the number of intact glomeruli, which in turn appear hypertrophic, glomerular sclerosis and interstitial fibrosis<a class="elsevierStyleCrossRefs" href="#bib0030">6,7</a>. The earliest descriptions of nephron mass reduction with ageing are quite old and come from autopsy studies. Recently, Denic et al.<a class="elsevierStyleCrossRef" href="#bib0035">7</a> showed that the number of intact glomeruli decreases from approximately one million in the second decade of life to 600,000 in the eighth decade, with an increase in histologically detectable sclerosed glomeruli of up to 10% and a statistically significant negative relationship between the number of glomeruli and their volume<a class="elsevierStyleCrossRef" href="#bib0040">8</a>.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>Renal functional changesThe GFR decreases with age, but several studies question whether there is an unambiguous relationship between age and the decrease in GFR. The Baltimore Longitudinal Study on Ageing, in a group of 254 people with a 24 year follow-up, without HTN or other causes of CKD showed that the mean decrease in GFR was 0.75 ml/min/year, a third of the individuals had their GFR completely stable, and even a small group showed a small increase in GFR<a class="elsevierStyleCrossRef" href="#bib0045">9</a>. Other longitudinal studies have confirmed similar results, estimating that the reduction in GFR with age can range from 0.4 ml/min to 3.8 ml/min per year<a class="elsevierStyleCrossRefs" href="#bib0050">10,11</a>. This variability lies in the different rate of nephron loss in different individuals, but also in the adaptive capacity of intact glomeruli. In fact, the glomeruli of aged kidneys behave like hyperfiltrating glomeruli, with a dissociation between anatomical changes and loss of function (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>)<a class="elsevierStyleCrossRef" href="#bib0040">8</a>.<elsevierMultimedia ident="tbl0010"></elsevierMultimedia>Ageing is characterised by progressive tubular dysfunction. Basically, the elderly patient usually maintains a sodium balance similar to that of young patients; however, in situations of volume depletion the response to the reduction in sodium excretion is significantly slower. This phenomenon contributes to the susceptibility of the elderly to the development of acute renal failure (ARF). Potassium excretion is decreased by a reduction in the transtubular potassium gradient, the presence of a certain degree of hyporeninaemic hypoaldosteronism and a decrease in the sodium load reaching the distal nephron in situations of volume depletion. This somewhat explains the predisposition to drug-induced hyperkalaemia in elderly patients<a class="elsevierStyleCrossRef" href="#bib0060">12</a>. The urine concentration and dilution mechanism is also altered, explaining the high incidence of nocturia, the predisposition to dehydration and hypernatremia in cases of low intake, and hyponatremia when excess fluids are administered<a class="elsevierStyleCrossRefs" href="#bib0065">13,14</a>.With age, renal renin production decreases, contributing to a reduction in plasma renin activity and, therefore, angiotensin II and aldosterone synthesis, with their respective impact on electrolyte homeostasis and blood volume<a class="elsevierStyleCrossRef" href="#bib0070">14</a>. The generation of natriuretic substances such as PGE2 and dopamine is reduced, increasing sensitivity to salt<a class="elsevierStyleCrossRef" href="#bib0075">15</a>. Plasma levels of 1,25-dihydroxyvitamin D are generally in the low-normal range, indicating a decrease in renal hydroxylation of vitamin D<a class="elsevierStyleCrossRef" href="#bib0080">16</a>. Serum erythropoietin increases with age, due to a complex mechanism that is not entirely well defined<a class="elsevierStyleCrossRef" href="#bib0085">17</a>. Finally, renal formation of klotho, a cofactor of FGF23 to which systemic actions are attributed, decreases with age, which may contribute to ageing in other parts of the body<a class="elsevierStyleCrossRef" href="#bib0090">18</a>.Mechanisms involved in kidney ageingTranscriptome analysis of aged kidneys has identified overexpression of genes related to extracellular matrix synthesis and inflammation<a class="elsevierStyleCrossRef" href="#bib0095">19</a>. These two factors play a key role in the development of renal structural and functional alterations with ageing, but they are only the final common pathway of a process that is actively being studied (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). The molecular basis of the renal ageing phenomenon includes cellular senescence, which includes genomic instability, loss of telomeres and DNA repeats at the end of chromosomes as a result of loss of telomerase activity, chronic oxidative damage contributing to telomeric shortening resulting in the senescent phenotype, a certain genetic programming favouring accelerated cellular ageing, with subsequent inflammatory phenotype, thus inducing changes in the kidney<a class="elsevierStyleCrossRefs" href="#bib0100">20,21</a> and finally cell death. This cell damage is essentially determined by chronic inflammation and cellular senescence. The accumulation of non-dividing senescent cells can compromise the tissue's capacity for renewal and repair. In addition, certain genes that are overexpressed by the senescent response may encode for soluble proteins (cytokines, adhesion molecules and growth factors) that can alter the tissue microenvironment, thereby altering its structure and function<a class="elsevierStyleCrossRefs" href="#bib0110">22–24</a>. Along with this, environmental and hormonal factors can also influence genetic determinants, affecting renal behaviour in old age (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).<elsevierMultimedia ident="fig0005"></elsevierMultimedia>Clinical implicationsGlomerular filtration rate measurement in clinical practiceIn clinical practice, the quantification of renal function often uses formulae developed to estimate GFR from serum creatinine and physical and laboratory parameters, all of which have a certain degree of inaccuracy and are not validated in individuals over 70 years of age. The most accurate and the one most used today is the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), created in 2009<a class="elsevierStyleCrossRef" href="#bib0125">25</a>.Clinical guidelines define CKD as the presence for at least 3 months of a GFR of less than 60 ml/min/1.73 m2 or evidence of structural or functional renal abnormalities other than GFR<a class="elsevierStyleCrossRefs" href="#bib0015">3,5</a>. It is these abnormalities that should be evaluated in the elderly and, in their absence, moderate reductions in GFR should not be considered pathological, although they should be considered when administering drugs. In summary, we could conclude that individuals over the age of 75 with a GFR above 45 ml/min/1.73 m2 and without other renal abnormalities should not be considered nephrological patients.Clinical problems associated with kidney dysfunctionThe reduction in renal haemodynamic and functional reserve that occurs with ageing may compromise the organ's adaptation to acute ischaemia or following exposure to nephrotoxic drugs, increasing susceptibility to ARF. The existence of previous CKD has been described as the greatest risk factor for developing ARF. Thus, the risk doubles for GFR between 45-59 ml/min compared to GFR > 60 ml/min<a class="elsevierStyleCrossRef" href="#bib0130">26</a>. Proteinuria also seems to double the risk of ARF regardless of GFR<a class="elsevierStyleCrossRef" href="#bib0135">27</a>. Other factors, such as the higher prevalence of certain comorbidities in the elderly, polypharmacy, and the fact that certain procedures (contrasts, surgical interventions) are performed more often in this population group, may also contribute to increasing the incidence of ARF<a class="elsevierStyleCrossRef" href="#bib0140">28</a>. It should be underlined that age over 65 is a risk factor for progression to CKD after an episode of ARF. A meta-analysis reveals that 31% of patients >65 did not recover their previous kidney function after an episode of ARF compared to 26% in younger patients<a class="elsevierStyleCrossRef" href="#bib0145">29</a>.As in younger people, the presence of CKD in the elderly can be associated with a number of complications. In general, the clinical manifestations of CKD develop progressively, with great variability from patient to patient, depending on the rate of progression and the amount of functioning renal mass. A GFR of less than 30 ml/min usually signals the borderline at which CKD becomes symptomatic, after which a wide range of clinical manifestations develop in parallel with the progressive stage, including water and sodium metabolism disorders, which can lead to heart failure (HF), HTN, oedema and hyponatraemia; electrolyte disturbances, with hyperkalaemia being the most relevant, bone-mineral metabolism disturbances with the occurrence of hypocalcaemia and hyperphosphatemia, responsible for the pruritus typical of CKD. Metabolic acidosis, normocytic normochromic anaemia, altered lipid profile with elevated triglycerides and LDL cholesterol may also occur together with low HDL cholesterol levels, glucose intolerance, hyperuricemia, and increased bleeding time due to platelet dysfunction, thus increasing the risk of bleeding in these patients<a class="elsevierStyleCrossRefs" href="#bib0015">3,5</a>. Intervention on these complications of CKD should be individualised according to functional status, accompanying symptoms and disease progression. The ideal treatment should be aimed at improving the patient's quality of