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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Chronic kidney disease &#40;CKD&#41; is a public health problem with an estimated prevalence of around 10&#37; globally&#46; Due to the population ageing and increase in cardiovascular comorbidities it is expected for the prevalence of CKD to increase&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">1</span></a> In Portugal&#44; in 2018 a national survey has estimated CKD prevalence to be 20&#46;1&#37; in agreement with higher prevalence of CKD in Europe&#44; with a majority of patients in stage 3&#46;<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">2&#8211;4</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Patients with CKD are at increased risk of cardiovascular events and progression to end stage kidney disease &#40;ESKD&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">5</span></a> CKD stages are defined by eGFR and albuminuria&#44; which are traditionally used to estimate the risk of progression to ESKD&#46; Predicting the risk of progression to ESKD is challenging as the declining pattern of kidney function is variable between different renal diseases and individually within the same disease&#46; Therefore&#44; knowledge of risk predictors for the progression to ESKD is crucial in determining the appropriate treatment plan&#46;<a class="elsevierStyleCrossRefs" href="#bib0150"><span class="elsevierStyleSup">6&#44;7</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">In 2011&#44; Tangri et al&#46; developed the kidney failure risk equations &#40;KFRE&#41;&#44; a four-variable model to predict the two-year probability of requiring KRT&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">8</span></a> This is an internationally validated risk prediction which accurately predicts the risk of progression to ESKD&#46; The KFRE equation is calculated inputting routinely available variables such as age&#44; gender&#44; serum creatinine and albuminuria&#46; KFRE was initially developed in Canadian population&#44; but since then it has been extensively validated in multiple cohorts in non-North America setting&#46;<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">9&#8211;14</span></a> Other risk prediction scores have been published&#44; but they have not undergone such robust validation&#46;<a class="elsevierStyleCrossRefs" href="#bib0195"><span class="elsevierStyleSup">15&#44;16</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Since the accuracy of the prediction model might differ among different populations&#44; the aim of this study was to validate the KFRE in a Portuguese cohort&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Methods</span><p id="par0025" class="elsevierStylePara elsevierViewall">We performed a single center retrospective analysis of adult patients with CKD referred to a nephrology consult at the Division of Nephrology and Renal Transplantation of Centro Hospitalar Universit&#225;rio Lisboa Norte &#40;CHULN&#41; between January and June of 2018&#46; This study was approved by the Ethical Committee in agreement with institutional guidelines and informed consent was waived due to the retrospective and non-interventional nature of the study&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Adult patients with CKD stages 3&#8211;5 &#40;estimated GFR<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>60<span class="elsevierStyleHsp" style=""></span>ml&#47;min&#47;1&#46;73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>&#41; at the time of initial nephrology referral were included&#46; Exclusion criteria comprised &#40;a&#41; patients without two determinations of serum creatinine values more than 90 days apart&#44; &#40;b&#41; patients without a quantifiable proteinuria value at referral time&#44; &#40;c&#41; patients lost to follow-up&#46; Kidney transplant patients were not included in this study&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Patient variables were collected from individual clinical records&#46; The following variables were analyzed&#58; patient demographic characteristics &#40;age&#44; gender&#41;&#59; comorbidities &#40;diabetes mellitus&#44; hypertension&#44; cardiovascular disease &#91;ischemic cardiomyopathy&#44; heart failure&#93;&#41;&#59; laboratory values at referral &#40;serum creatinine&#44; albumin-to-creatinine ratio &#40;ACR&#41;&#41;&#46; CKD was defined and staged according to the KDIGO classification&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">17</span></a> Estimated GFR was calculated according to the CKD-EPI formula&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">18</span></a> Alternative measures of proteinuria &#40;urine protein-creatinine ratio and 24-h urine total protein&#41; were converted to ACR as is described in previous studies&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">14</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">The 4-variable KFRE &#40;age&#44; gender&#44; baseline eGFR and log urine ACR&#41; calibrated to a non-North American population was calculated&#44; as proposed by Tangri et al&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">14</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">The outcomes measured were kidney replacement therapy &#40;KRT&#41; requirement and mortality&#46; Follow-up was continued until 31st