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Glomerular filtration rate estimated using creatinine, cystatin C or both markers and the risk of clinical events in HIV-infected individuals.

ABSTRACT: The accuracy and precision of glomerular filtration rate (GFR) estimating equations based on plasma creatinine (GFR(cr)), cystatin C (GFR(cys)) and the combination of these markers (GFR(cr-cys)) have recently been assessed in HIV-infected individuals. We assessed the associations of GFR, estimated by these three equations, with clinical events in HIV-infected individuals.We compared the associations of baseline GFR(cr), GFR(cys) and GFR(cr-cys) [using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations] with mortality, cardiovascular events (CVEs) and opportunistic diseases (ODs) in the Strategies for the Management of Antiretroviral Therapy (SMART) study. We used Cox proportional hazards models to estimate unadjusted and adjusted hazard ratios per standard deviation (SD) change in GFR.A total of 4614 subjects from the SMART trial with available baseline creatinine and cystatin C data were included in this analysis. Of these, 99 died, 111 had a CVE and 121 had an OD. GFR(cys) was weakly to moderately correlated with HIV RNA, CD4 cell count, high-sensitivity C-reactive protein, interleukin-6, and D-dimer, while GFR(cr) had little or no correlation with these factors. GFR(cys) had the strongest associations with the three clinical outcomes, followed closely by GFR(cr-cys), with GFR(cr) having the weakest associations with clinical outcomes. In a model adjusting for demographics, cardiovascular risk factors, HIV-related factors and inflammation markers, a 1-SD lower GFR(cys) was associated with a 55% [95% confidence interval (CI) 27-90%] increased risk of mortality, a 21% (95% CI 0-47%) increased risk of CVE, and a 22% (95% CI 0-48%) increased risk of OD.Of the three CKD-EPI GFR equations, GFR(cys) had the strongest associations with mortality, CVE and OD.

SUBMITTER: Lucas GM

PROVIDER: S-EPMC3947332 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature

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Glomerular filtration rate estimated using creatinine, cystatin C or both markers and the risk of clinical events in HIV-infected individuals.

Lucas G M GM Cozzi-Lepri A A Wyatt C M CM Post F A FA Bormann A M AM Crum-Cianflone N F NF Ross M J MJ

HIV medicine 20130911 2

<h4>Objectives</h4>The accuracy and precision of glomerular filtration rate (GFR) estimating equations based on plasma creatinine (GFR(cr)), cystatin C (GFR(cys)) and the combination of these markers (GFR(cr-cys)) have recently been assessed in HIV-infected individuals. We assessed the associations of GFR, estimated by these three equations, with clinical events in HIV-infected individuals.<h4>Methods</h4>We compared the associations of baseline GFR(cr), GFR(cys) and GFR(cr-cys) [using the Chron ...[more]

PMID: 24024499

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Project description:BACKGROUND:The Kidney Disease Improving Global Outcomes (KDIGO) guideline recommends use of a cystatin C-based estimated glomerular filtration rate (eGFR) to confirm creatinine-based eGFR between 45 and 59 mL · min(-1) · (1.73 m(2))(-1). Prior studies have demonstrated that comorbidities such as solid-organ transplant strongly influence the relationship between measured GFR, creatinine, and cystatin C. Our objective was to evaluate the performance of cystatin C-based eGFR equations compared with creatinine-based eGFR and measured GFR across different clinical presentations. METHODS:We compared the performance of the CKD-EPI 2009 creatinine-based estimated GFR equation (eGFRCr) and the newer CKD-EPI 2012 cystatin C-based equations (eGFRCys and eGFRCr-Cys) with measured GFR (iothalamate renal clearance) across defined patient populations. Patients (n = 1652) were categorized as transplant recipients (n = 568 kidney; n = 319 other organ), known chronic kidney disease (CKD) patients (n = 618), or potential kidney donors (n = 147). RESULTS:eGFRCr-Cys showed the most consistent performance across different clinical populations. Among potential kidney donors without CKD [stage 2 or higher; eGFR >60 mL · min(-1) · (1.73 m(2))(-1)], eGFRCys and eGFRCr-Cys demonstrated significantly less bias than eGFRCr; however, all 3 equations substantially underestimated GFR when eGFR was <60 mL · min(-1) · (1.73 m(2))(-1). Among transplant recipients with CKD stage 3B or greater [eGFR <45 mL · min(-1) · (1.73 m(2))(-1)], eGFRCys was significantly more biased than eGFRCr. No clear differences in eGFR bias between equations were observed among known CKD patients regardless of eGFR range or in any patient group with a GFR between 45 and 59 mL · min(-1) · (1.73 m(2))(-1). CONCLUSIONS:The performance of eGFR equations depends on patient characteristics that are readily apparent on presentation. Among the 3 CKD-EPI equations, eGFRCr-Cys performed most consistently across the studied patient populations.

