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Creatinine Versus Cystatin C: Differing Estimates of Renal Function in Hospitalized Veterans Receiving Anticoagulants.

ABSTRACT: BACKGROUND:Current practice in anticoagulation dosing relies on kidney function estimated by serum creatinine using the Cockcroft-Gault equation. However, creatinine can be unreliable in patients with low or high muscle mass. Cystatin C provides an alternative estimation of glomerular filtration rate (eGFR) that is independent of muscle. OBJECTIVE:We compared cystatin C-based eGFR (eGFRcys) with multiple creatinine-based estimates of kidney function in hospitalized patients receiving anticoagulants, to assess for discordant results that could impact medication dosing. DESIGN:Retrospective chart review of hospitalized patients over 1 year who received non-vitamin K antagonist anticoagulation, and who had same-day measurements of cystatin C and creatinine. PARTICIPANTS:Seventy-five inpatient veterans (median age 68) at the San Francisco VA Medical Center (SFVAMC). MAIN MEASURES:We compared the median difference between eGFR by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) study equation using cystatin C (eGFRcys) and eGFRs using three creatinine-based equations: CKD-EPI (eGFREPI), Modified Diet in Renal Disease (eGFRMDRD), and Cockcroft-Gault (eGFRCG). We categorized patients into standard KDIGO kidney stages and into drug-dosing categories based on each creatinine equation and calculated proportions of patients reclassified across these categories based on cystatin C. KEY RESULTS:Cystatin C predicted overall lower eGFR compared to creatinine-based equations, with a median difference of -?7.1 (IQR -?17.2, 2.6) mL/min/1.73 m2 versus eGFREPI, -?21.2 (IQR -?43.7, -?8.1) mL/min/1.73 m2 versus eGFRMDRD, and -?25.9 (IQR -?46.8, -?8.7) mL/min/1.73 m2 versus eGFRCG. Thirty-one to 52% of patients were reclassified into lower drug-dosing categories using cystatin C compared to creatinine-based estimates. CONCLUSIONS:We found substantial discordance in eGFR comparing cystatin C with creatinine in this group of anticoagulated inpatients. Our sample size was limited and included few women. Further investigation is needed to confirm these findings and evaluate implications for bleeding and other clinical outcomes. NIH TRIAL REGISTRY NUMBER:Not applicable.

SUBMITTER: Wang CH

PROVIDER: S-EPMC6082212 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Creatinine Versus Cystatin C: Differing Estimates of Renal Function in Hospitalized Veterans Receiving Anticoagulants.

Wang Christina Hao CH Rubinsky Anna D AD Minichiello Tracy T Shlipak Michael G MG Price Erika Leemann EL

Journal of general internal medicine 20180531 8

<h4>Background</h4>Current practice in anticoagulation dosing relies on kidney function estimated by serum creatinine using the Cockcroft-Gault equation. However, creatinine can be unreliable in patients with low or high muscle mass. Cystatin C provides an alternative estimation of glomerular filtration rate (eGFR) that is independent of muscle.<h4>Objective</h4>We compared cystatin C-based eGFR (eGFR<sub>cys</sub>) with multiple creatinine-based estimates of kidney function in hospitalized pati ...[more]

PMID: 29855865

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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:The US prevalence of reduced estimated glomerular filtration rate (eGFR) based on serum creatinine level increased during the decade ending in 2002. National Health and Nutrition Examination Survey (NHANES) cystatin C measurements recently were calibrated to the international standard, allowing for an independent test of the trend in prevalence of reduced eGFR using cystatin C level.Cross-sectional surveys performed during 2 periods.Nationally representative subsamples of adult participants from NHANES III (1988-1994) and the NHANES 1999-2002 surveys.Survey period.Prevalence of reduced GFR, defined as eGFR <60 mL/min/1.73 m² based on levels of serum creatinine, cystatin C, or both (eGFRcr, eGFRcys, and eGFRcr-cys), using estimating equations developed by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI).Serum cystatin C level, measured from stored samples in 2006, calibrated to the international standard in 2012.Between 1988-1994 and 1999-2002, the prevalence of reduced eGFRcr, eGFRcys, and eGFRcr-cys increased from 4.7% (95% CI, 4.1%-5.3%) to 6.5% (95% CI, 5.9%-7.1%) (P < 0.001), from 5.5% (95% CI, 4.6%-6.5%) to 8.7% (95% CI, 7.5%-10.0%) (P < 0.001), and from 4.4% (95% CI, 3.7%-5.2%) to 7.1% (95% CI, 6.2%-8.0%) (P < 0.001), respectively. The higher prevalence of reduced GFR in the later period was observed in all subgroups of age, race, sex, and GFR categories. After adjusting for changes in the US population by age, sex, race, diabetes, hypertension, and body mass index, prevalence ratios of reduced GFR in the later versus earlier survey were 1.24 (95% CI, 1.09-1.45), 1.34 (95% CI, 1.15-1.67), and 1.33 (95% CI, 1.17-1.65) using eGFRcr, eGFRcys, and eGFRcr-cys, respectively.Likely underascertainment of persons with GFR <15 mL/min/1.73 m²; GFR was estimated and not measured; comparability of laboratory assays based on a calibration subsample.The prevalence of reduced eGFRcys in the US civilian noninstitutionalized population increased between 1988-1994 and 1999-2002, confirming the increase observed in the prevalence of reduced eGFRcr.

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Creatinine Versus Cystatin C: Differing Estimates of Renal Function in Hospitalized Veterans Receiving Anticoagulants.

Publications

Creatinine Versus Cystatin C: Differing Estimates of Renal Function in Hospitalized Veterans Receiving Anticoagulants.

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