life rather than addressing isolated laboratory figures. Adequate control of cardiovascular risk factors, anaemia, acidosis, and malnutrition are key to achieving this effect. It should be noted that, in the elderly patient, the clinical symptoms of CKD are often absent and that in many cases the casual finding of elevated urea and creatinine levels points to the diagnosis.The factors for progression of CKD in the elderly patient are the classic ones described for the general population plus hyperfiltration. It is therefore recommended to correct modifiable risk factors and to intervene on the glomerular overload caused by the reduction in renal mass. In this sense, adequate control of blood pressure levels, also modifying intrarenal hemodynamics by blocking angiotensin, is essential to prevent the potential reduction in GFR. Proteinuria is a clinical marker that must be considered.Medication dose adjustment to glomerular filtration rateOne of the greatest consequences of ageing is the increased susceptibility to drug toxicity. Decreasing renal excretory capacity and, to a lesser extent, changes in hepatic metabolism and changes in body composition that occur with age, contribute to changes in the pharmacokinetics of many drugs<a class="elsevierStyleCrossRef" href="#bib0150">30</a>. The same is true for the pharmacodynamics of many drugs: age regulates the sensitivity and physiological response to their actions. When polypharmacy and polypathology are added to this, the medication dose adjustment becomes a complex problem. It is recommended to adjust the dose to the estimated renal function, whether it is a patient with a diagnosis of CKD or a decrease in GFR associated with ageing.Renal hypertension in the elderlyDemographicsHTN is one of the most prevalent diseases in the world today. Its global prevalence in developed countries is around 25%, while in the elderly it can be 60–80%. With an estimated 4.4% of the world's population being over 80  years of age by 2050, the global prevalence of HTN will increase steadily over the next few years<a class="elsevierStyleCrossRef" href="#bib0155">31</a>.During the ageing process, various structural and functional changes and modifications occur in the cardiovascular system that favour an increase in systolic blood pressure (SBP). This increase is evidenced in 65% of patients over the age of 60 and in 90% of those over 70, with a higher incidence in women. Systolic HTN is associated with a significant increase in cardiovascular risk<a class="elsevierStyleCrossRef" href="#bib0160">32</a>. Diastolic blood pressure (DBP), however, undergoes a reverse process, starting to decline from the age of 50 in both sexes, with a consequent increase in pulse pressure (PP). PP is defined as the difference between SBP and DBP and is a powerful predictor for the development of cardiovascular events<a class="elsevierStyleCrossRef" href="#bib0165">33</a>.Anatomical and functional changes of the ageing processArterial wall modificationsThe changes associated with ageing that favour an increase in blood pressure (BP) generally have to do with the changes our body undergoes with age. Environmental factors linked to the lifestyle habits of each individual, such as salt intake, smoking and overweight, as well as genetic factors, also play a role. The most characteristic and significant structural change that occurs with ageing is a loss of elasticity and distensibility of the great arteries, with an increase in their stiffness and a decrease in their capacitance, which determines an impairment to buffer the pressure generated from the left ventricle, thus leading to a progressive increase in SBP. When these same changes take place in the arteries of medium and small calibre, what occurs is an increase in peripheral resistance, increasing DBP<a class="elsevierStyleCrossRef" href="#bib0170">34</a>.Structural changes in the arterial wall are involved in the etiopathogenesis of these processes, especially in its intima and media layers. The arterial media layer is made up of smooth muscle cells surrounded by extracellular matrix, which in turn is made up of collagen and elastin. With age, the endothelium becomes more permeable to the passage of macromolecules and the deposits of calcium, phospholipids and cholesterol esters increase. The elastic fibres of the internal elastic lamina lose their elasticity and their degradation is accelerated by an increase in the activity of elastases. There is an expansion of the extracellular matrix by deposition of collagen, elastin and proteoglycans and hypertrophy and hyperplasia of smooth muscle cells<a class="elsevierStyleCrossRef" href="#bib0175">35</a>.Endothelial dysfunctionArterial stiffness is not only a consequence of structural changes in the vascular wall, but also depends on changes in the synthesis of vasoactive endothelial mediators. During ageing, endothelium-dependent vascular functions are altered, a phenomenon called endothelial dysfunction, which is characterised by an imbalance between the synthesis and release of vasodilator and vasoconstrictor substances, especially affecting the nitric oxide (NO)-dependent vasodilator response and favouring vasoconstriction and increased peripheral vascular resistances<a class="elsevierStyleCrossRefs" href="#bib0180">36,37</a>. In turn, NO deficiency negatively influences leukocyte adhesion, platelet aggregation and smooth muscle cell proliferation, thus contributing to the development of atherosclerosis. In addition, the endothelial secretion of certain substances, such as interleukins, endothelin, or insulin growth factor 1, would also favour the formation of collagen matrix in the arterial wall<a class="elsevierStyleCrossRef" href="#bib0190">38</a>. Data from experimental and clinical studies link elevated levels of asymmetric dimethylarginine (ADMA), together with reduced NO bioavailability, to the endothelial dysfunction observed in HTN in the elderly<a class="elsevierStyleCrossRef" href="#bib0195">39</a>.Changes in neurohormonal regulatory mechanismsAn increase in angiotensin II, angiotensin converting enzyme and mineralocorticoid receptor levels is observed in ageing. Elevated levels of these factors stimulate extracellular matrix production and result in the development of inflammation, oxidative stress, and fibrosis, thus contributing to the arterial stiffness seen with age. Evidence from recent years points to the renin/prorenin receptor and its profibrosing role as another angiotensin II independent pathway to increase extracellular matrix<a class="elsevierStyleCrossRef" href="#bib0200">40</a>.The role of the sympathetic nervous system in the maintenance of hypertension in humans is well known. Circulating catecholamine levels increase with age, more in women than in men, generally after the age of 40. However, beta-adrenergic vasodilation of vascular smooth muscle decreases with ageing due to a decrease in both the number and affinity of beta receptors.In the autonomic nervous system, age-related reduction in baroreceptor function contributes to the high prevalence of orthostatic hypotension. It has also been shown that arterial stiffness alters the homeostatic mechanism responsible for maintaining the stability of BP and tissue perfusion during different physiological conditions, such as orthostatism, exercise, postpartum or stress, thus conditioning a great variability of SBP in these situations <a class="elsevierStyleCrossRef" href="#bib0205">41</a>.Clinical implicationsCardiovascular complicationsIn the elderly, isolated systolic HTN is the most prevalent form of HTN. There are numerous studies that relate it to an increase in cardiovascular morbidity and mortality. The Framingham study, with a follow-up of more than 30 years, found that patients with isolated systolic HTN had an increased risk of death from cardiovascular disease of 1.8 in males and 4.7 in females<a class="elsevierStyleCrossRef" href="#bib0210">42</a>. Another epidemiological study, the Multiple Risk Factor Intervention Trial (MRFIT), with a follow-up of more than 300,000 individuals over 10 years, also evidenced a significant increase in cardiovascular mortality linked to SBP values<a class="elsevierStyleCrossRef" href="#bib0215">43</a>. Other studies, on the other hand, suggest that BP has a limited predictive value for total mortality after the age of 70.The prevalence of coronary heart disease is higher in hypertensive than in normotensive elderly, although this difference becomes less pronounced with every decade of increase. Left ventricular hypertrophy (LVH) and cardiac diastolic dysfunction are quite common in these patients, and it is possible that this difficulty in cardiac filling is primarily responsible for the low cardiac output and the development of HF<a class="elsevierStyleCrossRef" href="#bib0220">44</a>. Atrial fibrillation clearly increases its incidence in hypertensive elderly patients and has been associated with an increased risk of cardiovascular events, stroke, and impaired kidney function. HTN, age, and proteinuria have a negative impact on the course of CKD, which in turn is associated with increased cardiovascular risk. SBP is an independent marker of worsening kidney function in the elderly with isolated systolic HTN. Regarding the risk of cerebrovascular disease (CVD), the association of HTN and ischemic or hemorrhagic CVD increases with age, with isolated systolic HTN being an important risk factor.Impact on neurocognitive functionsNumerous observational studies have documented the association between elevated BP levels in middle-aged people and the risk of vascular dementia and Alzheimer's disease. This relationship was first observed in the Framingham study, in which elevated