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Ácido úrico y daño renal agudo en pacientes con alto riesgo de desarrollar daño renal agudo sometidos a cirugía cardiaca: cohorte prospectiva multicéntrica
Uric Acid and acute kidney injury in high-risk patients for developing Acute Kidney Injury undergoing cardiac surgery: a prospective multicenter study
D. Nagorea,d, A. Candelaa,b, M. Bürgec, E. Tamayod, M. Murie-Fernándeze, M. Vivesg,f,
Autor para correspondencia
mvives@unav.es

Autor para correspondencia.
, P. Monederog, J. Álvarezh, E. Mendezi, A. Pasqualettoi, T. Moni, R. Pitaj, M.A. Varelaj, C. Estevaj, M.A. Pereiraj, J. Sanchezk, M.A. Rodriguezk, A. Garcial, P. Carmonam, M. Lópezm..., A. Pajaresm, R. Vicentem, R. Apariciom, I. Grageran, E. Calderóno, J.M. Marcosp, L. Gómezq, J.M. Rodríguezr, A. Matillar, A. Medinas, A. Hernándezt, L. Moralesu, L. Santanau, E. Garciav, S. Montesinosw, P. Muñozx, B. Bravoy, V. Blancoaa, y en nombre del Grupo Español de Investigación en Cirugía Cardiaca Perioperatoria Ver más
a Departamento de Anestesia y Medicina Perioperatoria, Grupo Quirón - Policlínica Guipúzcoa, San Sebastián, España
b Departamento de Anestesiología y Medicina Perioperatoria, Hospital Universitario Ramón y Cajal, Madrid, España
c Departamento de Anestesia y Medicina Perioperatoria, Barts Heart Centre, St Bartholomew's Hospital, Londres, Reino Unido
d Departamento de Anestesiología y Medicina Perioperatoria, Hospital Clínico Universitario de Valladolid, Valladolid, España
e Departamento de Neurología, Clínica San Miguel, Pamplona, España
f Departamento de Anestesiología y Cuidados Intensivos, Clínica Universidad de Navarra, Pamplona, España
g Departamento de Anestesiología & Cuidados Intensivos, Clínica Universidad de Navarra, Pamplona, España
h Departamento de Anestesiología y Medicina Perioperatoria, Complejo Hospitalario Universitario de Santiago de Compostela, Santiago de Compostela, España
i Departamento de Anestesiología y Medicina Perioperatoria, Hospital Universitario de Bellvitge, L’Hospitalet de Llobregat, Barcelona, España
j Departamento de Anestesiología y Medicina Perioperatoria, Hospital Alvaro Cunqueiro Vigo, Vigo, España
k Departamento de Anestesiología y Medicina Perioperatoria, Hospital Universitario Central de Asturias, Oviedo, España
l Departamento de Anestesiología y Medicina Perioperatoria, Hospital Universitari Vall d’Hebron, Barcelona, España
m Departamento de Anestesiología y Medicina Perioperatoria, Hospital Universitari i Politécnic La Fe, Valencia, España
n Departamento de Anestesiología y Medicina Perioperatoria, Hospital Infanta Cristina, Badajoz, España
o Departamento de Anestesiología y Medicina Perioperatoria, Hospital Universitario Puerta de Mar, Cádiz, España
p Departamento de Anestesiología y Medicina Perioperatoria, Hospital Universitario de León, León, España
q Departamento de Anestesiología y Medicina Perioperatoria, Hospital Universitario Virgen del Rocio, Sevilla, España
r Departamento de Anestesiología y Medicina Perioperatoria, Hospital Universitario de Salamanca, Salamanca, España
s Departamento de Anestesiología y Medicina Perioperatoria, Hospital Universitario de Málaga, Málaga, España
t Departamento de Anestesiología y Medicina Perioperatoria, Hospital Policlínica Ibiza, Ibiza, España
u Servicio de Anestesiología y Medicina Perioperatoria, Hospital Universitario Dr, Negrín, Las Palmas de Gran Canaria, España
v Departamento de Anestesiología y Medicina Perioperatoria, Hospital Clínico Universitario de Valencia, Valencia, España
w Departamento de Anestesiología y Medicina Perioperatoria, Centro Médico Teknon Barcelona, Barcelona, España
x Departamento de Anestesiología y Medicina Perioperatoria, Hospital 12 de octubre, Madrid, España
y Servicio de Anestesiología y Medicina Perioperatoria, Hospital de Cruces de Bizkaia, Bilbao, España
aa Departamento de Anestesiología y Medicina Perioperatoria, Hospital Universitario Virgen de la Macarena, Sevilla, España
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Introducci&#243;n</span><p id="par0020" class="elsevierStylePara elsevierViewall">El da&#241;o renal agudo &#40;DRA&#41; posoperatorio es frecuente tras la cirug&#237;a cardiaca &#40;DRA-CS&#41;&#46; Se asocia a un empeoramiento de los resultados cl&#237;nicos y la supervivencia a corto y largo plazo&#44; as&#237; como a un aumento de los costes para el paciente<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">1&#8211;3</span></a>&#46; Dado el gran n&#250;mero de intervenciones de cirug&#237;a cardiaca que se realizan anualmente en todo el mundo &#40;m&#225;s de un mill&#243;n de intervenciones&#41;&#44; se trata de un problema sanitario importante<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">4</span></a>&#46; Los modelos predictivos que estiman el riesgo de DRA de los pacientes pueden ser &#250;tiles para optimizar los cuidados perioperatorios