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Comparisons of creatinine and cystatin C for detection of kidney disease and prediction of all-cause mortality in HIV-infected women.

ABSTRACT: Cystatin C could improve chronic kidney disease (CKD) classification in HIV-infected women relative to serum creatinine.Retrospective cohort analysis.Cystatin C and creatinine were measured from specimens taken and stored during the 1999-2000 examination among 908 HIV-infected participants in the Women's Interagency HIV study (WIHS). Mean follow-up was 10.2 years. Predictors of differential glomerular filtration rate (GFR) estimates were evaluated with multivariable linear regression. The associations of baseline categories (<60, 60-90, and >90?ml/min per 1.73?m) of creatinine estimated GFR (eGFRcr), cystatin C eGFR (eGFRcys), and combined creatinine-cystatin C eGFR (eGFRcr-cys) with all-cause mortality were evaluated using multivariable Cox regression. The net reclassification index (NRI) was calculated to evaluate the effect of cystatin C on reclassification of CKD staging.CKD risk factors were associated with lower eGFRcys and eGFRcr-cys values compared with eGFRcr. Relative to eGFR more than 90, the eGFR less than 60 category by eGFRcys (Adjusted hazard ratio: 2.56; 95% confidence interval: 1.63-4.02), eGFRcr-cys (3.11; 1.94-5.00), and eGFRcr (2.34; 1.44-3.79) was associated with increased mortality risk. However, the eGFR 60-90 category was associated with increased mortality risk for eGFRcys (1.80; 1.28-2.53) and eGFRcr-cys (1.91; 1.38-2.66) but not eGFRcr (1.20; 0.85-1.67). The overall NRI for mortality was 26% when reclassifying from eGFRcr to eGFRcys (P?

SUBMITTER: Driver TH

PROVIDER: S-EPMC3919542 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature

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Comparisons of creatinine and cystatin C for detection of kidney disease and prediction of all-cause mortality in HIV-infected women.

Driver Todd H TH Scherzer Rebecca R Peralta Carmen A CA Tien Phyllis C PC Estrella Michelle M MM Parikh Chirag R CR Butch Anthony W AW Anastos Kathryn K Cohen Mardge H MH Nowicki Marek M Sharma Anjali A Young Mary A MA Abraham Alison A Shlipak Michael G MG

AIDS (London, England) 20130901 14

<h4>Background</h4>Cystatin C could improve chronic kidney disease (CKD) classification in HIV-infected women relative to serum creatinine.<h4>Design</h4>Retrospective cohort analysis.<h4>Methods</h4>Cystatin C and creatinine were measured from specimens taken and stored during the 1999-2000 examination among 908 HIV-infected participants in the Women's Interagency HIV study (WIHS). Mean follow-up was 10.2 years. Predictors of differential glomerular filtration rate (GFR) estimates were evaluate ...[more]

PMID: 23669156

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Project description:Compared with controls, human immunodeficiency virus (HIV)-infected persons have a greater prevalence of kidney disease, assessed according to high cystatin C level and albuminuria, but not according to creatinine level. However, the clinical importance of increased cystatin C level and albuminuria in the HIV-infected population has not been studied.We conducted an observational cohort study to determine the association of kidney disease (measured according to albuminuria, cystatin C, and serum creatinine) with mortality.922 HIV-infected persons enrolled in the FRAM (Fat Redistribution and Metabolic Change in HIV Infection) Study.Serum cystatin C and serum creatinine levels were used to estimate glomerular filtration rates (eGFR(SCysC) and eGFR(SCr), respectively). Albuminuria was defined as a positive urine dipstick result (? 1+) or urine albumin-creatinine ratio >30 mg/g.5-Year mortality.At baseline, decreased kidney function (eGFR(SCysC) <60 mL/min/1.73 m(2)) or albuminuria was present in 28% of participants. After 5 years of follow-up, mortality was 48% in those with both eGFR(SCysC) < 60 mL/min/1.73 m(2) and albuminuria, 23% in those with eGFR(SCysC) < 60 mL/min/1.73 m(2) alone, 20% in those with albuminuria alone, and 9% in those with neither condition. After multivariable adjustment for demographics, cardiovascular risk factors, HIV-related factors, and inflammatory marker levels, eGFR(SCysC) < 60 mL/min/1.73 m(2) and albuminuria were associated with a nearly 2-fold increase in mortality, whereas eGFR(SCr) < 60 mL/min/1.73 m(2) did not appear to have a substantial association with mortality. Together, eGFR(SCysC) <60 mL/min/1.73 m(2) and albuminuria accounted for 17% of the population-level attributable risk of mortality.Vital status was unknown in 261 participants from the original cohort.Kidney disease marked by albuminuria or increased cystatin C level appears to be an important risk factor for mortality in HIV-infected individuals. A substantial proportion of this risk may be unrecognized because of the current reliance on serum creatinine to estimate kidney function in clinical practice.