BP levels detected in the previous 20 years had an inverse correlation with cognitive status in untreated hypertensive patients<a class="elsevierStyleCrossRef" href="#bib0210">42</a>. Since this initial observation, there have been numerous epidemiological studies that have verified this association between hypertension and cognitive impairment<a class="elsevierStyleCrossRef" href="#bib0225">45</a>. Others, however, have not demonstrated this association, observing discrepancies between the results of various studies. The same occurs with the results of the studies that analysed the decrease in the incidence of dementia with antihypertensive treatment. While the Syst-Eur and PROGRESS studies showed a decrease in the incidence of dementia in the treatment group<a class="elsevierStyleCrossRefs" href="#bib0230">46,47</a>, in the SCOPE, SHEP and HYVET studies these differences were not significant<a class="elsevierStyleCrossRefs" href="#bib0240">48–50</a>.TreatmentTherapeutic targetsUntil relatively recently, it was not clear whether or not to treat hypertension in the elderly. Currently, there is sufficient evidence on the benefit of hypertension management in the elderly population, at least in terms of cardiovascular morbidity and mortality since there does not seem to be a clear impact on cognitive functions. A Cochrane review of 12 clinical trials showed that adequate management of hypertension in people over 60 years of age was associated with a reduction in mortality. Another review of 5 clinical trials by MacMahon and Rodgers<a class="elsevierStyleCrossRef" href="#bib0255">51</a> on antihypertensive treatment and reduction of cardiovascular morbidity and mortality in the elderly demonstrated a reduction in stroke incidence of 34%, in coronary events of 19% and in overall cardiovascular mortality of 23%. These results were observed with a reduction of 12−14 mmHg in SBP and 5−6 mmHg in DBP, with a follow-up period of 5 years. Other intervention studies carried out in the elderly population have also shown the benefit of treating both HTN and isolated systolic HTN<a class="elsevierStyleCrossRefs" href="#bib0230">46–49</a>. Thus, octogenarians in the HYVET study showed a 30% reduction in the rate of stroke, a 64% decrease in HF episodes and a 21% decrease in the occurrence of major cardiovascular events and all-cause mortality<a class="elsevierStyleCrossRef" href="#bib0250">50</a>.It is difficult to find consensus on BP target in the different guidelines for the management of HTN in the elderly. <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> tries to summarize the opinions of the different scientific societies<a class="elsevierStyleCrossRefs" href="#bib0260">52–56</a>. In general, there is a tendency to recommend increasingly intensive BP monitoring. However, the therapeutic target must be individualized according to the clinical characteristics of each patient and the individual tolerance to the decrease in BP levels.<elsevierMultimedia ident="tbl0015"></elsevierMultimedia>Therapeutic strategiesAs in any patient with essential HTN, lifestyle modifications are the first step to consider in the treatment of hypertensive older people. The measures are the same as those suggested in other populations, and the TONE study has confirmed their usefulness<a class="elsevierStyleCrossRef" href="#bib0285">57</a>. Perhaps special attention should be paid to weight loss, as potential loss of muscle mass is not advisable in older people.Drug therapy must be started after failure of lifestyle modification measures and must be individualized, choosing the drug that best controls BP and with the fewest side effects. It is important to bear in mind a number of clinical aspects specific to this group of patients, such as age-related physiological changes, the presence of comorbidities, common polypharmacy, and cognitive function. In this sense, the studies that have analysed aspects of quality of life have ruled out any negative impact with antihypertensive treatment in this population, although some drugs may have a negative impact, such as beta-blockers, which in the TONE study were associated with major depressive symptoms.In view of the experience accumulated in the various published clinical trials, most international guidelines propose the same antihypertensive drugs that are used in young patients and that include the main therapeutic groups: thiazide diuretics, calcium channel blockers, angiotensin converting enzyme inhibitors (ACEI), angiotensin II receptor blockers (ARBs) and beta-blockers. The American guidelines do not specifically recommend any drug in the antihypertensive treatment of patients over 60<a class="elsevierStyleCrossRef" href="#bib0270">54</a>. The British National Institute for Health Care Excellence (NICE) guidelines do not include beta-blockers as the first line of treatment in older patients<a class="elsevierStyleCrossRef" href="#bib0290">58</a>. European guidelines favour the use of calcium channel blockers or thiazide diuretics in the absence of comorbidities that determine the use of other antihypertensives<a class="elsevierStyleCrossRef" href="#bib0280">56</a>. Recently, based on the results of different studies, it has been proposed that patients over 80 years of age should be prescribed ACEI or ARBs among the first-line drugs<a class="elsevierStyleCrossRefs" href="#bib0260">52–57</a>. The use of alpha blockers as first-line therapeutic agents is not generally recommended.A significant percentage of older patients develop mainly systolic hypertension, with a significant increase in PP, responding inadequately to the above therapies and presenting extemporaneous elevations of their SBP, often related to emotional or physical stress, leading to recurrent emergency interventions. It should be remembered the stiffness of the large central thoracic arteries is critical in the genesis of the condition in these patients, and that the elasticity of these arteries cannot be restored. In these patients, consideration should be given to the appropriate use of drugs to reduce cardiac output, which, together with the capacitance of the great arteries, is responsible for SBP. Drugs such as diuretics or beta-blockers may be useful in treating these patients but should be used with caution because of possible side effects.It is worth noting that a new approach to the management of HTN is becoming increasingly relevant, with a focus on making nocturnal blood pressure a validated therapeutic target. Different studies have confirmed that nocturnal blood pressure is the best indicator of cardiovascular and cerebrovascular risk and that reducing it increases survival (MAPEC, The Hygia Chronotherapy Trial, HOPE, The Syst.Eur trial)<a class="elsevierStyleCrossRef" href="#bib0295">59</a>. The study by Hermida et al.<a class="elsevierStyleCrossRef" href="#bib0300">60</a> provides robust evidence on the safety and efficacy of the nocturnal strategy of antihypertensive treatment and reinforces the importance of adequate blood pressure control on long-term prognosis, with promising results on cardiovascular benefits that translate into a reduction of cardiovascular and cerebrovascular risk by 50–60%, with this benefit being maintained in renal patients. The study also endorses ambulatory blood pressure monitoring (ABPM) as the best tool for the diagnosis of hypertension and for predicting the risk of heart attack and stroke and justifies its routine use in the clinic.FundingThe project has been financed with funds from the Carlos III Health Institute (PI17/01513, RD16/0009/0018) and of the Community of Madrid (NOVELREN-CM/CLINIREN).Conflict of interestsThe authors declare no conflict of interest." "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:3 [ "identificador" => "xres1639440" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1461898" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1639441" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1461899" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Demographics" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Anatomical and functional changes of the ageing process" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Renal structural changes" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Renal functional changes" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Mechanisms involved in kidney ageing" ] ] ] 6 => array:3 [ "identificador" => "sec0030" "titulo" => "Clinical implications" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0035" "titulo" => "Glomerular filtration rate measurement in clinical practice" ] 1 => array:2 [ "identificador" => "sec0040" "titulo" => "Clinical problems associated with kidney dysfunction" ] 2 => array:2 [ "identificador" => "sec0045" "titulo" => "Medication dose adjustment to glomerular filtration rate" ] ] ] 7 => array:3 [ "identificador" => "sec0050" "titulo" => "Renal hypertension in the elderly" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0055" "titulo" => "Demographics" ] 1 => array:3 [ "identificador" => "sec0060" "titulo" => "Anatomical and functional changes of the ageing process" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0065" "titulo" => "Arterial wall modifications" ] 1 => array:2 [ "identificador" => "sec0070" "titulo" => "Endothelial dysfunction" ] 2 => array:2 [ "identificador" => "sec0075" "titulo" => "Changes in neurohormonal regulatory mechanisms" ] ] ] 2 => array:3 [ "identificador" => "sec0080" "titulo" => "Clinical implications" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0085" "titulo" => "Cardiovascular complications" ] 1 => array:2 [ "identificador" => "sec0090" "titulo" => "Impact on neurocognitive functions" ] ] ] 3 => array:3 [ "identificador" => "sec0095" "titulo" => "Treatment" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0100" "titulo" => "Therapeutic targets" ] 1 => array:2 [ "identificador" => "sec0105" "titulo" => "Therapeutic strategies" ] ] ] ] ] 8 => array:2 [ "identificador" => "sec0110" "titulo" => "Funding" ] 9 => array:2 [ "identificador" => "sec0115" "titulo" => "Conflict of interests" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2020-11-11" "fechaAceptado" => "2021-02-04" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1461898" "palabras" => array:5 [ 0 => "Aging" 1 => "Kidney" 2 => "Hypertension" 3 => "Cardiovascular risk" 4 => "CKD" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1461899" "palabras" => array:5 [ 0 => "Envejecimiento" 1 => "Riñón" 2 => "HTA" 3 => "Riesgo cardiovascular" 4 => "ERC" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "Individuals over 65 years are the fastest expanding population throughout the world, due to the increase in human life expectancy. This growing geriatric population, with increasingly associated chronic diseases, has relevant medical, social, and economic impact. Aging is characterized by progressive structural and functional changes in the kidney and in the cardiovascular system, leading to decline in renal function and hypertension. The purpose of this review is to describe the aging-related renal changes and blood pressure regulation during the aging process and their impact with regards to morbidity and mortality in these patients. And to summarize the most appropriate therapeutic approaches in these situations based on the particularities of this population group." ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "Con el incremento de la esperanza de vida de la población, las personas mayores de 65 años son un grupo cada vez más prevalente, con el consiguiente aumento de patologías crónicas asociadas, desencadenando un escenario de gran impacto sociosanitario. Durante el proceso de envejecimiento, se producen cambios tanto estructurales como funcionales en el riñón y en el sistema cardiovascular, que condicionan la aparición de alteraciones de la función renal e HTA, problemas de salud de primer orden en la actualidad. El objetivo de esta revisión es describir los cambios en la función renal y en la regulación de la presión arterial con el envejecimiento, su impacto clínico, en especial en la morbimortalidad de los individuos, y los enfoques terapéuticos ante estas alteraciones, orientados a las características particulares de este grupo poblacional." ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Bouarich H, Chávez Guillén A, Rodríguez Puyol D. Riñón e hipertensión en el anciano. Med Clin (Barc). 2021. https://doi.org/10.1016/j.medcli.2021.02.008" ] ] "multimedia" => array:4 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1210 "Ancho" => 2333 "Tamanyo" => 236064 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Mechanisms of kidney ageing. An integrated view." ] ] 1 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "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=""><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">Microscopic changes \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">Glomerular \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">Expansion of the mesangial matrix \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">Glomerular basement membrane thickening \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">Glomerular atrophy \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">Increased volume of intact glomeruli \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">Pericapsular fibrosis \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">Podocytopathy \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">Glomerulosclerosis (focal and global) \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">Tubulointerstitial \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">Interstitial fibrosis \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">Tubular atrophy \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">Occurrence of diverticula precursors of simple cysts (distal convoluted tubule and collecting tubule) \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">Vascular \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">Arteriosclerosis of the great renal vessels \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">Intimal fibrosis and hyperplasia of the interlobar arteries \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">Communication between the afferent and efferent arterioles in the juxtaglomerular apparatus \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">Macroscopic changes \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">Decreased renal volume, 10−30% between the ages of 40−80 (at the expense of the cortical volume) \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">Weight loss, 10% per decade \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">Height decrease, 0.5 cm per decade, from the age of 40 \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">Granular renal surface \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">Other structural changes \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">Kidney calcifications \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">Focal cortical scars \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">Fibromuscular dysplasia / Renal arteriosclerosis \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2793277.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Renal structural changes." ] ] 2 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0015" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "GFR: glomerular filtration; ERPF: effective renal plasma flow." "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=""><tbody title="tbody"><tr title="table-row"><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">ERPF reduction, 10% per decade \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">Decreased GFR \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">Impaired ability to store and excrete sodium \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">Decreased potassium excretion \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">Changes in the mechanism of urine concentration and dilution \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">Increased vasoconstriction and decreased vasodilator reserve in the renal vascular bed \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">Decreased renal renin production and generation of natriuretic substances \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">Decreased renal hydroxylation of vitamin D \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">Increased serum erythropoietin levels \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">Decreased renal production of klotho \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2793276.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Renal functional changes." ] ] 3 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0020" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "AAFP: American Academy of Family Physicians; ACC/AHA: American College of Cardiology/American Heart Association; CJC/CCS: Canadian Journal of Cardiology/Canadian Cardiovascular Society; ESH/ESC: European Society of Hypertension/European Society of Cardiology; HTN: hypertension; BP: blood pressure; DBP: diastolic blood pressure; SBP: systolic blood pressure." "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">HTN consensus guidelines \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">Therapeutic targets \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">Age \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">2013 ESH/ESC \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">SBP <150 mmHg \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">>65 yrs of age \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">2017 CJC/CCS \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">SBP <120 mmHg \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">>75 yrs of age \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">2017 ACC/AHA \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">BP <130/80 mmHg \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">>65 yrs of age, not institutionalizedIndividualize in institutionalized patients \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">2017 AAFP \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">PA <150/90 \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">>65 yrs of age \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">2018 ESH/ESC \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">SBP 130-139 mmHgDBP < 80 mmHg \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">>65 yrs of age (according to individual tolerance) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2793275.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Blood pressure therapeutic targets in people over 65 years of age according to the Consensus Guidelines for HTN." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:60 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Prevalence of chronic kidney disease and decreased kidney function in the adult US population: Third National Health and Nutrition Examination Survey" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "J. 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Statistics

Review

Kidney and hypertension in older adults

Riñón e hipertensión en el anciano

Hanane Bouaricha, Alina Chávez Guilléna, Diego Rodríguez Puyola,b,

Corresponding author

drodriguez.hupa@gmail.com

Corresponding author.

