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    ABSTRACT: Abstract Background: Despite standard laboratory quality control, drift and day-to-day variability in cystatin C measurements can be observed. We investigated whether correction for drift and day-to-day variation in cystatin C measurements improves the association of estimated glomerular filtration rate (eGFR) with chronic kidney disease (CKD) risk factors and prognosis. Methods: Plasma samples of the PREVEND study (Dutch cohort study, n=8592) were used to measure cystatin C (Gentian assay) on 243 random days. A correction factor was calculated for each measurement day. GFR was estimated with CKD-EPI equation using routinely measured cystatin C (eGFRcysC) and corrected cystatin C (eGFRcysC corr). Participants were categorized in six categories of eGFRcysC and eGFRcysC corr: ≥120, 90-119, 75-89, 60-74, 45-59 and <45 mL/min/1.73m2. Independent replication was performed in the ESTHER study (German cohort study, n=9949). Results: Compared to non-reclassified participants, participants re-classified upward had significantly lower age, body mass index, blood pressure, cholesterol, glucose and albuminuria, whereas the opposite was true for participants reclassified downward. CKD risk factors explained more variance in eGFRcysC corr than in eGFRcysC (p<0.001). Compared to non-reclassified participants, risk of incident cardiovascular events (n=789, follow-up 9.3±2.7 years) tended to be higher in downward reclassified and lower in upward reclassified participants. Net reclassification improvement for incident cardiovascular events using eGFRcysC corr was positive (0.102, p=0.019). The ESTHER study showed similar results. Conclusions: Correction for drift and day-to-day variation in cystatin C measurement improves eGFR using cystatin C for its association with CKD risk factors and incident cardiovascular events.
    Clinical Chemistry and Laboratory Medicine 11/2014; DOI:10.1515/cclm-2014-0894 · 2.96 Impact Factor
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    ABSTRACT: The effects of antiretrovirals on cystatin C-based renal function estimates are unknown. We analyzed changes in renal function using creatinine and cystatin C-based estimating equations in 269 patients in A5224s, a substudy of study A5202, in which treatment-naive patients were randomized to abacavir/lamivudine or tenofovir/emtricitabine with open-label atazanavir/ritonavir or efavirenz. Changes in renal function significantly improved (or declined less) with abacavir/lamivudine treatment compared with tenofovir/emtricitabine using the Cockcroft-Gault formula (P = .016) and 2009 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI; P = .030) and 2012 CKD-EPI cystatin C-creatinine (P = .025). Renal function changes significantly improved (or declined less) with efavirenz compared with atazanavir/ritonavir (P < .001 for all equations). Mean (95% confidence interval) renal function changes specifically for tenofovir/emtricitabine combined with atazanavir/ritonavir were -8.3 (-14.0, -2.6) mL/min with Cockcroft-Gault; -14.9 (-19.7, -10.1) mL/min per 1.73(2) with Modification of Diet in Renal Disease; -12.8 (-16.5, -9.0) mL/min per 1.73(2) with 2009 CKD-EPI; +8.9 (4.2, 13.7) mL/min per 1.73(2) with 2012 CKD-EPI cystatin C; and -1.2 (-5.1, 2.6) mL/min per 1.73(2) with 2012 CKD-EPI cystatin C-creatinine. Renal function changes for the other treatment arms were more favorable but similarly varied by estimating equation. Antiretroviral-associated changes in renal function vary in magnitude and direction based on the estimating equation used.
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    ABSTRACT: 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.Conclusions Proximal 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.
    Clinical Journal of the American Society of Nephrology 11/2014; 10(1). DOI:10.2215/CJN.03220314 · 5.25 Impact Factor