Project description:BackgroundAlthough individual urine biomarkers are associated with chronic kidney disease (CKD) incidence and all-cause mortality in the setting of HIV infection, their combined utility for prediction remains unknown.MethodsWe measured eight urine biomarkers shown previously to be associated with incident CKD and mortality risk among 902 HIV-infected women in the Women's Interagency HIV Study: N-acetyl-β-d-glucosaminidase (NAG), kidney injury molecule-1 (KIM-1), alpha-1 microglobulin (α1m), interleukin 18, neutrophil gelatinase-associated lipocalin, albumin-to-creatinine ratio, liver fatty acid-binding protein and α-1-acid-glycoprotein. A group-based cluster method classified participants into three distinct clusters using the three most distinguishing biomarkers (NAG, KIM-1 and α1m), independent of the study outcomes. We then evaluated associations of each cluster with incident CKD (estimated glomerular filtration rate <60 mL/min/1.73 m(2) by cystatin C) and all-cause mortality, adjusting for traditional and HIV-related risk factors.ResultsOver 8 years of follow-up, 177 CKD events and 128 deaths occurred. The first set of clusters partitioned women into three groups, containing 301 (Cluster 1), 470 (Cluster 2) and 131 (Cluster 3) participants. The rate of CKD incidence was 13, 21 and 50% across the three clusters; mortality rates were 7.3, 13 and 34%. After multivariable adjustment, Cluster 3 remained associated with a nearly 3-fold increased risk of both CKD and mortality, relative to Cluster 1 (both P < 0.001). The addition of the multi-biomarker cluster to the multivariable model improved discrimination for CKD (c-statistic = 0.72-0.76, P = 0.0029), but only modestly for mortality (c = 0.79-0.80, P = 0.099). Clusters derived with all eight markers were no better for discrimination than the three-biomarker clusters.ConclusionsFor predicting incident CKD in HIV-infected women, clusters developed from three urine-based kidney disease biomarkers were as effective as an eight-marker panel in improving risk discrimination.

Project description:BACKGROUND:Estimated glomerular filtration rate (eGFR) is routinely utilized as a measure of renal function. While creatinine-based eGFR (eGFRcr) is widely used in clinical practice, the use of cystatin-C to estimate GFR (eGFRcys) has demonstrated superior risk prediction in various populations. Prior studies that derived eGFR formulas have infrequently included high proportions of elderly, African-Americans, and Hispanics. OBJECTIVE:Our objective as to compare mortality risk prediction using eGFRcr and eGFRcys in an elderly, race/ethnically diverse population. DESIGN:The Northern Manhattan Study (NOMAS) is a multiethnic prospective cohort of elderly stroke-free individuals consisting of a total of 3,298 participants recruited between 1993 and 2001, with a median follow-up of 18 years. PARTICIPANTS:We included all Northern Manhattan Study (NOMAS) participants with concurrent measured creatinine and cystatin-C. MAIN MEASURES:The eGFRcr was calculated using the CKD-EPI 2009 equation. eGFRcys was calculated using the CKD-EPI 2012 equations. The performance of each eGFR formula in predicting mortality risk was tested using receiver-operating characteristics, calibration and reclassification. Net reclassification improvement (NRI) was calculated based on the Reynolds 10 year risk score from adjusted Cox models with mortality as an outcome. The primary hypothesis was that eGFRcys would better predict mortality than eGFRcr. RESULTS:Participants (n = 2988) had a mean age of 69±10.2 years and were predominantly Hispanic (53%), overweight (69%), and current or former smokers (53% combined). The mean eGFRcr (74.68±18.8 ml/min/1.73m2) was higher than eGFRcys (51.72±17.2 ml/min/1.73m2). During a mean of 13.0±5.6 years of follow-up, 53% of the cohort had died. The AUC of eGFRcys (0.73) was greater than for eGFRcr (0.67, p for difference<0.0001). The proportions of correct reclassification (NRI) based on 10 year mortality for the model with eGFRcys compared to the model with eGFRcr were 4.2% (p = 0.002). CONCLUSIONS:In an elderly, race/ethnically diverse cohort low eGFR is associated with risk of all-cause mortality. Estimated GFR based on serum cystatin-C, in comparison to serum creatinine, was a better predictor of all-cause mortality.