a Sección de Nefrología, Hospital Universitario Príncipe de Asturias, Alcalá de Henares, Madrid, Spain

b Departamento de Medicina y Especialidades Médicas, Universidad de Alcalá, IRYCIS, Alcalá de Henares, Madrid, Spain

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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Demographics</span><p id="par0005" class="elsevierStylePara elsevierViewall">Ageing is associated with different degrees of chronic kidney disease &#40;CKD&#41;&#44; although 11&#37; of older patients diagnosed with CKD do not have any underlying nephropathy&#44; suggesting that ageing itself may condition a progressive deterioration of kidney function<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a>&#46; The prevalence of CKD in Spain in those over the age of 65 is above 20&#37;&#44; and approximately 38&#37; of adults over 70 have an estimated glomerular filtration rate &#40;GFR&#41; of less than 60&#160;ml&#47;min&#47;1&#46;73&#160;m<span class="elsevierStyleSup">2</span><a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a>&#46; It is estimated that almost half of people over the age of 75 meet the criteria set by the <span class="elsevierStyleItalic">Kidney Disease Improving Global Outcome</span> &#40;KDIGO&#41; guidelines for a diagnosis of CKD<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a>&#46; The incidence of dialysis initiation has also been shown to increase with age&#46; According to the <span class="elsevierStyleItalic">US Data System</span>&#44; the median age of patients starting dialysis is 65&#160;years&#44; but the fastest growing group is found in those over 75<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a>&#46; The <span class="elsevierStyleItalic">Kidney Disease Outcomes Quality Initiative</span> &#40;KDOQI&#41; guidelines establish a classification of CKD based on the degree of GFR and&#47;or presence of kidney damage signs and consider the different stages of CKD to be valid for people of all ages<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a>&#46; However&#44; there is much debate as to what is the normal range of renal function in the elderly&#44; and whether decreased GFR is due to a physiological ageing process or whether it is due to intrinsic renal disease&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Anatomical and functional changes of the ageing process</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Renal structural changes</span><p id="par0010" class="elsevierStylePara elsevierViewall">The main renal structural changes associated with ageing are quite nonspecific and not always easy to distinguish from the changes produced by other processes&#44; such as arterial hypertension &#40;HTN&#41; or diabetes &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; Perhaps the most characteristic features are the progressive decrease in renal volume&#44; estimated to be around 10&#37; per decade from the fourth decade of life onwards&#44; the decrease in the number of intact glomeruli&#44; which in turn appear hypertrophic&#44; glomerular sclerosis and interstitial fibrosis<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6&#44;7</span></a>&#46; The earliest descriptions of nephron mass reduction with ageing are quite old and come from autopsy studies&#46; Recently&#44; Denic et al&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> showed that the number of intact glomeruli decreases from approximately one million in the second decade of life to 600&#44;000 in the eighth decade&#44; with an increase in histologically detectable sclerosed glomeruli of up to 10&#37; and a statistically significant negative relationship between the number of glomeruli and their volume<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a>&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Renal functional changes</span><p id="par0015" class="elsevierStylePara elsevierViewall">The GFR decreases with age&#44; but several studies question whether there is an unambiguous relationship between age and the decrease in GFR&#46; The <span class="elsevierStyleItalic">Baltimore Longitudinal Study on Ageing</span>&#44; in a group of 254 people with a 24&#160;year follow-up&#44; without HTN or other causes of CKD showed that the mean decrease in GFR was 0&#46;75&#160;ml&#47;min&#47;year&#44; a third of the individuals had their GFR completely stable&#44; and even a small group showed a small increase in GFR<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a>&#46; Other longitudinal studies have confirmed similar results&#44; estimating that the reduction in GFR with age can range from 0&#46;4&#160;ml&#47;min to 3&#46;8&#160;ml&#47;min per year<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10&#44;11</span></a>&#46; This variability lies in the different rate of nephron loss in different individuals&#44; but also in the adaptive capacity of intact glomeruli&#46; In fact&#44; the glomeruli of aged kidneys behave like hyperfiltrating glomeruli&#44; with a dissociation between anatomical changes and loss of function &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a>&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">Ageing is characterised by progressive tubular dysfunction&#46; Basically&#44; the elderly patient usually maintains a sodium balance similar to that of young patients&#59; however&#44; in situations of volume depletion the response to the reduction in sodium excretion is significantly slower&#46; This phenomenon contributes to the susceptibility of the elderly to the development of acute renal failure &#40;ARF&#41;&#46; Potassium excretion is decreased by a reduction in the transtubular potassium gradient&#44; the presence of a certain degree of hyporeninaemic hypoaldosteronism and a decrease in the sodium load reaching the distal nephron in situations of volume depletion&#46; This somewhat explains the predisposition to drug-induced hyperkalaemia in elderly patients<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a>&#46; The urine concentration and dilution mechanism is also altered&#44; explaining the high incidence of nocturia&#44; the predisposition to dehydration and hypernatremia in cases of low intake&#44; and hyponatremia when excess fluids are administered<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">13&#44;14</span></a>&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">With age&#44; renal renin production decreases&#44; contributing to a reduction in plasma renin activity and&#44; therefore&#44; angiotensin II and aldosterone synthesis&#44; with their respective impact on electrolyte homeostasis and blood volume<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a>&#46; The generation of natriuretic substances such as PGE<span class="elsevierStyleInf">2</span> and dopamine is reduced&#44; increasing sensitivity to salt<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a>&#46; Plasma levels of 1&#44;25-dihydroxyvitamin D are generally in the low-normal range&#44; indicating a decrease in renal hydroxylation of vitamin D<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a>&#46; Serum erythropoietin increases with age&#44; due to a complex mechanism that is not entirely well defined<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a>&#46; Finally&#44; renal formation of klotho&#44; a cofactor of FGF23 to which systemic actions are attributed&#44; decreases with age&#44; which may contribute to ageing in other parts of the body<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a>&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Mechanisms involved in kidney ageing</span><p id="par0030" class="elsevierStylePara elsevierViewall">Transcriptome analysis of aged kidneys has identified overexpression of genes related to extracellular matrix synthesis and inflammation<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a>&#46; These two factors play a key role in the development of renal structural and functional alterations with ageing&#44; but they are only the final common pathway of a process that is actively being studied &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; The molecular basis of the renal ageing phenomenon includes cellular senescence&#44; which includes genomic instability&#44; loss of telomeres and DNA repeats at the end of chromosomes as a result of loss of telomerase activity&#44; chronic oxidative damage contributing to telomeric shortening resulting in the senescent phenotype&#44; a certain genetic programming favouring accelerated cellular ageing&#44; with subsequent inflammatory phenotype&#44; thus inducing changes in the kidney<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">20&#44;21</span></a> and finally cell death&#46; This cell damage is essentially determined by chronic inflammation and cellular senescence&#46; The accumulation of non-dividing senescent cells can compromise the tissue&#39;s capacity for renewal and repair&#46; In addition&#44; certain genes that are overexpressed by the senescent response may encode for soluble proteins &#40;cytokines&#44; adhesion molecules and growth factors&#41; that can alter the tissue microenvironment&#44; thereby altering its structure and function<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">22&#8211;24</span></a>&#46; Along with this&#44; environmental and hormonal factors can also influence genetic determinants&#44; affecting renal behaviour in old age &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Clinical implications</span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Glomerular filtration rate measurement in clinical practice</span><p id="par0035" class="elsevierStylePara elsevierViewall">In clinical practice&#44; the quantification of renal function often uses formulae developed to estimate GFR from serum creatinine and physical and laboratory parameters&#44; all of which have a certain degree of inaccuracy and are not validated in individuals over 70&#160;years of age&#46; The most accurate and the one most used today is the <span class="elsevierStyleItalic">Chronic Kidney Disease Epidemiology Collaboration</span> &#40;CKD-EPI&#41;&#44; created in 2009<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a>&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Clinical guidelines define CKD as the presence for at least 3&#160;months of a GFR of less than 60&#160;ml&#47;min&#47;1&#46;73&#160;m<span class="elsevierStyleSup">2</span> or evidence of structural or functional renal abnormalities other than GFR<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;5</span></a>&#46; It is these abnormalities that should be evaluated in the elderly and&#44; in their absence&#44; moderate reductions in GFR should not be considered pathological&#44; although they should be considered when administering drugs&#46; In summary&#44; we could conclude that individuals over the age of 75 with a GFR above 45&#160;ml&#47;min&#47;1&#46;73&#160;m<span class="elsevierStyleSup">2</span> and without other renal abnormalities should not be considered nephrological patients&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Clinical problems associated with kidney dysfunction</span><p id="par0045" class="elsevierStylePara elsevierViewall">The reduction in renal