y prevenir el DRA en estos pacientes&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Cada vez hay m&#225;s pruebas epidemiol&#243;gicas y cl&#237;nicas de que la hiperuricemia&#44; incluso en concentraciones bajas sin causar la precipitaci&#243;n intratubular de cristales&#44; puede desempe&#241;ar un papel en la patog&#233;nesis del DRA<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">5</span></a>&#46; El &#225;cido &#250;rico s&#233;rico &#40;AUS&#41; puede desempe&#241;ar un papel en muchos de los mecanismos propuestos que conducen al DRA&#44; como la inducci&#243;n de la vasoconstricci&#243;n renal<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">6</span></a>&#44; la inflamaci&#243;n&#44; la antiangiog&#233;nesis y el deterioro de la autorregulaci&#243;n<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">7</span></a>&#44; adem&#225;s de desempe&#241;ar funciones importantes en las respuestas inmunitarias tanto adaptativas como innatas<a class="elsevierStyleCrossRefs" href="#bib0190"><span class="elsevierStyleSup">8&#44;9</span></a>&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Un estudio reciente ha evaluado la asociaci&#243;n entre las concentraciones preoperatorias elevadas de AUS y el desarrollo de DRA posoperatoria en una cohorte de pacientes sometidos a cirug&#237;a cardiaca<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">10</span></a>&#46; Los datos de este estudio mostraron que la hiperuricemia preoperatoria estaba asociada con el DRA posoperatoria en pacientes sometidos a cirug&#237;a coronaria&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">En nuestro estudio&#44; pretend&#237;amos determinar la asociaci&#243;n entre la hiperuricemia preoperatoria en pacientes de alto riesgo &#40;puntuaci&#243;n de Cleveland &#62;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>4&#41; sometidos a cirug&#237;a cardiaca&#44; y el riesgo de desarrollar DRA&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">M&#233;todos</span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Dise&#241;o del estudio</span><p id="par0040" class="elsevierStylePara elsevierViewall">Este estudio de cohortes prospectivo multic&#233;ntrico en 14 hospitales espa&#241;oles y brit&#225;nicos incluy&#243; a todos los pacientes consecutivos de 18 a&#241;os o m&#225;s con una puntuaci&#243;n Cleveland &#8805;<span class="elsevierStyleHsp" style=""></span>4 sometidos a cirug&#237;a cardiaca entre julio y diciembre de 2017 &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a>&#41;&#46; La puntuaci&#243;n de Cleveland es una escala bien validada para identificar a los pacientes con riesgo de DRA grave despu&#233;s de la cirug&#237;a cardiaca<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">11</span></a>&#46; Se incluyeron todos los procedimientos de cirug&#237;a cardiaca &#40;incluidos los casos de cirug&#237;a a&#243;rtica mayor que necesitaron circulaci&#243;n extracorp&#243;rea &#40;CEC&#41;&#44; excepto la pericardiectom&#237;a y el trasplante cardiaco&#46; Adem&#225;s&#44; se excluyeron los pacientes con insuficiencia renal grave preoperatoria &#40;definida como necesidad de di&#225;lisis o filtraci&#243;n glomerular estimada &#91;FGe&#93; &#60;<span class="elsevierStyleHsp" style=""></span>15<span class="elsevierStyleHsp" style=""></span>mL&#47;min&#47;1&#44;73 m<span class="elsevierStyleSup">2</span>&#41; o las embarazadas&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0045" class="elsevierStylePara elsevierViewall">Este estudio fue aprobado por los Comit&#233;s de &#201;tica de cada instituci&#243;n local y de conformidad con la declaraci&#243;n de Helsinki&#46; El consentimiento informado fue firmado por el paciente o su sustituto en la toma de decisiones durante el periodo perioperatorio&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Exposici&#243;n de inter&#233;s</span><p id="par0050" class="elsevierStylePara elsevierViewall">La cohorte se dividi&#243; en dos grupos&#44; los pacientes que ten&#237;an un AUS &#62;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>7<span class="elsevierStyleHsp" style=""></span>mg&#47;dL &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>190&#41; y aquellos que ten&#237;an un AUS &#60;<span class="elsevierStyleHsp" style=""></span>7<span class="elsevierStyleHsp" style=""></span>mg&#47;dL &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>71&#41; en el preoperatorio&#46; El AUS se midi&#243; en todos los pacientes&#44; el mismo d&#237;a&#44; antes de la cirug&#237;a&#46; Dado que el efecto oxidante del &#225;cido &#250;rico se manifiesta con un AUS &#62;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>5&#44;5<span class="elsevierStyleHsp" style=""></span>mg&#47;dL<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">12</span></a>&#44; se utiliz&#243; una variable categ&#243;rica&#44; y no continua&#46; El umbral de 7<span