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      Association between severe chronic kidney disease defined by cystatin-c and creatinine and clinical outcomes in an elderly population - an observational study Translated title: Associação entre doença renal crônica grave definida por cistatina-c e creatinina e desfechos clínicos em uma população idosa - um estudo observacional

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          Estimated glomerular filtration rate (eGFR) based on serum cystatin-C (sCys) seems as accurate as when based on serum creatinine (sCr), but sCys seems a better predictor of adverse outcomes. We aimed to study whether sCys could be a reliable tool for the prediction of adverse outcomes in elderly patients with severe chronic kidney disease (CKD).


          A group of 348 elderly patients with non-end-stage CKD (stages 1-4, according to eGFR-EPI sCr and/or sCys), referred to our consultation unit during 2016, was retrospectively studied and divided into four exclusive categories: CKD_stage4_neither (eGFR-sCr≥30mL/min; eGFR-sCys≥30mL/min), CKD_stage4_sCr_only (eGFR-sCr<30mL/min), CKD_stage4_sCys_only (eGFR-sCys<30mL/min) and CKD_stage4_combined (eGFRsCr<30mL/min; eGFR-sCys<30mL/min). Baseline characteristics, predictors of death, and clinical events (cardiovascular events and admissions for cardiovascular, acute kidney injury or infectious events) were explored until December 2018.


          A 77±7.4 year-old cohort, with a modified Charlson Comorbidty Index (mCCI) of 3 (IQR:1-4), was followed-up during 29 (IQR: 26-33) months. There were no significant differences between the characteristics of the stage 4 groups. Survival analysis was stratified by follow-up at 12 months, and in the first year, survival curves of CKD_stage4_sCys_only and CKD_stage4_combined groups were significantly lower than the other groups (p=0.028). Adjusting for age, sex, and mCCI, CKD_stage4_sCys_only, conversely to CKD_stage4_sCr_only, had higher rates of clinical events (p<0.05) than CKD_stage4_neither group.


          In elderly patients with discordant CKD staging, sCys-based eGFR seems to be a better predictor of adverse outcomes than sCr-based eGFR. Patients with stage 4 CKD defined by sCr alone seem to behave similar to those with less severe CKD.



          A taxa estimada de filtração glomerular (TFGe) com base na cistatina-C sérica (Cis-C) parece ser tão precisa quanto aquela baseada na creatinina sérica (Cr), mas cis-C parece ser um melhor preditor de resultados adversos. Nosso objetivo foi avaliar se a cis-C poderia ser uma ferramenta confiável para a previsão de desfechos adversos em pacientes idosos com doença renal crônica grave (DRC).


          Um grupo de 348 pacientes idosos com DRC em estágio não terminal (estágios 1-4, de acordo com TFGe-EPI Cr e/ou Cis-C), encaminhados para nossa unidade de consulta durante 2016, foi estudado retrospectivamente e dividido em quatro categorias exclusivas: DRC_estágio 4 nenhum (TFGe-Cr≥30mL/min; TFGe -Cis-C≥30mL/min), DRC_estágio 4_Cr apenas (TFGe-Cr <30mL/min), DRC_estágio 4 _Cis-C_apenas (TFGe-Cis-C <30 mL/min), DRC_estágio4_combinado (TFGe-Cis-C <30mL/min. TFGe-Cr <30mL/min). Características basais, preditores de óbito e eventos clínicos (eventos cardiovasculares e internações por doenças cardiovasculares, lesão renal aguda ou eventos infecciosos) foram explorados até dezembro de 2018.


          Uma coorte de 77 ± 7,4 anos, com índice de comorbidade de Charlson modificado (mCCI) de 3 (IQR: 1-4), foi acompanhada durante 29 (IQR: 26-33) meses. Não houve diferenças significativas entre as características dos grupos no estágio 4. A análise de sobrevida foi estratificada pelo acompanhamento aos 12 meses, sendo que no primeiro ano, as curvas de sobrevida dos grupos DRC_estágio4_Cis-C_apenas e DRC_estágio4_ combinado foram significativamente inferiores quando comparadas com os restantes grupos (p = 0,028). Ajustando para idade, sexo e mCCI, DRC_estágio4_Cis-C_apenas, ao contrário do grupo DRC_estágio4_Cr_apenas, teve maiores taxas de eventos clínicos (p <0,05) do que o grupo DRC_estágio4_nenhum.


          Em pacientes idosos com estadiamento discordante da DRC, a TFGe baseada na Cis-C parece ser um melhor preditor de resultados adversos do que a TFGe baseada na Cr. Pacientes com DRC em estágio 4, definida apenas por Cr, parecem se comportar de forma semelhante àqueles com DRC menos grave.