December 2020&#44; and data extraction occurred between January and March 2021&#46; Outcomes were ascertained by reviewing clinic records&#46;</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Statistical analysis</span><p id="par0050" class="elsevierStylePara elsevierViewall">Categorical variables were described as the total number and percentage for each category&#44; whereas continuous variables were described as the mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>standard deviation&#46; Continuous variables were assessed for normality of distribution with Kolmogorov&#8211;Smirnov test and compared with the Student&#39;s <span class="elsevierStyleItalic">t</span>-test or Mann&#8211;Whitney test accordingly&#46; Categorical variables were compared with the chi-square test&#46; One-way ANOVA was used for comparisons between groups&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Cox regression analysis was performed to evaluate the correlation between KFRE and KRT requirement&#46; The discriminatory ability for KFRE to predict KRT requirement in CKD patients was determined using the receiver operating characteristic &#40;ROC&#41; curve&#46; Using the Youden&#39;s index a cut-off value was defined as that with the highest validity&#46; Calibration was tested by the Hosmer&#8211;Lemeshow test&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">Data were expressed as hazards ratios &#40;HRs&#41; with 95&#37; confidence intervals &#40;CIs&#41;&#46; Statistical significance was defined as a <span class="elsevierStyleItalic">p</span>-value &#60;0&#46;05&#46; Statistical analysis was performed with the statistical software package SPSS for windows &#40;version 21&#46;0&#41;&#46;</p></span></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Results</span><p id="par0065" class="elsevierStylePara elsevierViewall">We focused on 360 patients after excluding 144 patients&#44; as depicted in <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall">In this cohort of patients referred to nephrology consult&#44; mean age was 74&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>12&#46;2 years and the majority were male &#40;54&#46;4&#37;&#41;&#46; Mean eGFR was 33&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>12&#46;13<span class="elsevierStyleHsp" style=""></span>ml&#47;min&#47;1&#46;73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>&#44; mean proteinuria was 571&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>848&#46;3<span class="elsevierStyleHsp" style=""></span>mg&#47;24<span class="elsevierStyleHsp" style=""></span>h&#46; Concerning comorbidities 90&#46;6&#37; of participants had hypertension&#44; 47&#46;8&#37; had cardiovascular disease and 45&#46;3&#37; had diabetes&#46; Baseline characteristics and outcomes are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0075" class="elsevierStylePara elsevierViewall">There were 213 &#40;59&#46;2&#37;&#41; patients classified as having CKD stage 3&#44; 132 &#40;36&#46;7&#37;&#41; as CKD stage 4 and only 15 &#40;4&#46;2&#37;&#41; as CKD stage 5&#46; Two hundred and forty six patients were at high risk of progression of CKD according to the KDIGO classification using GFR and albuminuria criteria&#44; as depicted in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0080" class="elsevierStylePara elsevierViewall">Twenty-three patients required KRT &#40;6&#46;4&#37;&#41; and 86 &#40;23&#46;9&#37;&#41; died in the two-year follow-up&#46; Need for KRT was significantly higher according to CKD stage &#91;G3 1&#46;4&#37; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>3&#41; vs&#46; G4 12&#46;1&#37; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>16&#41; vs&#46; G5 26&#46;7&#37; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>4&#41;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#93; as was mortality &#91;G3 16&#46;4&#37; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>35&#41; vs&#46; G4 33&#46;3&#37; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>44&#41; vs&#46; G5 46&#46;7&#37; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>7&#41;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#93;&#46; There was no correlation between KRT requirement and mortality &#40;23&#46;4 vs&#46; 30&#46;4&#37;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;447&#41;&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">The mean calculated risk score was 6&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>11&#46;2&#37;&#46; There was no statistical difference between CKD stages and KFRE score &#40;G3 5&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;0&#37; vs&#46; G4 6&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;4&#37; vs&#46; G5 5&#46;0<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;2&#37;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;611&#41;&#46; Baseline characteristics and outcomes according to KFRE score outlined in <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0090" class="elsevierStylePara elsevierViewall">The KFRE accurately predicted the two-year risk of progression to KRT&#44; with an hazard ratio of 1&#46;1 &#91;95&#37; CI &#40;1&#46;06&#8211;1&#46;12&#41;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#93;&#46; The Hosmer&#8211;Lemeshow test indicated good fit of this model &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;081&#41;&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">The