class="elsevierStyleHsp" style=""></span>mg&#47;dL o m&#225;s se utiliz&#243; bas&#225;ndose en estudios previos<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">12&#44;13</span></a>&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Variable dependiente primaria</span><p id="par0055" class="elsevierStylePara elsevierViewall">La variable dependiente primaria fue el DRA seg&#250;n la definici&#243;n de los criterios de AKIN &#40;estadios I&#44; II o III&#41;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">14</span></a>&#46; Para aplicar estos criterios&#44; se midi&#243; la creatinina a las seis&#44; 12&#44; 24 y 48 horas del posoperatorio&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">An&#225;lisis estad&#237;stico</span><p id="par0060" class="elsevierStylePara elsevierViewall">STATA Versi&#243;n 13&#46;0 &#40;Stata-Corp&#46; 2013&#46; Software estad&#237;stico Stata&#58; Release 13&#46; College Station&#44; TX&#58; Stata Corp LP&#41; se utiliz&#243; para todos los an&#225;lisis estad&#237;sticos&#46; Un valor p de 2 colas inferior a 0&#44;05 defini&#243; la significaci&#243;n estad&#237;stica&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Inicialmente&#44; se utilizaron estad&#237;sticas descriptivas para caracterizar a los pacientes dentro de estratos definidos por sus niveles preoperatorios de AUS &#40;es decir&#44; AUS &#62;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>7 vs&#46; AUS &#60;<span class="elsevierStyleHsp" style=""></span>7&#41;&#44; as&#237; como por su desarrollo de DRA posoperatorio &#40;DRA vs&#46; no DRA&#41;&#46; Las variables categ&#243;ricas se describieron mediante porcentajes&#44; y las variables continuas&#44; mediante medias con desviaciones est&#225;ndar o medianas con rangos intercuart&#237;licos&#46; Se utiliz&#243; la prueba de Shapiro-Wilk para determinar si las variables ten&#237;an una distribuci&#243;n normal&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">A continuaci&#243;n se utiliz&#243; un modelo de regresi&#243;n log&#237;stica multivariable para estimar la asociaci&#243;n ajustada entre la hiperuricemia y los resultados posoperatorios de inter&#233;s&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Las covariables incluidas fueron datos demogr&#225;ficos &#40;edad&#44; sexo&#41;&#44; area de superficie corporal&#44; reintervenci&#243;n&#44; FGe basal&#44; <span class="elsevierStyleItalic">New York Heart Association</span> &#91;NYHA&#93;&#41;&#44; comorbilidades &#40;diabetes mellitus&#44; enfermedad pulmonar obstructiva cr&#243;nica &#40;EPOC&#41;&#44; insuficiencia cardiaca congestiva &#40;ICC&#41;&#44; enfermedad renal cr&#243;nica &#91;ERC&#93;&#41;&#44; fracci&#243;n de eyecci&#243;n ventricular izquierda &#40;FEVI&#41;&#44; puntuaci&#243;n de Cleveland basal y tiempo de CEC&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Todos los resultados se expresaron como <span class="elsevierStyleItalic">Odds Ratio</span> &#40;OR&#41; ajustadas con intervalos de confianza &#40;IC&#41; 95&#37;&#46; Se evalu&#243; el rendimiento de estos modelos de regresi&#243;n mediante varios enfoques diferentes&#58; a&#41; evaluaci&#243;n de la discriminaci&#243;n del modelo mediante el estad&#237;stico c&#44; b&#41; validaci&#243;n &#171;<span class="elsevierStyleItalic">bootstrap</span>&#187; interna con 1&#46;000 r&#233;plicas&#44; c&#41; evaluaci&#243;n de cualquier multicolinealidad importante mediante el factor de inflaci&#243;n de la varianza&#44; y d&#41; un an&#225;lisis de sensibilidad en el que se repitieron los an&#225;lisis de regresi&#243;n excluyendo covariables que podr&#237;an estar en la v&#237;a causal entre hiperuricemia y DRA&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Tambi&#233;n se utilizaron m&#233;todos de emparejamiento por puntuje de propensi&#243;n &#40;70 pares emparejados&#41; para comparar los resultados de los pacientes con hiperuricemia frente a los que no la padec&#237;an&#46; La puntuaci&#243;n de propensi&#243;n se estim&#243; utilizando el paquete &#171;<span class="elsevierStyleItalic">pscore</span>&#187; de Stata&#44; que implementa un modelo de regresi&#243;n &#171;<span class="elsevierStyleItalic">probit</span>&#187; con la hiperuricemia como variable independiente&#46; Las variables predictoras cl&#237;nicamente importantes incluidas en el modelo <span class="elsevierStyleItalic">probit</span> fueron demogr&#225;ficas &#40;edad&#44; sexo&#41;&#44; area de superficie corporal&#44; reintervenci&#243;n&#44; FGe basal&#44; NYHA&#41;&#44; comorbilidades &#40;diabetes mellitus&#44; EPOC&#44; ICC&#44; ERC&#41;&#44; FEVI&#44; puntuaci&#243;n de Cleveland basal&#44; tiempo de CEC y tiempo de pinzamiento a&#243;rtico&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">Se realiz&#243; un emparejamiento 1&#58;1 con el vecino m&#225;s pr&#243;ximo utilizando el algoritmo &#171;<span