haemodynamic and functional reserve that occurs with ageing may compromise the organ&#39;s adaptation to acute ischaemia or following exposure to nephrotoxic drugs&#44; increasing susceptibility to ARF&#46; The existence of previous CKD has been described as the greatest risk factor for developing ARF&#46; Thus&#44; the risk doubles for GFR between 45-59&#160;ml&#47;min compared to GFR &#62;&#160;60&#160;ml&#47;min<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a>&#46; Proteinuria also seems to double the risk of ARF regardless of GFR<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a>&#46; Other factors&#44; such as the higher prevalence of certain comorbidities in the elderly&#44; polypharmacy&#44; and the fact that certain procedures &#40;contrasts&#44; surgical interventions&#41; are performed more often in this population group&#44; may also contribute to increasing the incidence of ARF<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a>&#46; It should be underlined that age over 65 is a risk factor for progression to CKD after an episode of ARF&#46; A meta-analysis reveals that 31&#37; of patients &#62;65 did not recover their previous kidney function after an episode of ARF compared to 26&#37; in younger patients<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a>&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">As in younger people&#44; the presence of CKD in the elderly can be associated with a number of complications&#46; In general&#44; the clinical manifestations of CKD develop progressively&#44; with great variability from patient to patient&#44; depending on the rate of progression and the amount of functioning renal mass&#46; A GFR of less than 30&#160;ml&#47;min usually signals the borderline at which CKD becomes symptomatic&#44; after which a wide range of clinical manifestations develop in parallel with the progressive stage&#44; including water and sodium metabolism disorders&#44; which can lead to heart failure &#40;HF&#41;&#44; HTN&#44; oedema and hyponatraemia&#59; electrolyte disturbances&#44; with hyperkalaemia being the most relevant&#44; bone-mineral metabolism disturbances with the occurrence of hypocalcaemia and hyperphosphatemia&#44; responsible for the pruritus typical of CKD&#46; Metabolic acidosis&#44; normocytic normochromic anaemia&#44; altered lipid profile with elevated triglycerides and LDL cholesterol may also occur together with low HDL cholesterol levels&#44; glucose intolerance&#44; hyperuricemia&#44; and increased bleeding time due to platelet dysfunction&#44; thus increasing the risk of bleeding in these patients<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;5</span></a>&#46; Intervention on these complications of CKD should be individualised according to functional status&#44; accompanying symptoms and disease progression&#46; The ideal treatment should be aimed at improving the patient&#39;s quality of life rather than addressing isolated laboratory figures&#46; Adequate control of cardiovascular risk factors&#44; anaemia&#44; acidosis&#44; and malnutrition are key to achieving this effect&#46; It should be noted that&#44; in the elderly patient&#44; the clinical symptoms of CKD are often absent and that in many cases the casual finding of elevated urea and creatinine levels points to the diagnosis&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">The factors for progression of CKD in the elderly patient are the classic ones described for the general population plus hyperfiltration&#46; It is therefore recommended to correct modifiable risk factors and to intervene on the glomerular overload caused by the reduction in renal mass&#46; In this sense&#44; adequate control of blood pressure levels&#44; also modifying intrarenal hemodynamics by blocking angiotensin&#44; is essential to prevent the potential reduction in GFR&#46; Proteinuria is a clinical marker that must be considered&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Medication dose adjustment to glomerular filtration rate</span><p id="par0060" class="elsevierStylePara elsevierViewall">One of the greatest consequences of ageing is the increased susceptibility to drug toxicity&#46; Decreasing renal excretory capacity and&#44; to a lesser extent&#44; changes in hepatic metabolism and changes in body composition that occur with age&#44; contribute to changes in the pharmacokinetics of many drugs<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a>&#46; The same is true for the pharmacodynamics of many drugs&#58; age regulates the sensitivity and physiological response to their actions&#46; When polypharmacy and polypathology are added to this&#44; the medication dose adjustment becomes a complex problem&#46; It is recommended to adjust the dose to the estimated renal function&#44; whether it is a patient with a diagnosis of CKD or a decrease in GFR associated with ageing&#46;</p></span></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Renal hypertension in the elderly</span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Demographics</span><p id="par0065" class="elsevierStylePara elsevierViewall">HTN is one of the most prevalent diseases in the world today&#46; Its global prevalence in developed countries is around 25&#37;&#44; while in the elderly it can be 60&#8211;80&#37;&#46; With an estimated 4&#46;4&#37; of the world&#39;s population being over 80&#160; years of age by 2050&#44; the global prevalence of HTN will increase steadily over the next few years<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a>&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">During the ageing process&#44; various structural and functional changes and modifications occur in the cardiovascular system that favour an increase in systolic blood pressure &#40;SBP&#41;&#46; This increase is evidenced in 65&#37; of patients over the age of 60 and in 90&#37; of those over 70&#44; with a higher incidence in women&#46; Systolic HTN is associated with a significant increase in cardiovascular risk<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a>&#46; Diastolic blood pressure &#40;DBP&#41;&#44; however&#44; undergoes a reverse process&#44; starting to decline from the age of 50 in both sexes&#44; with a consequent increase in pulse pressure &#40;PP&#41;&#46; PP is defined as the difference between SBP and DBP and is a powerful predictor for the development of cardiovascular events<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a>&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Anatomical and functional changes of the ageing process</span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Arterial wall modifications</span><p id="par0075" class="elsevierStylePara elsevierViewall">The changes associated with ageing that favour an increase in blood pressure &#40;BP&#41; generally have to do with the changes our body undergoes with age&#46; Environmental factors linked to the lifestyle habits of each individual&#44; such as salt intake&#44; smoking and overweight&#44; as well as genetic factors&#44; also play a role&#46; The most characteristic and significant structural change that occurs with ageing is a loss of elasticity and distensibility of the great arteries&#44; with an increase in their stiffness and a decrease in their capacitance&#44; which determines an impairment to buffer the pressure generated from the left ventricle&#44; thus leading to a progressive increase in SBP&#46; When these same changes take place in the arteries of medium and small calibre&#44; what occurs is an increase in peripheral resistance&#44; increasing DBP<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">34</span></a>&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Structural changes in the arterial wall are involved in the etiopathogenesis of these processes&#44; especially in its intima and media layers&#46; The arterial media layer is made up of smooth muscle cells surrounded by extracellular matrix&#44; which in turn is made up of collagen and elastin&#46; With age&#44; the endothelium becomes more permeable to the passage of macromolecules and the deposits of calcium&#44; phospholipids and cholesterol esters increase&#46; The elastic fibres of the internal elastic lamina lose their elasticity and their degradation is accelerated by an increase in the activity of elastases&#46; There is an expansion of the extracellular matrix by deposition of collagen&#44; elastin and proteoglycans and hypertrophy and hyperplasia of smooth muscle cells<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a>&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Endothelial dysfunction</span><p id="par0085" class="elsevierStylePara elsevierViewall">Arterial stiffness is not only a consequence of structural changes in the vascular wall&#44; but also depends on changes in the synthesis of vasoactive endothelial mediators&#46; During ageing&#44; endothelium-dependent vascular functions are altered&#44; a phenomenon called endothelial dysfunction&#44; which is characterised by an imbalance between the synthesis and release of vasodilator and vasoconstrictor substances&#44; especially affecting the nitric oxide &#40;NO&#41;-dependent vasodilator response and favouring vasoconstriction and increased peripheral vascular resistances<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">36&#44;37</span></a>&#46; In turn&#44; NO deficiency negatively influences leukocyte adhesion&#44; platelet aggregation and smooth muscle cell proliferation&#44; thus contributing to the development of atherosclerosis&#46; In addition&#44; the endothelial secretion of certain substances&#44; such as interleukins&#44; endothelin&#44; or <span class="elsevierStyleItalic">insulin growth factor</span> 1&#44; would also favour the formation of collagen matrix in the arterial wall<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">38</span></a>&#46; Data from experimental and clinical studies link elevated levels of asymmetric dimethylarginine &#40;ADMA&#41;&#44; together with reduced NO bioavailability&#44; to the endothelial dysfunction observed in HTN in the elderly<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">39</span></a>&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Changes in neurohormonal regulatory mechanisms</span><p id="par0090" class="elsevierStylePara elsevierViewall">An increase in angiotensin II&#44; angiotensin converting enzyme and mineralocorticoid receptor levels is observed in ageing&#46; Elevated levels of these factors stimulate extracellular matrix production and result in the development of inflammation&#44; oxidative stress&#44; and fibrosis&#44; thus contributing to the arterial stiffness seen with age&#46; Evidence from recent years points to the renin&#47;prorenin receptor and its profibrosing role as another angiotensin II independent pathway to increase extracellular matrix<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a>&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">The role of the sympathetic nervous system in the maintenance of hypertension in humans is well known&#46; Circulating catecholamine levels increase with age&#44; more in women than in men&#44; generally after the age of 40&#46; However&#44; beta-adrenergic vasodilation of vascular