KFRE predicted progression to requirement of KRT with an auROC of 0&#46;903&#44; &#91;95&#37; CI &#40;0&#46;86&#8211;0&#46;95&#41;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#93; &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#44; with a sensitivity 91&#46;3&#37; and specificity of 71&#46;8&#37; &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#41;&#46; The optimal KFRE cut-off was &#62;4&#46;5&#37;&#44; with an hazard ratio of 26&#46;7 &#91;95&#37; CI &#40;6&#46;15&#8211;116&#46;3&#41;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#93; for 2-year risk of KRT&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><p id="par0100" class="elsevierStylePara elsevierViewall">One hundred and sixteen &#40;32&#46;2&#37;&#41; patients had KFRE<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>4&#46;5&#37; the majority &#40;61&#46;2&#37;&#41; being males with mean age of 74&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>12&#46;3 years&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">These patients had significantly lower baseline eGFR &#40;22&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&#46;9 vs&#46; 38&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>10&#46;8<span class="elsevierStyleHsp" style=""></span>ml&#47;min&#47;1&#46;73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#44; higher albuminuria &#40;1331&#46;79<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1146&#46;43 vs&#46; 209&#46;52<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>454&#46;2<span class="elsevierStyleHsp" style=""></span>mg&#47;24<span class="elsevierStyleHsp" style=""></span>h&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; and higher serum creatinine &#40;2&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;84 vs&#46; 1&#46;68<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;65<span class="elsevierStyleHsp" style=""></span>mg&#47;dl&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">Additionally&#44; this group required more KRT &#40;18&#46;1 vs&#46; 0&#46;82&#37;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; and mortality was also higher in these patients &#40;41&#46;4 vs&#46; 15&#46;6&#37;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Mortality was higher in patients older than 70 years &#40;89&#46;5 vs&#46; 55&#46;6&#37;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#44; patients with hypertension &#40;95&#46;4 vs&#46; 87&#46;7&#37;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;038&#41;&#44; cardiovascular disease &#40;65&#46;5 vs&#46; 38&#46;5&#37;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; and patients with KFRE<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>4&#46;5&#37; &#40;52&#46;6 vs&#46; 18&#46;0&#37;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46; On a multivariate analysis including hypertension&#44; cardiovascular disease and KFRE<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>4&#46;5&#37;&#44; cardiovascular disease &#91;OR 2&#46;97&#44; 95&#37; CI &#40;1&#46;76&#8211;5&#46;00&#41;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#93; and KFRE<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>4&#46;5&#37; &#91;OR 4&#46;48&#44; 95&#37; CI &#40;2&#46;67&#8211;7&#46;49&#41;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#93; were significant predictors of mortality&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Discussion</span><p id="par0120" class="elsevierStylePara elsevierViewall">In this cohort of 360 patients referred to nephrology consult 6&#46;4&#37; required KRT and 23&#46;9&#37; died in the two-year follow-up&#46; The KFRE accurately predicted the two-year risk of progression to KRT&#44; with a good performance &#91;AUC 0&#46;903 &#40;0&#46;86&#8211;0&#46;95&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#93; and a 91&#46;3&#37; sensitivity and 71&#46;8&#37; specificity&#46; This is in line with the performance of KFRE in other populations&#44; meaning that the use of this risk score in the Portuguese population is as adequate&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">14</span></a> Additionally&#44; we identified that KFRE<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>4&#46;5&#37; was a significant risk predictor of mortality on a two-year follow-up&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">The original KFRE development cohort included 3449 Canadian patients with CKD stages 3&#8211;5 of whom 11&#37; &#40;386&#41; progressed to ESKD in the 2-year follow-up&#46; Tangri et al&#46; developed several predictive models for the risk of progression of CKD&#46; The model including only age and gender performed poorly but the addition of baseline eGFR and uACR improved the predictive model significantly&#46; The improvement in discrimination between these models highlights the importance of eGFR and albuminuria for predicting progression of CKD&#46; Indeed&#44; the 4-variable model including age&#44; gender&#44; baseline eGFR and uACR had a good discrimination &#40;C-statistic of 0&#46;910&#59; 95&#37; CI&#44; 0&#46;894&#8211;0&#46;926&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#44; which maintained good discrimination in the validation cohort &#40;C-statistic 0&#46;83&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">8</span></a> This is an easily