class="elsevierStyleItalic">teffects psmatch</span>&#187; de Stata basado en la puntuaci&#243;n de propensi&#243;n estimada&#46; Se calcularon los efectos medios del tratamiento entre los individuos tratados utilizando el paquete &#171;<span class="elsevierStyleItalic">teffects</span>&#187; de Stata&#46; A continuaci&#243;n&#44; se expresaron los resultados como OR ajustadas con IC 95&#37;&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">El tama&#241;o de la muestra se determin&#243; por el n&#250;mero de pacientes elegibles que se sometieron a cirug&#237;a durante el periodo de tiempo de inter&#233;s&#46; Como se ha recomendado&#44; no se realiz&#243; un c&#225;lculo de potencia <span class="elsevierStyleItalic">post hoc</span>&#44; dado que ser&#237;a metodol&#243;gicamente inadecuado&#59; en su lugar&#44; se utilizaron los IC 95&#37; para ayudar a interpretar los resultados del an&#225;lisis<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">15</span></a>&#46;</p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Resultados</span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Datos descriptivos</span><p id="par0100" class="elsevierStylePara elsevierViewall">Nuestra cohorte incluy&#243; 261 pacientes consecutivos sometidos a cirug&#237;a cardiaca y con mayor riesgo de desarrollar DRA posoperatoria&#44; seg&#250;n una puntuaci&#243;n de Cleveland &#8805;<span class="elsevierStyleHsp" style=""></span>4&#46; Un total de 190 &#40;72&#44;8&#37;&#41; pacientes de nuestra cohorte eran hiperuric&#233;micos &#40;&#62;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>7<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#41; en el preoperatorio&#46; Se produjo DRA posoperatoria en 145 &#40;55&#44;5&#37;&#41; pacientes&#46; Entre los pacientes de toda la cohorte&#44; 41 &#40;15&#44;7&#37;&#41; fallecieron sin abandonar el hospital&#46; Los pacientes del grupo de hiperuricemia presentaban una mayor carga de comorbilidad &#40;p&#46; ej&#46;&#44; mayor peso&#44; menor FGe&#44; mayor creatinina preoperatoria y Hb A1C ligeramente superior &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">tabla 1</a>&#41;&#46; No se observaron diferencias entre ambos grupos en las caracteristicas intraoperatorias y complicaciones posoperatorias&#44; salvo un menor porcentaje de pacientes usaron dobutamina y un uso de mayor dosis de &#225;cido tranex&#225;mico en el grupo de hiperuricemia &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">tabla 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Resultados</span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Modelos de regresi&#243;n log&#237;stica univariable</span><p id="par0105" class="elsevierStylePara elsevierViewall">No se observaron diferencias estadisticamente significativas entre ambos grupos en cuanto a las probabilidades no ajustadas de DRA &#40;OR 1&#44;05&#59; IC 95&#37;&#58; 0&#44;6-1&#44;8&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;86&#41;&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">An&#225;lisis de emparejamiento por puntuaci&#243;n de propensi&#243;n</span><p id="par0110" class="elsevierStylePara elsevierViewall">Tras el emparejamiento por puntaje de propensi&#243;n&#44; las caracter&#237;sticas preoperatorias e intraoperatorias de los dos grupos fueron similares &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">tabla 3</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">Variable dependiente primaria&#58; DRA posoperatoria</span><p id="par0115" class="elsevierStylePara elsevierViewall">No hubo diferencias significativas entre los brazos con niveles elevados de AUS frente a los brazos con niveles normales de AUS con respecto a las probabilidades de DRA en el an&#225;lisis de pares emparejados por puntuaci&#243;n de propensi&#243;n &#40;OR 1&#44;05&#59; IC 95&#37;&#58; 0&#44;93-1&#44;19&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;37&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">tabla 4</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0160">Modelos de regresi&#243;n log&#237;stica multivariable</span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0165">Variable dependiente primaria&#58; DRA posoperatoria</span><p id="par0120" class="elsevierStylePara elsevierViewall">Tras el ajuste del riesgo basado en el modelo de regresi&#243;n log&#237;stica multivariable&#44; ser hiperuric&#233;mico &#40;&#62;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>7<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#41; en el preoperatorio no se asoci&#243; con un aumento significativo del riesgo de DRA &#40;OR ajustado 1&#44;58&#59; IC 95&#37;&#58; 0&#44;81-3&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;17&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">tabla 4</a>&#41; en nuestra cohorte de pacientes de alto riesgo&#46; El modelo de regresi&#243;n mostr&#243; un rendimiento estable en la