smooth muscle decreases with ageing due to a decrease in both the number and affinity of beta receptors&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">In the autonomic nervous system&#44; age-related reduction in baroreceptor function contributes to the high prevalence of orthostatic hypotension&#46; It has also been shown that arterial stiffness alters the homeostatic mechanism responsible for maintaining the stability of BP and tissue perfusion during different physiological conditions&#44; such as orthostatism&#44; exercise&#44; postpartum or stress&#44; thus conditioning a great variability of SBP in these situations <a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">41</span></a>&#46;</p></span></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Clinical implications</span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Cardiovascular complications</span><p id="par0105" class="elsevierStylePara elsevierViewall">In the elderly&#44; isolated systolic HTN is the most prevalent form of HTN&#46; There are numerous studies that relate it to an increase in cardiovascular morbidity and mortality&#46; The Framingham study&#44; with a follow-up of more than 30&#160;years&#44; found that patients with isolated systolic HTN had an increased risk of death from cardiovascular disease of 1&#46;8 in males and 4&#46;7 in females<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">42</span></a>&#46; Another epidemiological study&#44; the <span class="elsevierStyleItalic">Multiple Risk Factor Intervention Trial</span> &#40;MRFIT&#41;&#44; with a follow-up of more than 300&#44;000 individuals over 10&#160;years&#44; also evidenced a significant increase in cardiovascular mortality linked to SBP values<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">43</span></a>&#46; Other studies&#44; on the other hand&#44; suggest that BP has a limited predictive value for total mortality after the age of 70&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">The prevalence of coronary heart disease is higher in hypertensive than in normotensive elderly&#44; although this difference becomes less pronounced with every decade of increase&#46; Left ventricular hypertrophy &#40;LVH&#41; and cardiac diastolic dysfunction are quite common in these patients&#44; and it is possible that this difficulty in cardiac filling is primarily responsible for the low cardiac output and the development of HF<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">44</span></a>&#46; Atrial fibrillation clearly increases its incidence in hypertensive elderly patients and has been associated with an increased risk of cardiovascular events&#44; stroke&#44; and impaired kidney function&#46; HTN&#44; age&#44; and proteinuria have a negative impact on the course of CKD&#44; which in turn is associated with increased cardiovascular risk&#46; SBP is an independent marker of worsening kidney function in the elderly with isolated systolic HTN&#46; Regarding the risk of cerebrovascular disease &#40;CVD&#41;&#44; the association of HTN and ischemic or hemorrhagic CVD increases with age&#44; with isolated systolic HTN being an important risk factor&#46;</p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Impact on neurocognitive functions</span><p id="par0115" class="elsevierStylePara elsevierViewall">Numerous observational studies have documented the association between elevated BP levels in middle-aged people and the risk of vascular dementia and Alzheimer&#39;s disease&#46; This relationship was first observed in the Framingham study&#44; in which elevated BP levels detected in the previous 20&#160;years had an inverse correlation with cognitive status in untreated hypertensive patients<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">42</span></a>&#46; Since this initial observation&#44; there have been numerous epidemiological studies that have verified this association between hypertension and cognitive impairment<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">45</span></a>&#46; Others&#44; however&#44; have not demonstrated this association&#44; observing discrepancies between the results of various studies&#46; The same occurs with the results of the studies that analysed the decrease in the incidence of dementia with antihypertensive treatment&#46; While the Syst-Eur and PROGRESS studies showed a decrease in the incidence of dementia in the treatment group<a class="elsevierStyleCrossRefs" href="#bib0230"><span class="elsevierStyleSup">46&#44;47</span></a>&#44; in the SCOPE&#44; SHEP and HYVET studies these differences were not significant<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">48&#8211;50</span></a>&#46;</p></span></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Treatment</span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Therapeutic targets</span><p id="par0120" class="elsevierStylePara elsevierViewall">Until relatively recently&#44; it was not clear whether or not to treat hypertension in the elderly&#46; Currently&#44; there is sufficient evidence on the benefit of hypertension management in the elderly population&#44; at least in terms of cardiovascular morbidity and mortality since there does not seem to be a clear impact on cognitive functions&#46; A Cochrane review of 12 clinical trials showed that adequate management of hypertension in people over 60&#160;years of age was associated with a reduction in mortality&#46; Another review of 5 clinical trials by MacMahon and Rodgers<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">51</span></a> on antihypertensive treatment and reduction of cardiovascular morbidity and mortality in the elderly demonstrated a reduction in stroke incidence of 34&#37;&#44; in coronary events of 19&#37; and in overall cardiovascular mortality of 23&#37;&#46; These results were observed with a reduction of 12&#8722;14&#160;mmHg in SBP and 5&#8722;6&#160;mmHg in DBP&#44; with a follow-up period of 5&#160;years&#46; Other intervention studies carried out in the elderly population have also shown the benefit of treating both HTN and isolated systolic HTN<a class="elsevierStyleCrossRefs" href="#bib0230"><span class="elsevierStyleSup">46&#8211;49</span></a>&#46; Thus&#44; octogenarians in the HYVET study showed a 30&#37; reduction in the rate of stroke&#44; a 64&#37; decrease in HF episodes and a 21&#37; decrease in the occurrence of major cardiovascular events and all-cause mortality<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">50</span></a>&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">It is difficult to find consensus on BP target in the different guidelines for the management of HTN in the elderly&#46; <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> tries to summarize the opinions of the different scientific societies<a class="elsevierStyleCrossRefs" href="#bib0260"><span class="elsevierStyleSup">52&#8211;56</span></a>&#46; In general&#44; there is a tendency to recommend increasingly intensive BP monitoring&#46; However&#44; the therapeutic target must be individualized according to the clinical characteristics of each patient and the individual tolerance to the decrease in BP levels&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span><span id="sec0105" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Therapeutic strategies</span><p id="par0130" class="elsevierStylePara elsevierViewall">As in any patient with essential HTN&#44; lifestyle modifications are the first step to consider in the treatment of hypertensive older people&#46; The measures are the same as those suggested in other populations&#44; and the TONE study has confirmed their usefulness<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">57</span></a>&#46; Perhaps special attention should be paid to weight loss&#44; as potential loss of muscle mass is not advisable in older people&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">Drug therapy must be started after failure of lifestyle modification measures and must be individualized&#44; choosing the drug that best controls BP and with the fewest side effects&#46; It is important to bear in mind a number of clinical aspects specific to this group of patients&#44; such as age-related physiological changes&#44; the presence of comorbidities&#44; common polypharmacy&#44; and cognitive function&#46; In this sense&#44; the studies that have analysed aspects of quality of life have ruled out any negative impact with antihypertensive treatment in this population&#44; although some drugs may have a negative impact&#44; such as beta-blockers&#44; which in the TONE study were associated with major depressive symptoms&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">In view of the experience accumulated in the various published clinical trials&#44; most international guidelines propose the same antihypertensive drugs that are used in young patients and that include the main therapeutic groups&#58; thiazide diuretics&#44; calcium channel blockers&#44; angiotensin converting enzyme inhibitors &#40;ACEI&#41;&#44; angiotensin II receptor blockers &#40;ARBs&#41; and beta-blockers&#46; The American guidelines do not specifically recommend any drug in the antihypertensive treatment of patients over 60<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">54</span></a>&#46; The British <span class="elsevierStyleItalic">National Institute for Health Care Excellence</span> &#40;NICE&#41; guidelines do not include beta-blockers as the first line of treatment in older patients<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">58</span></a>&#46; European guidelines favour the use of calcium channel blockers or thiazide diuretics in the absence of comorbidities that determine the use of other antihypertensives<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">56</span></a>&#46; Recently&#44; based on the results of different studies&#44; it has been proposed that patients over 80 years of age should be prescribed ACEI or ARBs among the first-line drugs<a class="elsevierStyleCrossRefs" href="#bib0260"><span class="elsevierStyleSup">52&#8211;57</span></a>&#46; The use of alpha blockers as first-line therapeutic agents is not generally recommended&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">A significant percentage of older patients develop mainly systolic hypertension&#44; with a significant increase in PP&#44; responding inadequately to the above therapies and presenting extemporaneous elevations of their SBP&#44; often related to emotional or physical stress&#44; leading to recurrent emergency interventions&#46; It should be remembered the stiffness of the large central thoracic arteries is critical in the genesis of the condition in these patients&#44; and that the elasticity of these arteries cannot be restored&#46; In these patients&#44; consideration should be given to the appropriate use of drugs to reduce cardiac output&#44; which&#44; together with the capacitance of the great arteries&#44; is responsible for SBP&#46; Drugs such as diuretics or beta-blockers may be useful in treating these patients but should be used with caution because of possible side effects&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">It is worth noting that a new approach to the management of