calculated score which incorporates demographic and laboratory data which is routinely obtained in CKD patients&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">Further studies identified differences in the estimated risk between regions which required usage of calibration factor to account for the increased baseline risk in North America populations&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">14</span></a></p><p id="par0135" class="elsevierStylePara elsevierViewall">Wang et al&#46; used the recalibrated KFRE in a cohort of 17&#44;271 participants from Southeast Asia with ESKD incidence of 2&#46;8&#37; and achieved good discrimination &#40;auROC 0&#46;96&#44; 95&#37; CI 0&#46;95&#8211;0&#46;97&#41;&#46; The recalibration model accounted for baseline risk differences between populations and at a 2-year follow-up&#44; a threshold risk of &#62;9&#37; presented a sensitivity of 93&#37; and specificity of 86&#37; for ESKD&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">19</span></a> The recalibrated KFRE was also studied in a cohort of 35&#44;539 patients referred from primary care in the United Kingdom&#44; of whom only 1&#46;21&#37; progressed to ESKD at a 5-year follow-up&#46; The use of KFRE in this population also revealed good discrimination of the prediction model &#40;C-statistics 0&#46;926&#41;&#44; and a KFRE threshold of &#8805;5&#37; they achieved a sensitivity of 6&#46;8&#37; and specificity of 99&#46;7&#37;&#46; The low sensitivity might be explained by the low incidence of ESKD in the cohort&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">20</span></a> In a cohort of 595 Dutch CKD patients with mean eGFR 33&#46;3<span class="elsevierStyleHsp" style=""></span>ml&#47;min&#47;1&#46;73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span> and an incidence of ESKD of 19&#37;&#44; Peters et al&#46; demonstrated that the 4-variable KFRE performed similarly with good discrimination &#40;auROC 0&#46;88&#44; 95&#37; CI 0&#46;85&#8211;0&#46;91&#41;&#46; Defining a threshold of lower risk of ESKD with KFRE<span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>20&#37; achieve a sensitivity of 89&#37; and specificity of 69&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">21</span></a> This was an important study as it validated the KFRE in an European cohort&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">In our study&#44; the recalibrated KFRE performed similarly with an auROC of 0&#46;903&#44; a sensitivity 91&#46;3&#37; and specificity of 71&#46;8&#37;&#44; which means that this score accurately predicts the risk of CKD progression in the Portuguese population&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">The KFRE is a simple and easily calculated risk score which relies on routinely collected laboratory data&#44; and could be integrated into electronic medical records and information systems&#46; The widespread use of this risk score in clinical practice can lead to the improvement in the management of CKD patients&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">6</span></a> Firstly this could be used in determining nephrology referral as patients at high risk benefit from strategies to delay CKD progression&#46; As such&#44; the existence of a tangible score can improve the risk communication and better educate patients of their disease and prognosis&#44; as it has been shown that up to 40&#37; of CKD patients have a misperception of the risk of progression of their disease&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">22</span></a> Thus&#44; based on the risk of CKD progression&#44; the timing of modality education may also be determined and timely vascular access creation addressed&#46; In low-risk patients&#44; modality education and planning might create unnecessary anxiety resulting in outdated or irrelevant treatment plans as these low risk patients also tend to have higher risk of mortality than ESKD&#46; As for dialysis access creation&#44; the routine use of the KFRE might minimize starting dialysis with a catheter while avoiding access creation in patient who might die before ESKD&#46; Tangri et al&#46; suggests vascular access planning in patients with a eGFR<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>20<span class="elsevierStyleHsp" style=""></span>ml&#47;min&#47;1&#46;73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span> and a two year KFRE<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>40&#37; although this has not been prospectively evaluated&#46; Therefore&#44; not only can the KFRE be used to improve patient management and communication&#44; it might also enhance the allocation of appropriate resources and deliver cost-effective care to CKD patients&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">Interestingly&#44; Kwek et al&#46; studied 1&#46;128 CKD patients from Singapore in whom the KFRE had a good predictive ability and categorized patients into low &#40;&#60;5&#37;&#41;&#44; medium &#40;5&#8211;14&#46;99&#37;&#41; and high risk &#40;&#8805;15&#37;&#41;&#44; which might aid in management of patients with CKD stage 3 and 4&#46; They proposed that patients with low risk could be managed in primary care and high risk patients should be referred to a nephrologist&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">23</span></a> The triage of nephrologist referral based on the