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      Does Cystatin C have a role as metabolic surrogate in peritoneal dialysis beyond its association with residual renal function? Translated title: Teria a Cistatina C um papel como substituto metabólico na diálise peritoneal além de sua associação com a função renal residual?

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          ABSTRACT

          Introduction:

          It has been suggested that cystatin C levels are modified by obesity and inflammation. Furthermore, cystatin C has been associated with cardiovascular events and mortality outcomes.

          Aim:

          To study the association of cystatin C with the metabolic profile and cardiovascular disease of peritoneal dialysis patients.

          Methods:

          Data collected included clinical, laboratorial, and multifrequency bioimpedance assessment of 52 stable peritoneal dialysis patients. Minimal residual renal function was defined as > 2mL/min/1.73m 2.

          Results:

          Serum cystatin C was not significantly associated with peritoneal or urinary cystatin C excretion. Negative correlation of cystatin C with normalized protein catabolic rate (rho -0.33, p = 0.02) and a trend towards positive correlation with relative body fat (rho 0.27, p = 0.05) were not independent from residual renal function. Cystatin C was not significantly associated with cardiovascular disease ( p = 0.28), nor with glycated hemoglobin ( p = 0.19) or c-reactive protein ( p = 0.56). In the multivariate model, both age and diabetes were the strongest predictors of cardiovascular disease (odds ratio 1.09, p = 0.029 and odds ratio 29.95, p = 0.016, respectively), while relative body fat was negatively associated with cardiovascular disease ( p = 0.038); neither cystatin C ( p = 0.096) nor minimal residual renal function ( p = 0.756) reached a significant association with cardiovascular disease.

          Conclusions:

          In this group of peritoneal dialysis patients, cystatin C did not correlate with the metabolic or inflammatory status, nor cardiovascular disease, after adjustment for residual renal function.

          RESUMO

          Introdução:

          Tem sido sugerido que os níveis de cistatina C são modificados pela obesidade e inflamação. Além disso, a cistatina C tem sido associada a eventos cardiovasculares e desfechos de mortalidade.

          Objetivo:

          Estudar a associação da cistatina C com o perfil metabólico e doença cardiovascular de pacientes em diálise peritoneal.

          Métodos:

          Os dados coletados incluíram avaliação clínica, laboratorial e de bioimpedância múltipla de 52 pacientes estáveis em diálise peritoneal. A função renal residual mínima foi definida como > 2mL/min/1,73m 2.

          Resultados:

          A cistatina C sérica não esteve significativamente associada à excreção peritoneal ou urinária. A correlação negativa da cistatina C com a taxa catabólica protéica normalizada (rho -0,33, p = 0,02) e uma tendência de correlação positiva com a gordura corporal relativa (rho 0,27, p = 0,05) não foram independentes da função renal residual. A cistatina C não se associou significativamente à doença cardiovascular ( p = 0,28), nem com hemoglobina glicada ( p = 0,19) ou proteína C reativa ( p = 0,56). No modelo multivariado, idade e diabetes foram os mais fortes preditores de doença cardiovascular (razões de probabilidade 1,09, p = 0,029 e 29,95, p = 0,016, respectivamente) enquanto a gordura corporal relativa se associou negativamente à doença cardiovascular ( p = 0,038). A cistatina C não se associou significativamente com doença cardiovascular ( p = 0,096), tampouco a função residual mínima ( p = 0,756).

          Conclusão:

          Neste grupo de pacientes em diálise peritoneal, a cistatina C não se correlacionou com o estado metabólico ou inflamatório, nem com doença cardiovascular, após ajuste para função renal residual.

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          Most cited references23

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          Cystatin C: an improved estimator of glomerular filtration rate?

          Glomerular filtration rate (GFR) is routinely assessed by measuring the concentrations of endogenous serum markers such as blood urea nitrogen and serum creatinine (SCr). Although widely used, these endogenous markers are not ideal and do not perform optimally in certain clinical settings. The purpose of this review is to critically review the potential utility of cystatin C (CysC), especially in patient populations in which CysC may have an advantage over routinely used endogenous markers of GFR. In a narrative approach, we extensively review publications, primarily from the last 5 years, that address the development of methods to measure CysC, reference intervals, and the diagnostic accuracy of CysC to assess GFR. Between June 2000 and September 2001 Medline was searched using "cystatin c" as a textword, and articles that examined >75 individuals (except for renal transplant studies) and/or used accepted "gold standards" for assessing GFR were selected for inclusion. A total of 17 studies are reviewed that provide reference interval data for several populations. A total of 24 studies make conclusions about the utility of CysC vs SCr and/or creatinine clearance, with 20 providing data on the sensitivity and specificity of CysC for detecting impaired GFR. These publications are organized into subgroups that deal with specific patient populations or clinical situations. This review focuses on two areas: (a) the evolution of immunoassays used to determine the concentration of CysC in serum, their analytic sensitivity, and reference intervals; and (b) the diagnostic performance of CysC against other renal markers in the general population and in specific subpopulations of patients. Studies of reference intervals for CysC overwhelmingly demonstrated that CysC values in blood are independent of age and sex. Of the 24 studies that examined clinical utility, 15 concluded that CysC is superior to SCr, whereas 9 concluded that CysC is equivalent but provides no advantage. Summary ROC plot analysis of 20 studies that provide sensitivity and specificity data strongly suggests that CysC will be superior to SCr for detecting impaired GFR. Taken together, it is clear that CysC performs at least as well as SCr in the population at large and that it is likely to be superior to SCr in specific patient populations.
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            Measurement of residual renal function in patients treated with continuous ambulatory peritoneal dialysis.

