Background Using change in estimated glomerular filtration rate (eGFR) based on creatinine concentration as a surrogate outcome in clinical trials of chronic kidney disease has been proposed. Risk for end-stage renal disease (ESRD) and all-cause mortality associated with change in concentrations of other filtration markers has not been studied in chronic kidney disease populations. Study Design Observational analysis of 2 clinical trials. Setting & Participants Participants in the MDRD (Modification of Diet in Renal Disease; n = 317) Study and AASK (African American Study of Kidney Disease and Hypertension; n = 373). Predictors Creatinine, cystatin C, β-trace protein (BTP), and β2-microglobulin (B2M) were measured in serum samples collected at the 12- and 24-month follow-up visits, along with measured GFR (mGFR) at these time points. Outcomes ESRD and all-cause mortality. Measurements Poisson regression was used to estimate incidence rate ratios and 95% CIs for ESRD and all-cause mortality during long-term follow-up (10-16 years) per 30% decline in mGFR or eGFR for each filtration marker and the average of all 4 markers. Results 1-year decline in mGFR, eGFRcr, eGFRBTP, and the average of the 4 filtration markers was significantly associated with increased risk for incident ESRD in both studies (all P ≤ 0.02). Compared to mGFR, only decline in eGFRBTP was statistically significantly more strongly associated with ESRD risk in both studies (both P ≤ 0.03). Decline in eGFRcr, but not mGFR or the other filtration markers, was significantly associated with risk for all-cause mortality in AASK only (incidence rate ratio per 30% decline, 4.17; 95% CI, 1.78-9.74; P < 0.001), but this association was not significantly different from decline in mGFR (P = 0.2). Limitations Small sample size. Conclusions Declines in mGFR, eGFRcr, eGFRBTP, and the average of 4 filtration markers (creatinine, cystatin C, BTP, and B2M) were consistently associated with progression to ESRD.
Bibliographical noteFunding Information:
Support: Research was supported by the CKD Biomarkers Consortium, funded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK; U01 DK085689 ). Dr Rebholz is supported by a grant from the NIDDK ( K01 DK107782 ). Some of the data reported here have been supplied by the US Renal Data System. The funders had no role in the study designs; collection, analysis, and interpretation of the data; writing the report; and the decision to submit the report for publication.
© 2017 National Kidney Foundation, Inc.
- Beta-2-microglobulin (B2M)
- beta trace protein (BTP)
- cystatin C
- end-stage renal disease (ESRD)
- estimated GFR
- filtration markers
- glomerular filtration rate (GFR)
- incident ESRD
- kidney function decline
- measured GFR