KFRE was also studied recently&#46; In their study&#44; a risk lower than 3&#37; at five years was used as threshold and these CKD patients were returned to primary care&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">24</span></a> In our cohort a cut-off at 4&#46;5&#37; had the best performance&#44; as these patients had significantly more KRT events &#40;HR 26&#46;7 &#91;95&#37; CI 6&#46;15&#8211;116&#46;3&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#93;&#41; on a 2-year follow-up&#46; This clearly establishes a threshold for nephrologists to be aware of when caring for CKD patients as these should be referred for KRT planning and vascular access creation&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">In our cohort there was a 24&#37; mortality on the two-year follow-up&#46; This might explain the low percentage of patients which required KRT over this time period &#40;6&#46;4&#37;&#41; as a higher KFRE was also associated with a higher mortality risk&#46; Indeed&#44; mortality was higher in older patients&#44; with more advanced CKD and more cardiovascular disease&#46; As we did not assess causes of mortality&#44; we can assume cardiovascular death was it is one of the most frequent causes of mortality in CKD patients&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">5</span></a> Nevertheless&#44; we might presume this significant mortality rate may be a consequence of the COVID-19 pandemic in a fragile population&#46; We highlight the importance of the KFRE to identify patients at-risk&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">This study has certain limitations which must be addressed&#46; Firstly&#44; the relatively small size of our cohort&#44; the single-center and the retrospective nature of our study limit its generalizability&#46; Secondly&#44; we did not assess for the CKD causes&#46; Thirdly&#44; we did not determine if KRT requirement was promoted by an acute event&#46; We assume a possible risk of selection bias due to referral of patients who empirically appeared to have greater risk of kidney disease&#46; Fourthly&#44; we did not assess if patients were selected for palliative care&#46; And finally&#44; we did not assess the causes of mortality in these patients&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">Our study has some important noteworthy virtues&#46; This is the first study to validate the risk score of CKD progression in a Portuguese population&#46; Secondly&#44; we included a recent cohort of patients&#44; meaning that the KFRE is still reliable and up-to-date&#46; Despite the retrospective design&#44; the studied variables were routinely recorded in daily practice which allowed for the analysis of important covariates with impact on CKD progression&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">In conclusion&#44; we have independently validated the 2-year KFRE and shown that it has excellent discrimination in a Portuguese cohort&#46; The KFRE should be incorporated in clinical care of patients with CKD to improve patient-clinician dialogue and provide guidance on timing of referral for nephrology evaluation and planning for dialysis access&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Ethics approval and consent to participate</span><p id="par0175" class="elsevierStylePara elsevierViewall">The study was approved by the Ethical Committee at the Centro Hospitalar Universit&#225;rio Lisboa Norte&#44; EPE&#44; in agreement with institutional guidelines&#46; Informed consent was waived by the Ethical Committee due to the retrospective and non-interventional nature of the study&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Consent for publication</span><p id="par0180" class="elsevierStylePara elsevierViewall">The authors give their consent for publication&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Availability of data and material</span><p id="par0185" class="elsevierStylePara elsevierViewall">Not applicable&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Authors&#8217; contributions</span><p id="par0190" class="elsevierStylePara elsevierViewall">The authors participated as follows&#58; BMS drafted the article&#44; JC participated in the collection of data&#46; CO and JG made substantial contributions to the study concept and design&#44; analysis and interpretation of data&#44; and were involved in revising it critically for important intellectual content&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Funding</span><p id="par0195" class="elsevierStylePara elsevierViewall">There was no funding for this study&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Conflict of interests</span><p id="par0200" class="elsevierStylePara elsevierViewall">There is no conflict of interest&#46;</p></span></span>"
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    "fechaRecibido" => "2021-09-16"
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            0 => "Chronic kidney disease"
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            2 => "Kidney replacement therapy"
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            0 => "Enfermedad renal cr&#243;nica"