validaci&#243;n interna &#171;<span class="elsevierStyleItalic">bootstrap</span>&#187;&#44; sin evidencia de multicolinealidad significativa y buena discriminaci&#243;n &#40;estad&#237;stico c 0&#44;74&#41;&#46; Como an&#225;lisis de sensibilidad&#44; se realiz&#243; un examen ajustado al riesgo mediante un modelo de regresi&#243;n log&#237;stica multivariable que inclu&#237;a las covariables&#44; uso de dobutamina intraoperatoria y dosis de &#225;cido tranex&#225;mico en el modelo&#44; y no se observaron diferencias en nuestro resultado primario&#44; DRA - OR 1&#44;72 &#40;IC 95&#37; 0&#44;84-3&#44;5&#41;&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;13 &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">tabla 4</a>&#41;&#46;</p></span></span></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0170">Discusi&#243;n</span><p id="par0125" class="elsevierStylePara elsevierViewall">Varios estudios epidemiol&#243;gicos han sugerido que la hiperuricemia se asocia con la hipertensi&#243;n&#44; las enfermedades cardiovasculares&#44; la diabetes mellitus y la progresi&#243;n de la ERC<a class="elsevierStyleCrossRefs" href="#bib0230"><span class="elsevierStyleSup">16&#8211;18</span></a>&#46; Adem&#225;s&#44; se ha observado que la hiperuricemia se asocia a DRA en diferentes escenarios cl&#237;nicos<a class="elsevierStyleCrossRefs" href="#bib0245"><span class="elsevierStyleSup">19&#44;20</span></a>&#46; En los &#250;ltimos a&#241;os se han realizado varios estudios para estimar si la hiperuricemia era factor de riesgo independiente para aumentar la tasa y&#47;o empeorar el pron&#243;stico de la DRA en la poblaci&#243;n general&#46; Uno de estos estudios es un metaan&#225;lisis realizado por Xu et al&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">12</span></a>&#44; en el que se observa una diferencia significativa en la tasa de DRA entre los pacientes con hiperuricemia y sin ella&#46; La causalidad entre hiperuricemia y DRA en la poblaci&#243;n general es objeto de debate&#46; Dos grandes ensayos cl&#237;nicos aleatorizados han demostrado recientemente que el tratamiento de la hiperuricemia con alopurinol no modifica la progresi&#243;n de la ERC en pacientes con enfermedad renal diab&#233;tica de temprana a moderada<a class="elsevierStyleCrossRefs" href="#bib0255"><span class="elsevierStyleSup">21&#44;22</span></a>&#46; Lo que sugiere que la hiperuricemia se asocia a un aumento de las comorbilidades&#44; pero no tiene una relaci&#243;n independiente con la progresi&#243;n de la ERC&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">Los pacientes sometidos a cirug&#237;a cardiaca presentan niveles elevados de &#225;cido &#250;rico debido a la coexistencia de ICC<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">23</span></a>&#44; ERC<a class="elsevierStyleCrossRefs" href="#bib0270"><span class="elsevierStyleSup">24&#44;25</span></a>&#44; lesi&#243;n por isquemia-reperfusi&#243;n y tratamiento diur&#233;tico&#46; Tras la cirug&#237;a cardiaca&#44; los niveles de &#225;cido &#250;rico pueden aumentar a&#250;n m&#225;s&#44; en el posoperatorio inmediato&#44; en respuesta a la isquemia tisular o a la lesi&#243;n renal<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">26</span></a>&#46; En este sentido&#44; el aumento del ASU podr&#237;a reflejar un estado de estr&#233;s oxidativo&#44; isquemia tisular o la presencia de vasoconstricci&#243;n renal<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">27</span></a>&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">Estos resultados concuerdan con otros estudios publicados que eval&#250;an el efecto de la hiperuricemia sobre la funci&#243;n renal en la poblaci&#243;n sometida a cirug&#237;a cardiaca<a class="elsevierStyleCrossRefs" href="#bib0200"><span class="elsevierStyleSup">10&#44;13&#44;28&#8211;30</span></a>&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">Los datos de un estudio de cohortes retrospectivo&#44; con 2&#46;185 pacientes<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">10</span></a>&#44; observaron que la hiperuricemia se asociaba a un aumento de la tasa del DRA&#46; Sin embargo&#44; esta cohorte inclu&#237;a una poblaci&#243;n de pacientes diferente&#44; con pacientes de m&#225;s bajo riesgo de desarrollar DRA&#46; Adem&#225;s&#44; en el modelo de regresi&#243;n log&#237;stica no se incluyeron variables cl&#237;nicas significativas importantes&#44; como la ICC&#44; la reintervenci&#243;n y la FEVI&#46; Adem&#225;s&#44; no se utiliz&#243; el an&#225;lisis de pares de emparejamiento por puntuaci&#243;n de propensi&#243;n para confirmar el an&#225;lisis de regresi&#243;n multivariable&#46; Adem&#225;s&#44; la capacidad de discriminaci&#243;n&#44; medida por los estad&#237;sticos c&#44; no mejor&#243; significativamente cuando se incluy&#243; el &#225;cido &#250;rico en el modelo multivariable&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">Ahsan-Ejaz