HTN is becoming increasingly relevant&#44; with a focus on making nocturnal blood pressure a validated therapeutic target&#46; Different studies have confirmed that nocturnal blood pressure is the best indicator of cardiovascular and cerebrovascular risk and that reducing it increases survival &#40;MAPEC&#44; <span class="elsevierStyleItalic">The Hygia Chronotherapy Trial</span>&#44; <span class="elsevierStyleItalic">HOPE</span>&#44; <span class="elsevierStyleItalic">The Syst&#46;Eur trial</span>&#41;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">59</span></a>&#46; The study by Hermida et al&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">60</span></a> provides robust evidence on the safety and efficacy of the nocturnal strategy of antihypertensive treatment and reinforces the importance of adequate blood pressure control on long-term prognosis&#44; with promising results on cardiovascular benefits that translate into a reduction of cardiovascular and cerebrovascular risk by 50&#8211;60&#37;&#44; with this benefit being maintained in renal patients&#46; The study also endorses ambulatory blood pressure monitoring &#40;ABPM&#41; as the best tool for the diagnosis of hypertension and for predicting the risk of heart attack and stroke and justifies its routine use in the clinic&#46;</p></span></span></span><span id="sec0110" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Funding</span><p id="par0155" class="elsevierStylePara elsevierViewall">The project has been financed with funds from the <span class="elsevierStyleGrantSponsor" id="gs0005">Carlos III Health Institute</span> &#40;<span class="elsevierStyleGrantNumber" refid="gs0005">PI17&#47;01513</span>&#44; <span class="elsevierStyleGrantNumber" refid="gs0005">RD16&#47;0009&#47;0018</span>&#41; and of the <span class="elsevierStyleGrantSponsor" id="gs0010">Community of Madrid</span> &#40;NOVELREN-CM&#47;CLINIREN&#41;&#46;</p></span><span id="sec0115" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Conflict of interests</span><p id="par0160" class="elsevierStylePara elsevierViewall">The authors declare no conflict of interest&#46;</p></span></span>"
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              "identificador" => "sec0025"
              "titulo" => "Mechanisms involved in kidney ageing"
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              "titulo" => "Anatomical and functional changes of the ageing process"
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                0 => array:2 [
                  "identificador" => "sec0065"
                  "titulo" => "Arterial wall modifications"
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                  "titulo" => "Endothelial dysfunction"
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                  "identificador" => "sec0075"
                  "titulo" => "Changes in neurohormonal regulatory mechanisms"
                ]
              ]
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                0 => array:2 [
                  "identificador" => "sec0085"
                  "titulo" => "Cardiovascular complications"
                ]
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                  "identificador" => "sec0090"
                  "titulo" => "Impact on neurocognitive functions"
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              ]
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              "identificador" => "sec0095"
              "titulo" => "Treatment"
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                  "titulo" => "Therapeutic targets"
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                  "titulo" => "Therapeutic strategies"
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          "titulo" => "Funding"
        ]
        9 => array:2 [
          "identificador" => "sec0115"
          "titulo" => "Conflict of interests"
        ]
        10 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2020-11-11"
    "fechaAceptado" => "2021-02-04"
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        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec1461898"
          "palabras" => array:5 [
            0 => "Aging"
            1 => "Kidney"
            2 => "Hypertension"
            3 => "Cardiovascular risk"
            4 => "CKD"
          ]
        ]
      ]
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          "titulo" => "Palabras clave"
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          "palabras" => array:5 [
            0 => "Envejecimiento"
            1 => "Ri&#241;&#243;n"
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      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Individuals over 65 years are the fastest expanding population throughout the world&#44; due to the increase in human life expectancy&#46; This growing geriatric population&#44; with increasingly associated chronic diseases&#44; has relevant medical&#44; social&#44; and economic impact&#46; Aging is characterized by progressive structural and functional changes in the kidney and in the cardiovascular system&#44; leading to decline in renal function and hypertension&#46; The purpose of this review is to describe the aging-related renal changes and blood pressure regulation during the aging process and their impact with regards to morbidity and mortality in these patients&#46; And to summarize the most appropriate therapeutic approaches in these situations based on the particularities of this population group&#46;</p></span>"
      ]
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Con el incremento de la esperanza de vida de la poblaci&#243;n&#44; las personas mayores de 65 a&#241;os son un grupo cada vez m&#225;s prevalente&#44; con el consiguiente aumento de patolog&#237;as cr&#243;nicas asociadas&#44; desencadenando un escenario de gran impacto sociosanitario&#46; Durante el proceso de envejecimiento&#44; se producen cambios tanto estructurales como funcionales en el ri&#241;&#243;n y en el sistema cardiovascular&#44; que condicionan la aparici&#243;n de alteraciones de la funci&#243;n renal e HTA&#44; problemas de salud de primer orden en la actualidad&#46; El objetivo de esta revisi&#243;n es describir los cambios en la funci&#243;n renal y en la regulaci&#243;n de la presi&#243;n arterial con el envejecimiento&#44; su impacto cl&#237;nico&#44; en especial en la morbimortalidad de los individuos&#44; y los enfoques terap&#233;uticos ante estas alteraciones&#44; orientados a las caracter&#237;sticas particulares de este grupo poblacional&#46;</p></span>"
      ]
    ]
    "NotaPie" => array:1 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Bouarich H&#44; Ch&#225;vez Guill&#233;n A&#44; Rodr&#237;guez Puyol D&#46; Ri&#241;&#243;n e hipertensi&#243;n en el anciano&#46; Med Clin &#40;Barc&#41;&#46; 2021&#46; <span class="elsevierStyleInterRef" id="intr0005" href="https://doi.org/10.1016/j.medcli.2021.02.008">https&#58;&#47;&#47;doi&#46;org&#47;10&#46;1016&#47;j&#46;medcli&#46;2021&#46;02&#46;008</span></p>"
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                  <table border="0" frame="\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Microscopic changes</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Glomerular</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Expansion of the mesangial matrix&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Glomerular basement membrane thickening&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Glomerular atrophy&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Increased volume of intact glomeruli&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Pericapsular fibrosis&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Podocytopathy&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Occurrence of diverticula precursors of simple cysts &#40;distal convoluted tubule and collecting tubule&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Intimal fibrosis and hyperplasia of the interlobar arteries&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Communication between the afferent and efferent arterioles in the juxtaglomerular apparatus&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Decreased renal volume&#44; 10&#8722;30&#37; between the ages of 40&#8722;80 &#40;at the expense of the cortical volume&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Height decrease&#44; 0&#46;5&#160;cm per decade&#44; from the age of 40</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">ERPF reduction&#44; 10&#37; per decade&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Impaired ability to store and excrete sodium&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">Decreased potassium excretion&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">Changes in the mechanism of urine concentration and dilution&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
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                  \t\t\t\t">Increased vasoconstriction and decreased vasodilator reserve in the renal vascular bed&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">Decreased renal renin production and generation of natriuretic substances&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">Decreased renal hydroxylation of vitamin D&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">Increased serum erythropoietin levels&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">Decreased renal production of klotho&nbsp;\t\t\t\t\t\t\n
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          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Renal functional changes&#46;</p>"
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                  \t\t\t\t">2013 ESH&#47;ESC&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">SBP &#60;150&#160;mmHg&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#62;65&#160;yrs of age&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2017 CJC&#47;CCS&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">SBP &#60;120&#160;mmHg&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#62;75&#160;yrs of age&nbsp;\t\t\t\t\t\t\n
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                  \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">2017 ACC&#47;AHA&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">BP &#60;130&#47;80&#160;mmHg&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
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                  \t\t\t\t">&#62;65&#160;yrs of age&#44; not institutionalizedIndividualize in institutionalized patients&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">2017 AAFP&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">PA &#60;150&#47;90&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#62;65&#160;yrs of age &#40;according to individual tolerance&#41;&nbsp;\t\t\t\t\t\t\n
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                            2 => "X&#46; Yu"
                            3 => "R&#46; Saxena"
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                  ]
                  "host" => array:1 [
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