            1 => "Ecuaci&#243;n de riesgo de insuficiencia renal"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">In chronic kidney disease &#40;CKD&#41; patients&#44; the risk of kidney replacement therapy &#40;KRT&#41; is highly variable&#46; In 2011&#44; Tangri et al&#46; developed the kidney failure risk equations &#40;KFRE&#41; to predict the 2 and 5-year probability of requiring kidney replacement therapy &#40;KRT&#41;&#46; The KFRE is an easily calculated 4-variable equation which has been extensively validated in multiple cohorts&#46; The aim of this study was to validate this risk score in a Portuguese cohort&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">We conducted a retrospective analysis of CKD patients stage 3&#8211;5 referred for nephrology consult at Centro Hospitalar Universit&#225;rio Lisboa Norte during the first 6 months of 2018&#46; Age&#44; gender&#44; estimated glomerular filtration rate &#40;eGFR&#41; and albuminuria were assessed&#46; The 4-variable kidney failure risk equation &#40;KFRE&#41; calibrated to a non-North American population was calculated&#46; Requirement of KRT was assessed in a 2-year follow-up&#46; We assessed the Cox logistic regression method of the KFRE to predict KRT requirement and the discriminatory ability was determined using the receiver operating characteristic &#40;ROC&#41; curve&#46; A cut-off value was defined as that with the highest validity&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">360 patients were included and 54&#46;4&#37; were male&#46; Mean age was 74&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>12&#46;2 years&#44; serum creatinine was 1&#46;97<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;84<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#44; eGFR was 33&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>12&#46;13<span class="elsevierStyleHsp" style=""></span>ml&#47;min&#47;1&#46;73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span> and albuminuria was 571&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>848&#46;3<span class="elsevierStyleHsp" style=""></span>mg&#47;g&#46; Mean calculated risk score was 6&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>11&#46;2&#37;&#46; Twenty-three patients required KRT &#40;6&#46;4&#37;&#41; in the two-year follow-up&#46; The hazard ratio was 1&#46;1 &#91;95&#37; CI &#40;1&#46;06&#8211;1&#46;12&#41;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#93; for the 2-year risk of KRT&#46; The KFRE predicted progression to KRT requirement with an auROC of 0&#46;903&#44; &#91;95&#37; CI &#40;0&#46;86&#8211;0&#46;95&#41;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#93;&#44; with a sensitivity 91&#46;3&#37; and specificity of 71&#46;8&#37;&#46; The optimal KFRE cut-off was &#62;4&#46;5&#37; for 2-year nephrologist referral&#44; with an hazard ratio of HR 26&#46;7 &#91;95&#37; CI &#40;6&#46;15&#8211;116&#46;3&#41;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#93; for 2-year risk of KRT requirement&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Discussion</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">We have independently externally validated the 2-year KFRE and shown that it has excellent discrimination&#46; The KFRE should be incorporated in clinical care of patients with CKD to improve patient-clinician dialogue and provide guidance on timing of referral for nephrology evaluation and planning for dialysis access&#46;</p></span>"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introducci&#243;n</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">En pacientes con enfermedad renal cr&#243;nica &#40;ERC&#41;&#44; el riesgo de la terapia de reemplazo renal &#40;TRR&#41; es muy variable&#46; En 2011&#44; Tangri et al&#46; desarrollaron las ecuaciones de riesgo de insuficiencia renal &#40;KFRE&#41; para predecir la probabilidad de 2 y 5<span class="elsevierStyleHsp" style=""></span>a&#241;os de requerir terapia de reemplazo renal &#40;KRT&#41;&#46; El KFRE es una ecuaci&#243;n de 4 variables de f&#225;cil c&#225;lculo que ha sido ampliamente validada en m&#250;ltiples cohortes&#46; El objetivo de este estudio fue validar esta puntuaci&#243;n de riesgo en una cohorte portuguesa&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Se realiz&#243; un an&#225;lisis retrospectivo de pacientes con ERC estadio 3-5 remitidos para consulta de Nefrolog&#237;a en el Centro Hospitalario Universit&#225;rio Lisboa Norte durante los primeros 6<span class="elsevierStyleHsp" style=""></span>meses de 2018&#46; Se evaluaron la edad&#44; el sexo&#44; el filtrado glomerular estimado &#40;TFGe&#41; y la albuminuria&#46; Se calcul&#243; la ecuaci&#243;n de riesgo de insuficiencia renal &#40;KFRE&#41; de 4 variables calibrada para una poblaci&#243;n no norteamericana&#46; La necesidad de KRT se evalu&#243; en un seguimiento de 2<span class="elsevierStyleHsp" style=""></span>a&#241;os&#46; Evaluamos el m&#233;todo de regresi&#243;n log&#237;stica de Cox del KFRE para predecir el requisito de KRT&#44; y la capacidad discriminatoria se determin&#243; utilizando la curva de caracter&#237;stica operativa del receptor &#40;ROC&#41;&#46; Se defini&#243; como valor de corte el de mayor validez&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Se incluyeron 360 pacientes&#44; y el 54&#44;4&#37; eran varones&#46; La edad media fue de 74&#44;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>12&#44;2 a&#241;os&#44; la creatinina s&#233;rica de 1&#44;97<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#44;84<span