et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">28</span></a> sugirieron que el &#225;cido &#250;rico podr&#237;a ser un nuevo factor de riesgo de DRA en pacientes sometidos a determinadas cirug&#237;as cardiacas&#44; como la reparaci&#243;n de aneurismas tor&#225;cicos y la cirug&#237;a valvular a&#243;rtica o mitral&#46; Sin embargo&#44; se trataba de un estudio de cohortes con una muestra peque&#241;a de 58 pacientes y con solo 18 casos de DRA&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">Otro estudio observacional retrospectivo con 190 pacientes observ&#243; que los niveles preoperatorios de AUS estaban relacionados con el DRA posoperatorio en una relaci&#243;n curva en forma de J<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">13</span></a>&#46; Sin embargo&#44; esta cohorte inclu&#237;a a pacientes de muy bajo riesgo&#44; y 87&#37; de los pacientes con DRA eran de grado AKIN I&#46; Adem&#225;s&#44; los resultados no se confirmaron mediante un an&#225;lisis de emparejamiento por puntuaci&#243;n de propensi&#243;n&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">Los datos de un reciente estudio retrospectivo observacional de gran tama&#241;o con 1&#46;420 pacientes mostraron que los pacientes con niveles m&#225;s altos de &#225;cido &#250;rico ten&#237;an una mayor incidencia de DRA<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">29</span></a>&#46; Sin embargo&#44; la cohorte inclu&#237;a una poblaci&#243;n de pacientes diferente con pacientes de m&#225;s bajo riesgo de desarrollar DRA&#46; Adem&#225;s&#44; en el modelo de regresi&#243;n log&#237;stica no se incluyeron variables cl&#237;nicas significativas importantes&#44; como la ICC&#44; la reintervenci&#243;n&#44; la FEVI y la arteriopat&#237;a perif&#233;rica&#46; Adem&#225;s&#44; la hiperuricemia no se asoci&#243; a DRA grave&#46; Adem&#225;s&#44; no se utiliz&#243; el an&#225;lisis de pares de emparejamiento por puntuaci&#243;n de propensi&#243;n para confirmar el an&#225;lisis de regresi&#243;n multivariable&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">Los datos de un estudio de cohortes retrospectivo con 1&#46;019 pacientes observaron que la hiperuricemia &#40;&#8805;<span class="elsevierStyleHsp" style=""></span>6&#44;5<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#41; estaba asociada a DRA<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">30</span></a>&#46; Sin embargo&#44; en el modelo de regresi&#243;n log&#237;stica no se incluyeron variables cl&#237;nicas significativas importantes&#44; como ICC&#44; reintervenci&#243;n&#44; diabetes mellitus&#44; tipo de cirug&#237;a&#44; cirug&#237;a de urgencia&#44; EPOC y arteriopat&#237;a perif&#233;rica&#46; Adem&#225;s&#44; la discriminaci&#243;n mediante estad&#237;sticos c no mejor&#243; significativamente cuando se incluy&#243; el &#225;cido &#250;rico en el modelo multivariable &#40;AUROC 0&#44;780 vs&#46; 0&#44;783 vs&#46; 0&#44;782&#41;&#46; Adem&#225;s&#44; no se utiliz&#243; el an&#225;lisis de pares de emparejamiento por puntuaci&#243;n de propensi&#243;n para confirmar el an&#225;lisis de regresi&#243;n multivariable&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">Al contrario de la mayor&#237;a de estos estudios mencionados&#44; en nuestro estudio de cohortes multic&#233;ntrico de 261 pacientes consecutivos con alto riesgo de desarrollar DRA-CS&#44; se observ&#243; que la hiperuricemia preoperatoria &#40;&#62;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>7<span class="elsevierStyleHsp" style=""></span>g&#47;dL&#41;&#44; en comparaci&#243;n con el &#225;cido &#250;rico &#60;<span class="elsevierStyleHsp" style=""></span>7<span class="elsevierStyleHsp" style=""></span>g&#47;dL&#44; no se asoci&#243; a riesgos significativamente mayores de DRA posoperatoria&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">Deben tenerse en cuenta algunas limitaciones de nuestro estudio&#46; En primer lugar&#44; hubo diferencias basales significativas entre los grupos con hiperuricemia y sin hiperuricemia&#46; Ajustamos estas diferencias para abordar esta cuesti&#243;n con dos m&#233;todos diferentes&#58; modelos de regresi&#243;n y an&#225;lisis de pares emparejados por puntuaci&#243;n de propensi&#243;n&#46; En segundo lugar&#44; no podemos excluir la posibilidad de confusi&#243;n residual no medida&#44; como ocurre con la mayor&#237;a de los estudios observacionales&#46; En tercer lugar&#44; los IC 95&#37; de nuestras estimaciones ajustadas fueron amplios&#46; As&#237; pues&#44; aunque la estimaci&#243;n puntual es tranquilizadora&#44; siguen siendo necesarios m&#225;s estudios para confirmar la repercusi&#243;n renal de la hiperuricemia en los pacientes de alto riesgo sometidos a cirug&#237;a&#46; En cuarto lugar&#44; la definici&#243;n AKIN de DRA utilizada en nuestra cohorte incluye un per&#237;odo