Project description:Estimates of glomerular filtration rate (GFR) that are based on serum creatinine are routinely used; however, they are imprecise, potentially leading to the overdiagnosis of chronic kidney disease. Cystatin C is an alternative filtration marker for estimating GFR.Using cross-sectional analyses, we developed estimating equations based on cystatin C alone and in combination with creatinine in diverse populations totaling 5352 participants from 13 studies. These equations were then validated in 1119 participants from 5 different studies in which GFR had been measured. Cystatin and creatinine assays were traceable to primary reference materials.Mean measured GFRs were 68 and 70 ml per minute per 1.73 m(2) of body-surface area in the development and validation data sets, respectively. In the validation data set, the creatinine-cystatin C equation performed better than equations that used creatinine or cystatin C alone. Bias was similar among the three equations, with a median difference between measured and estimated GFR of 3.9 ml per minute per 1.73 m(2) with the combined equation, as compared with 3.7 and 3.4 ml per minute per 1.73 m(2) with the creatinine equation and the cystatin C equation (P=0.07 and P=0.05), respectively. Precision was improved with the combined equation (interquartile range of the difference, 13.4 vs. 15.4 and 16.4 ml per minute per 1.73 m(2), respectively [P=0.001 and P<0.001]), and the results were more accurate (percentage of estimates that were >30% of measured GFR, 8.5 vs. 12.8 and 14.1, respectively [P<0.001 for both comparisons]). In participants whose estimated GFR based on creatinine was 45 to 74 ml per minute per 1.73 m(2), the combined equation improved the classification of measured GFR as either less than 60 ml per minute per 1.73 m(2) or greater than or equal to 60 ml per minute per 1.73 m(2) (net reclassification index, 19.4% [P<0.001]) and correctly reclassified 16.9% of those with an estimated GFR of 45 to 59 ml per minute per 1.73 m(2) as having a GFR of 60 ml or higher per minute per 1.73 m(2).The combined creatinine-cystatin C equation performed better than equations based on either of these markers alone and may be useful as a confirmatory test for chronic kidney disease. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases.).