class="elsevierStyleHsp" style=""></span>mg&#47;dl&#44; la TFGe de 33&#44;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>12&#44;13<span class="elsevierStyleHsp" style=""></span>ml&#47;min&#47;1&#44;73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span> y la albuminuria de 571&#44;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>848&#44;3<span class="elsevierStyleHsp" style=""></span>mg&#47;g&#46; La puntuaci&#243;n de riesgo media calculada fue de 6&#44;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>11&#44;2&#37;&#46; Veintitr&#233;s pacientes requirieron KRT &#40;6&#44;4&#37;&#41; en los 2<span class="elsevierStyleHsp" style=""></span>a&#241;os de seguimiento&#46; El cociente de riesgos instant&#225;neos fue de 1&#44;1 &#40;IC del 95&#37;&#58; 1&#44;06-1&#44;12&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41; para el riesgo de 2<span class="elsevierStyleHsp" style=""></span>a&#241;os de KRT&#46; El KFRE predijo la progresi&#243;n al requerimiento de KRT con un auROC de 0&#44;903 &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#59; IC del 95&#37;&#58; 0&#44;86-0&#44;95&#41;&#44; con una sensibilidad del 91&#44;3&#37; y una especificidad del 71&#44;8&#37;&#46; El punto de corte &#243;ptimo de KFRE fue &#62;<span class="elsevierStyleHsp" style=""></span>4&#44;5&#37; para la derivaci&#243;n al nefr&#243;logo de 2<span class="elsevierStyleHsp" style=""></span>a&#241;os&#44; con un &#237;ndice de riesgo de HR 26&#44;7 &#40;IC del 95&#37;&#58; 6&#44;15-116&#44;3&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41; para el riesgo de 2<span class="elsevierStyleHsp" style=""></span>a&#241;os de necesidad de KRT&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Discusi&#243;n</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Hemos validado externamente de forma independiente el KFRE de 2<span class="elsevierStyleHsp" style=""></span>a&#241;os y hemos demostrado que tiene una discriminaci&#243;n excelente&#46; El KFRE debe incorporarse en la atenci&#243;n cl&#237;nica de los pacientes con ERC para mejorar el di&#225;logo entre el m&#233;dico y el paciente y proporcionar orientaci&#243;n sobre el momento de la derivaci&#243;n para la evaluaci&#243;n nefrol&#243;gica y la planificaci&#243;n del acceso a di&#225;lisis&#46;</p></span>"
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Cardiovascular disease</span>&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\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t  " align="left" valign="\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="elsevierStyleItalic">KFRE score</span>&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">6&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>11&#46;2&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
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">KFRE score &#8805;4&#46;5&#37; &#8211; n &#40;&#37;&#41;</span>&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">116 &#40;32&#46;2&#41;&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"><span class="elsevierStyleItalic">KFRE score &#60;3&#37; &#8211; n &#40;&#37;&#41;</span>&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">218 &#40;60&#46;6&#41;&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"><span class="elsevierStyleItalic">KFRE score 3 to &#60;5&#37; &#8211; n &#40;&#37;&#41;</span>&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
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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"><span class="elsevierStyleItalic">KFRE score 5 to &#60;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">25&#37; &#8211; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \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">84 &#40;23&#46;3&#41;&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"><span class="elsevierStyleItalic">KFRE score 25 to &#60;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">50&#37; &#8211; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \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">16 &#40;4&#46;4&#41;&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"><span class="elsevierStyleItalic">KFRE score &#8805;50&#37; &#8211; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \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">5 &#40;1&#46;4&#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  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Outcomes</span></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"><span class="elsevierStyleHsp" style=""></span>eGFR &#60;15<span class="elsevierStyleHsp" style=""></span>ml&#47;min&#47;1&#46;73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\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>KRT &#8211; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#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\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Mortality &#8211; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">38&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">35&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">39&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">58&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">132&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">G5&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&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">11&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="char" valign="\n