de tiempo de 48<span class="elsevierStyleHsp" style=""></span>horas para los cambios agudos en la creatinina s&#233;rica&#44; que podr&#237;a ser demasiado corto&#44; en comparaci&#243;n con el per&#237;odo de tiempo de siete d&#237;as incluido en la definici&#243;n KDIGO&#46; Por &#250;ltimo&#44; en nuestra cohorte no se dispon&#237;a de la tasa de pacientes en tratamiento de la hiperuricemia&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">Los puntos fuertes de este estudio incluyen su poblaci&#243;n pragm&#225;tica de cirug&#237;a cardiaca de alto riesgo en el mundo real&#44; que incluye 14 hospitales&#44; y el ajuste del riesgo mediante diferentes m&#233;todos &#40;an&#225;lisis de pares emparejados por puntuaci&#243;n de propensi&#243;n y modelos de regresi&#243;n logistica multivariable&#41;&#46;</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0175">Conclusi&#243;n</span><p id="par0180" class="elsevierStylePara elsevierViewall">La hiperuricemia preoperatoria en pacientes de alto riesgo no se asoci&#243; a un mayor riesgo de DRA-CS en este estudio de cohortes prospectivo multic&#233;ntrico&#46;</p><p id="par0185" class="elsevierStylePara elsevierViewall">Todos los autores han participado en los siguientes aspectos&#58; 1&#41; la concepci&#243;n y el dise&#241;o del estudio&#44; o la adquisici&#243;n de datos&#44; o el an&#225;lisis y la interpretaci&#243;n de los datos&#44; 2&#41; la redacci&#243;n del art&#237;culo o su revisi&#243;n cr&#237;tica en busca de contenido intelectual importante&#44; 3&#41; la aprobaci&#243;n final de la versi&#243;n que se presentar&#225;&#44; y 4&#41; todos los autores aceptan ser responsables de todos los aspectos del trabajo para garantizar que las cuestiones relacionadas con la exactitud o la integridad de cualquier parte del trabajo se investiguen y resuelvan adecuadamente&#46;</p></span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0180">Declaraci&#243;n de autor&#237;a</span><p id="par0210" class="elsevierStylePara elsevierViewall">Todos los autores han participado en los siguientes aspectos&#58;</p><p id="par0215" class="elsevierStylePara elsevierViewall">1&#41; la concepci&#243;n y el dise&#241;o del estudio&#44; o la adquisici&#243;n de datos&#44; o el an&#225;lisis y la interpretaci&#243;n de los datos&#44; 2&#41; la redacci&#243;n del art&#237;culo o su revisi&#243;n cr&#237;tica en busca de contenido intelectual importante&#44; 3&#41; la aprobaci&#243;n final de la versi&#243;n que se presentar&#225;&#44; y 4&#41; todos los autores aceptan ser responsables de todos los aspectos del trabajo para garantizar que las cuestiones relacionadas con la exactitud o la integridad de cualquier parte del trabajo se investiguen yresuelvan adecuadamente&#46;</p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0185">Financiaci&#243;n</span><p id="par0190" class="elsevierStylePara elsevierViewall">Este estudio no cuenta con ninguna financiaci&#243;n ec&#243;nomica&#46;</p></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0190">Conflicto de intereses</span><p id="par0205" class="elsevierStylePara elsevierViewall">Los autrores declaran que no tienen ning&#250;n tipo de conflicto de intereses&#46;</p></span></span>"
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        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Objetivo</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">No est&#225; claro si la elevaci&#243;n de &#225;cido &#250;rico s&#233;rico &#40;AUS&#41; preoperatorio puede desempe&#241;ar un papel en el desarrollo de da&#241;o renal agudo &#40;DRA&#41; asociado a cirug&#237;a cardiaca &#40;DRA-CS&#41;&#46; Se realiz&#243; un estudio de cohortes para evaluar la influencia de la hiperuricemia en el DRA en pacientes de alto riesgo para desarrollar DRA-CS&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Dise&#241;o</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Estudio de cohortes prospectivo multic&#233;ntrico&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Entorno</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Catorce hospitales universitarios en Espa&#241;a y en Reino Unido&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Participantes</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Se estudiaron a 261 pacientes consecutivos con alto riesgo de desarrollar DRA-CS&#44; seg&#250;n una puntuaci&#243;n de Cleveland &#8805;<span class="elsevierStyleHsp" style=""></span>4 puntos&#44; de julio a diciembre de 2017&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Intervenciones</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Ninguna&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Mediciones y resultados principales</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Se utilizaron los criterios AKIN para la definici&#243;n de DRA&#46; Para determinar la asociaci&#243;n ajustada entre