Project description:ImportanceAs cystatin C is increasingly adopted to estimate glomerular filtration rate (eGFR), clinicians will encounter patients in whom cystatin C-based eGFR (eGFRcys) and creatinine-based eGFR (eGFRcr) differ widely. The clinical implications of these differences, eGFRdiffcys-cr, are unknown.ObjectiveTo evaluate the associations of eGFRdiffcys-cr with end-stage kidney disease (ESKD) and mortality among individuals with chronic kidney disease (CKD).Design, setting, and participantsThis is a prospective cohort study of 4956 individuals with mild to moderate CKD from 7 clinical centers in the United States who enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study between 2003 to 2018. Statistical analyses were completed in December 2021.ExposureseGFRdiffcys-cr (eGFRcys - eGFRcr) was calculated at baseline and annually thereafter for 3 years. Because 15 mL/min/1.73 m2 represents a clinically meaningful difference in eGFR that also distinguishes CKD stages, eGFRdiffcys-cr was categorized as: less than -15 mL/min/1.73 m2, -15 to 15 mL/min/1.73 m2, and 15 mL/min/1.73 m2 or greater.Main outcomes and measuresThe outcomes of ESKD, defined as initiation of maintenance dialysis or receipt of a kidney transplant, and all-cause mortality were adjudicated from study entry until administrative censoring in 2018.ResultsAmong 4956 participants with mean (SD) age of 59.5 (10.5) years, 2152 (43.4%) were Black, 515 (10.4%) were Hispanic, and 2113 (42.6%) were White. There were 2156 (43.5%) women and 2800 (56.5%) men. At baseline, eGFRcys and eGFRcr values differed by more than 15 mL/min/1.73 m2 in one-third of participants (1638 participants [33.1%]). Compared with participants with similar baseline eGFRcys and eGFRcr (eGFRdiffcys-cr -15 to 15 mL/min/1.73 m2), those in whom eGFRcys was substantially lower than eGFRcr (eGFRdiffcys-cr < -15 mL/min/1.73 m2) had a higher risk of mortality (hazard ratio [HR], 1.86; 95% CI, 1.40-2.48) while those with eGFRdiffcys-cr of 15 mL/min/1.73 m2 or greater had lower risks of ESKD (subHR [SHR], 0.73; 95% CI, 0.59-0.89) and mortality (HR, 0.68; 95% CI, CI 0.58-0.81). In time-updated analyses, participants with eGFRdiffcys-cr less than -15 mL/min/1.73 m2 had higher risks of ESKD (SHR, 1.83; 95% CI, 1.10-3.04) and mortality (HR, 3.03; 95% CI, 2.19-4.19) compared with participants with similar eGFRcys and eGFRcr. Conversely, participants with eGFRdiffcys-cr of 15 mL/min/1.73 m2 or greater had lower risks of ESKD (SHR, 0.50; 95% CI, 0.35-0.71) and mortality (HR, 0.58; 95% CI, 0.45-0.75). Longitudinal changes in eGFRdiffcys-cr were associated with mortality risk. Compared with participants who had similar slopes by eGFRcys and eGFRcr, those with smaller eGFRcr declines had an 8-fold increased mortality risk (HR, 8.20; 95% CI, 6.37-10.56), and those with larger apparent declines by eGFRcr had a lower mortality risk (HR, 0.14; 95% CI, 0.08-0.24).Conclusions and relevanceThese findings suggest that large differences between eGFRcys and eGFRcr were common in persons with CKD. These differences and their changes over time may be informative of ESKD and mortality risks, warranting monitoring of both eGFRcys and eGFRcr in this high-risk population.

Project description:BackgroundWe recently published and validated the new serum creatinine (Scr)-based full-age-spectrum equation (FAS crea ) for estimating the glomerular filtration rate (GFR) for healthy and kidney-diseased subjects of all ages. The equation was based on the concept of normalized Scr and shows equivalent to superior prediction performance to the currently recommended equations for children, adolescents, adults and older adults.MethodsBased on an evaluation of the serum cystatin C (ScysC) distribution, we defined normalization constants for ScysC ( Q cysC = 0.82 mg/L for ages <70 years and Q cysC = 0.95 mg/L for ages ≥70 years). By replacing Scr/ Q crea in the FAS crea equation with ScysC/ Q cysC , or with the average of both normalized biomarkers, we obtained new ScysC-based (FAS cysC ) and combined Scr-/ScysC-based FAS equations (FAS combi ). To validate the new FAS cysC and FAS combi we collected data on measured GFR, Scr, ScysC, age, gender, height and weight from 11 different cohorts including n = 6132 unique white subjects (368 children, aged ≤18 years, 4295 adults and 1469 older adults, aged ≥70 years).ResultsIn children and adolescents, the new FAS cysC equation showed significantly better performance [percentage of patients within 30% of mGFR (P30) = 86.1%] than the Caucasian Asian Paediatric Adult Cohort equation (P30 = 76.6%; P < 0.0001), or the ScysC-based Schwartz equation (P30 = 68.8%; P < 0.0001) and the FAS combi equation outperformed all equations with P30 = 92.1% (P < 0.0001). In adults, the FAS cysC equation (P30 = 82.6%) performed equally as well as the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI cysC ) (P30 = 80.4%) and the FAS combi equation (P30 = 89.9%) was also equal to the combined CKD-EPI equation (P30 = 88.2%). In older adults, FAS cysC was superior (P30 = 88.2%) to CKD-EPI cysC (P30 = 84.4%; P < 0.0001) and the FAS combi equation (P30 = 91.2%) showed significantly higher performance than the combined CKD-EPI equation (P30 = 85.6%) (P < 0.0001).ConclusionThe FAS equation is not only applicable to all ages, but also for all recommended renal biomarkers and their combinations.

Dataset Information

Glomerular filtration rate estimated using creatinine, cystatin C or both markers and the risk of clinical events in HIV-infected individuals.

Publications

Glomerular filtration rate estimated using creatinine, cystatin C or both markers and the risk of clinical events in HIV-infected individuals.

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