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          Most cited references 30

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          Equations to estimate glomerular filtration rate (GFR) are routinely used to assess kidney function. Current equations have limited precision and systematically underestimate measured GFR at higher values. To develop a new estimating equation for GFR: the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Cross-sectional analysis with separate pooled data sets for equation development and validation and a representative sample of the U.S. population for prevalence estimates. Research studies and clinical populations ("studies") with measured GFR and NHANES (National Health and Nutrition Examination Survey), 1999 to 2006. 8254 participants in 10 studies (equation development data set) and 3896 participants in 16 studies (validation data set). Prevalence estimates were based on 16,032 participants in NHANES. GFR, measured as the clearance of exogenous filtration markers (iothalamate in the development data set; iothalamate and other markers in the validation data set), and linear regression to estimate the logarithm of measured GFR from standardized creatinine levels, sex, race, and age. In the validation data set, the CKD-EPI equation performed better than the Modification of Diet in Renal Disease Study equation, especially at higher GFR (P < 0.001 for all subsequent comparisons), with less bias (median difference between measured and estimated GFR, 2.5 vs. 5.5 mL/min per 1.73 m(2)), improved precision (interquartile range [IQR] of the differences, 16.6 vs. 18.3 mL/min per 1.73 m(2)), and greater accuracy (percentage of estimated GFR within 30% of measured GFR, 84.1% vs. 80.6%). In NHANES, the median estimated GFR was 94.5 mL/min per 1.73 m(2) (IQR, 79.7 to 108.1) vs. 85.0 (IQR, 72.9 to 98.5) mL/min per 1.73 m(2), and the prevalence of chronic kidney disease was 11.5% (95% CI, 10.6% to 12.4%) versus 13.1% (CI, 12.1% to 14.0%). The sample contained a limited number of elderly people and racial and ethnic minorities with measured GFR. The CKD-EPI creatinine equation is more accurate than the Modification of Diet in Renal Disease Study equation and could replace it for routine clinical use. National Institute of Diabetes and Digestive and Kidney Diseases.
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            The objective of this study was to develop a prospectively applicable method for classifying comorbid conditions which might alter the risk of mortality for use in longitudinal studies. A weighted index that takes into account the number and the seriousness of comorbid disease was developed in a cohort of 559 medical patients. The 1-yr mortality rates for the different scores were: "0", 12% (181); "1-2", 26% (225); "3-4", 52% (71); and "greater than or equal to 5", 85% (82). The index was tested for its ability to predict risk of death from comorbid disease in the second cohort of 685 patients during a 10-yr follow-up. The percent of patients who died of comorbid disease for the different scores were: "0", 8% (588); "1", 25% (54); "2", 48% (25); "greater than or equal to 3", 59% (18). With each increased level of the comorbidity index, there were stepwise increases in the cumulative mortality attributable to comorbid disease (log rank chi 2 = 165; p less than 0.0001). In this longer follow-up, age was also a predictor of mortality (p less than 0.001). The new index performed similarly to a previous system devised by Kaplan and Feinstein. The method of classifying comorbidity provides a simple, readily applicable and valid method of estimating risk of death from comorbid disease for use in longitudinal studies. Further work in larger populations is still required to refine the approach because the number of patients with any given condition in this study was relatively small.
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              Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization.

              End-stage renal disease substantially increases the risks of death, cardiovascular disease, and use of specialized health care, but the effects of less severe kidney dysfunction on these outcomes are less well defined. We estimated the longitudinal glomerular filtration rate (GFR) among 1,120,295 adults within a large, integrated system of health care delivery in whom serum creatinine had been measured between 1996 and 2000 and who had not undergone dialysis or kidney transplantation. We examined the multivariable association between the estimated GFR and the risks of death, cardiovascular events, and hospitalization. The median follow-up was 2.84 years, the mean age was 52 years, and 55 percent of the group were women. After adjustment, the risk of death increased as the GFR decreased below 60 ml per minute per 1.73 m2 of body-surface area: the adjusted hazard ratio for death was 1.2 with an estimated GFR of 45 to 59 ml per minute per 1.73 m2 (95 percent confidence interval, 1.1 to 1.2), 1.8 with an estimated GFR of 30 to 44 ml per minute per 1.73 m2 (95 percent confidence interval, 1.7 to 1.9), 3.2 with an estimated GFR of 15 to 29 ml per minute per 1.73 m2 (95 percent confidence interval, 3.1 to 3.4), and 5.9 with an estimated GFR of less than 15 ml per minute per 1.73 m2 (95 percent confidence interval, 5.4 to 6.5). The adjusted hazard ratio for cardiovascular events also increased inversely with the estimated GFR: 1.4 (95 percent confidence interval, 1.4 to 1.5), 2.0 (95 percent confidence interval, 1.9 to 2.1), 2.8 (95 percent confidence interval, 2.6 to 2.9), and 3.4 (95 percent confidence interval, 3.1 to 3.8), respectively. The adjusted risk of hospitalization with a reduced estimated GFR followed a similar pattern. An independent, graded association was observed between a reduced estimated GFR and the risk of death, cardiovascular events, and hospitalization in a large, community-based population. These findings highlight the clinical and public health importance of chronic renal insufficiency. Copyright 2004 Massachusetts Medical Society

                Author and article information

                J Bras Nefrol
                J Bras Nefrol
                Jornal Brasileiro de Nefrologia
                Sociedade Brasileira de Nefrologia
                30 November 2020
                Apr-Jun 2021
                : 43
                : 2
                : 165-172
                [1 ]Centro Hospitalar Universitário do Porto, Largo do Prof. Abel Salazar, Serviço de Nefrologia, Porto, Portugal.
                Author notes
                Correspondence to: Joana Tavares. E-mail: joanatavares91@ 123456gmail.com

                Authors’ Contribution

                All authors contributed to the study conception and design. Material preparation and data collection were performed by Joana Tavares, Josefina Santos, Filipa Silva, João Oliveira, Andreia Campos, and António Cabrita. Data analysis was performed by Jorge Malheiro. The first draft of the manuscript was written by Joana Tavares and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

                Conflict of Interest

                None declared.


                This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

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