hiperuricemia &#40;&#62;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>7<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#41; e DRA se utilizaron modelos de regresi&#243;n log&#237;stica multivariable y an&#225;lisis de pares emparejados por puntuaje de propensi&#243;n&#46;</p><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">El AUS preoperatorio elevado &#40;&#62;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>7<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#41; estaba presente en 190 pacientes &#40;72&#44;8&#37;&#41;&#44; mientras que la DRA-CS se produjo en 145 pacientes &#40;55&#44;5&#37;&#41;&#46; En los modelos de regresi&#243;n log&#237;stica multivariable&#44; la hiperuricemia no se asoci&#243; con un aumento significativo del riesgo de DRA &#40;<span class="elsevierStyleItalic">Odds Ratio</span> &#91;OR&#93; ajustado&#58; 1&#44;58&#59; intervalo de confianza &#91;IC&#93; 95&#37;&#58; 0&#44;81-3&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;17&#41;&#46; En el an&#225;lisis de emparejamiento por puntaje de propensi&#243;n de 140 pacientes&#44; el grupo de hiperuricemia experiment&#243; probabilidades ajustadas similares de DRA &#40;OR 1&#44;05&#59; IC 95&#37;&#58; 0&#44;93-1&#44;19&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;37&#41;&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Conclusiones</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">La hiperuricemia no se asoci&#243; con un mayor riesgo de DRA en esta cohorte de pacientes con alto riesgo de desarrollar DRA-CS&#46;</p></span>"
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        "resumen" => "<span id="abst0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Purpose</span><p id="spar0095" class="elsevierStyleSimplePara elsevierViewall">It is unclear whether preoperative serum uric acid &#40;SUA&#41; elevation may play a role in the development of acute kidney injury &#40;AKI&#41; associated with cardiac surgery &#40;CSA-AKI&#41;&#46; We conducted a cohort study to evaluate the influence of preoperative hyperuricemia on AKI in patients at high risk for developing SC-AKI&#46;</p></span> <span id="abst0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Design</span><p id="spar0100" class="elsevierStyleSimplePara elsevierViewall">Multicenter prospective international cohort study&#46;</p></span> <span id="abst0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Setting</span><p id="spar0105" class="elsevierStyleSimplePara elsevierViewall">Fourteen university hospitals in Spain and the United Kingdom&#46;</p></span> <span id="abst0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Participants</span><p id="spar0110" class="elsevierStyleSimplePara elsevierViewall">We studied 261 consecutive patients at high risk of developing CSA-AKI&#44; according to a Cleveland score &#8805;4 points&#44; from July to December 2017&#46;</p></span> <span id="abst0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Interventions</span><p id="spar0115" class="elsevierStyleSimplePara elsevierViewall">None&#46;</p></span> <span id="abst0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Measurements and Main Results</span><p id="spar0120" class="elsevierStyleSimplePara elsevierViewall">AKIN criteria were used for the definition of AKI&#46; Multivariable logistic regression models and propensity score-matched pairwise analysis were used to determine the adjusted association between preoperative hyperuricemia &#40;&#62; &#61; 7 mg&#47;dL&#41; and AKI&#46; Elevated preoperative AUS &#40;&#62; &#61; 7 mg&#47;dL&#41; was present in 190 patients &#40;72&#46;8&#37;&#41;&#44; whereas CSA-AKI occurred in 145 patients &#40;55&#46;5&#37;&#41;&#46; In multivariable logistic regression models&#44; hyperuricemia was not associated with a significantly increased risk of AKI &#40;adjusted Odds Ratio &#91;OR&#93;&#58; 1&#46;58&#59; 95&#37; confidence interval &#91;CI&#93;&#58; 0&#46;81-3&#59; p &#61; 0&#46;17&#41;&#46; In propensity score-matched analysis of 140 patients&#44; the hyperuricemia group experienced similar adjusted odds of AKI &#40;OR 1&#46;05&#44; 95&#37; CI 0&#46;93-1&#46;19&#44; p &#61; 0&#46;37&#41;&#46;</p></span> <span id="abst0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Conclusions</span><p id="spar0125" class="elsevierStyleSimplePara elsevierViewall">Hyperuricemia was not associated with an increased risk of AKI in this cohort of patients undergoing cardiac surgery at high risk of developing CSA-AKI&#46;</p></span>"
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t">20 &#40;10&#44;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Clampaje a&#243;rtico&#44; media min&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">121&nbsp;\t\t\t\t\t\t\n
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ISSN: 00349356
Idioma original: Español
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