            Renal function contributes markedly to the adequacy of continuous ambulatory peritoneal dialysis (CAPD). The best way to measure it in clinical practice has not been established. Ten stable CAPD patients with residual renal function were investigated to compare the GFR measured as inulin clearance (Cli) with the creatinine clearance (Clc), the urea clearance (Clu), and with 0.5(Clc + Clu). Thereafter, an analysis of whether the administration of cimetidine could improve the accuracy of these clearances was performed. Two clearance periods (CP) of 24 h were investigated. During CP-2, patients received 400 mg cimetidine twice daily, for a total dose of 1200 mg. Two h before the urine and dialysate collection period, inulin was administered iv. Calculations were done for each CP for Cli, Clc, Clu, Clc-Cli, the Clc/Cli ratio, and the tubular secretion of creatinine (TSc). No differences between CP-1 and CP-2 were present for urinary excretion of volume and solutes, and clearance rates of inulin and urea. The median TSc decreased from 0.71 mumol/min (range, -0.24 to 5.90) in CP-1 to 0.30 mumol/min (range, -0.18 to 0.64) in CP-2 (P < 0.05). Therefore, the median ratio of Clc/Cli decreased from 1.23 (range, 0.87 to 2.20) in CP-1 to 1.11 (range, 0.95 to 1.51) in CP-2 (P < 0.05). The median overestimation of the Cli in CP-1 by the Clc was 0.90 mL/min (range, -0.28 to 3.80) and by the 0.5(Clc + Clu) was 0.30 (range, -0.67 to 1.52). The median overestimation of Cli during cimetidine treatment in CP-2 was 0.43 mL/min (range, -0.21 to 1.20). The range, in differences between Cli and Clc, in CP-2 was smaller than that between Cli and 0.5(Clc + Clu) in CP-1. The difference between the clearance rate of inulin and creatinine or the combined clearance rate of urea and creatinine was not influenced by the magnitude of the average GFR. It can be concluded that the administration of cimetidine improved the accuracy of measuring the GFR with the Clc in CAPD patients.
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              Association of dialysis modality and cardiovascular mortality in incident dialysis patients.

              The aim of the investigation presented here was to compare the rates, causes, and timing of cardiovascular (CV) death in incident peritoneal dialysis (PD) and hemodialysis (HD) patients. The study included all adult Australian and New Zealand patients commencing dialysis between January 1, 1997 and December 31, 2007. Rates of and times to CV death were compared by incident rate ratios, cumulative incidence, and multivariable Cox proportional hazards model analyses. Dialysis modality was included in the model as a time-varying covariate, and a competing risks approach was used to obtain cause-specific hazard ratios. Of the 24,587 patients who commenced dialysis (first treatment PD n = 6521; HD n = 18,066) during the study, 5669 (21%) died from CV causes [PD 2044 (28%) versus HD 3625 (21%)]. The incidence rates of CV mortality in PD and HD patients were 9.99 and 7.96 per 100 patient-years, respectively (incidence rate ratio PD versus HD, 1.25; 95% confidence interval 1.12 to 1.32). PD was consistently associated with an increased hazard of CV death compared with HD after 1 yr of treatment. This increased risk in PD patients was largely accounted for by an increased risk of death due to myocardial infarction. Dialysis modality is significantly associated with the risk, causes, and timing of CV death experienced by ESRD patients in Australia and New Zealand.
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                Author and article information

                Journal
                J Bras Nefrol
                J Bras Nefrol
                jbn
                Jornal Brasileiro de Nefrologia
                Sociedade Brasileira de Nefrologia
                0101-2800
                2175-8239
                02 December 2019
                Jan-Mar 2020
                : 42
                : 1
                : 31-37
                Affiliations
                [1 ]Centro Hospitalar do Porto, Hospital de Santo António, Departamente de Nefrologia, Porto, Portugal.
                [2 ]Centro Hospitalar do Porto, Hospital de Santo António, Departamento de Patologia,Porto, Portugal.
                Author notes
                Correspondence to: Carla Leal Moreira. E-mail: moreira.l.s.carla@ 123456gmail.com

                AUTHOR’S CONTRIBUTION

                Carla Leal Moreira, Liliana Cunha, Sofia Correia, Filipa Silva, Ana Castro, Joana Tavares, Maria João Carvalho, José Carlos Oliveira, Olívia Santos, António Cabrita and Anabela Rodrigues contributed substantially to the conception or design of the study; collection, analysis, or interpretation of data; writing or critical review of the manuscript; and final approval of the version to be published.

                CONFLICT OF INTEREST

                We have read and understood Nephrology policy on disclosing conflicts of interest and declare that we have none.

                Author information
                http://orcid.org/0000-0002-7913-4460
                http://orcid.org/0000-0002-5271-0640
                http://orcid.org/0000-0001-5025-1658
                http://orcid.org/0000-0002-7818-6453
                http://orcid.org/0000-0001-8328-2805
                http://orcid.org/0000-0002-3776-4923
                http://orcid.org/0000-0003-4374-2867
                http://orcid.org/0000-0003-2142-6839
                http://orcid.org/0000-0002-0193-3625
                http://orcid.org/0000-0003-3794-9239
                http://orcid.org/0000-0001-8818-2141
                Article
                10.1590/2175-8239-JBN-2019-0007
                7213933
                31799980
                a639ebf5-667d-4b6e-88d9-8c6bfe72f3a1

                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.

                History
                : 09 January 2019
                : 06 June 2019
                Categories
                Original Articles

                cystatin c,cardiovascular diseases,peritoneal dialysis,cistatina c,doenças cardiovasculares,diálise peritoneal

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