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                  \t\t\t\t">15&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">Total&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">129&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">101&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">130&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">360&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Characteristic&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t\ttop\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\ttop\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;593&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
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\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
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                  \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">2&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;84&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\ttop\n
                  \t\t\t\t">1&#46;68<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;65&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="char" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
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                  \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">38&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>10&#46;8&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="char" valign="\n
                  \t\t\t\t\ttop\n
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                  \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
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
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                  \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"><span class="elsevierStyleItalic">CKD Stage 3</span>&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">21 &#40;18&#46;1&#41;&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">192 &#40;78&#46;7&#41;&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="char" valign="\n
                  \t\t\t\t\ttop\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"><span class="elsevierStyleItalic">CKD Stage 4</span>&nbsp;\t\t\t\t\t\t\n
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                  \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">80 &#40;69&#46;0&#41;&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">52 &#40;21&#46;3&#41;&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\ttop\n
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                  \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
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t">0 &#40;0&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\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
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                  \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">53 &#40;45&#46;7&#41;&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">119 &#40;48&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;936&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
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">102 &#40;87&#46;9&#41;&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\ttop\n
                  \t\t\t\t">224 &#40;91&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">0&#46;794&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
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                  \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">51 &#40;44&#46;0&#41;&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">112 &#40;45&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">0&#46;950&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\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"><span class="elsevierStyleHsp" style=""></span>eGFR<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>15<span class="elsevierStyleHsp" style=""></span>ml&#47;min&#47;1&#46;73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>&nbsp;\t\t\t\t\t\t\n
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                  \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">29 &#40;25&#46;0&#41;&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">7 &#40;2&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \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"><span class="elsevierStyleHsp" style=""></span>KRT &#8211; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \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">21 &#40;18&#46;1&#41;&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">2 &#40;0&#46;82&#41;&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="char" valign="\n
                  \t\t\t\t\ttop\n
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                  \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"><span class="elsevierStyleHsp" style=""></span>Mortality &#8211; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&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">48 &#40;41&#46;4&#41;&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">38 &#40;15&#46;6&#41;&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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