Project description:BACKGROUND:Adding the measurement of cystatin C to that of serum creatinine to determine the estimated glomerular filtration rate (eGFR) improves accuracy, but the effect on detection, staging, and risk classification of chronic kidney disease across diverse populations has not been determined. METHODS:We performed a meta-analysis of 11 general-population studies (with 90,750 participants) and 5 studies of cohorts with chronic kidney disease (2960 participants) for whom standardized measurements of serum creatinine and cystatin C were available. We compared the association of the eGFR, as calculated by the measurement of creatinine or cystatin C alone or in combination with creatinine, with the rates of death (13,202 deaths in 15 cohorts), death from cardiovascular causes (3471 in 12 cohorts), and end-stage renal disease (1654 cases in 7 cohorts) and assessed improvement in reclassification with the use of cystatin C. RESULTS:In the general-population cohorts, the prevalence of an eGFR of less than 60 ml per minute per 1.73 m(2) of body-surface area was higher with the cystatin C-based eGFR than with the creatinine-based eGFR (13.7% vs. 9.7%). Across all eGFR categories, the reclassification of the eGFR to a higher value with the measurement of cystatin C, as compared with creatinine, was associated with a reduced risk of all three study outcomes, and reclassification to a lower eGFR was associated with an increased risk. The net reclassification improvement with the measurement of cystatin C, as compared with creatinine, was 0.23 (95% confidence interval [CI], 0.18 to 0.28) for death and 0.10 (95% CI, 0.00 to 0.21) for end-stage renal disease. Results were generally similar for the five cohorts with chronic kidney disease and when both creatinine and cystatin C were used to calculate the eGFR. CONCLUSIONS:The use of cystatin C alone or in combination with creatinine strengthens the association between the eGFR and the risks of death and end-stage renal disease across diverse populations. (Funded by the National Kidney Foundation and others.).

Project description:Background and objectivesDespite advances in therapy, HIV-infected individuals remain at higher risk for kidney dysfunction than uninfected individuals. It was hypothesized that urine levels of ?1-microglobulin, a biomarker of proximal tubular dysfunction, would predict kidney function decline and mortality risk in HIV-infected and uninfected women.Design, setting, participants, & measurementsIn the Women's Interagency HIV Study, urine ?1-microglobulin and creatinine concentrations were measured in 903 HIV-infected and 287 uninfected women using stored urine from 1999 to 2000, when prevalence of tenofovir use was <1%. Participants were categorized into three categories by level of ?1-microglobulin-to-creatinine ratio, and associations with kidney decline and all-cause mortality over 8 years were evaluated.ResultsUrine ?1-microglobulin was detectable in 60% of HIV-infected and 40% of uninfected women (P<0.001). Among HIV-infected women, there were 177 (22%), 61 (7%), and 128 (14%) patients with incident CKD, with 10% annual eGFR decline, and who died, respectively. Compared with HIV-infected women in the lowest ?1-microglobulin category, HIV-infected women in the highest ?1-microglobulin category had a 2.1-fold risk of incident CKD (95% confidence interval, 1.3 to 3.4), 2.7-fold risk of 10% annual eGFR decline (95% confidence interval, 1.2 to 5.9), and 1.6-fold mortality risk (95% confidence interval, 1.0 to 2.6) in models adjusting for kidney risk factors, baseline eGFR, and albuminuria. Among uninfected women, the highest ?1-microglobulin category was associated with 3% (relative risk, 2.2; 95% confidence interval, 1.4 to 3.5) and 5% (relative risk, 2.2; 95% confidence interval, 1.1 to 4.3) annual eGFR decline relative to the lowest ?1-microglobulin category.ConclusionsProximal tubular dysfunction, indicated by urine ?1-microglobulin, was independently associated with kidney function decline in HIV-infected and uninfected women and mortality risk among HIV-infected women.

Dataset Information

Comparisons of creatinine and cystatin C for detection of kidney disease and prediction of all-cause mortality in HIV-infected women.

Publications

Comparisons of creatinine and cystatin C for detection of kidney disease and prediction of all-cause mortality in HIV-infected women.

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