Risk of ESRD and Mortality Associated With Change in Filtration Markers

Casey M. Rebholz, Lesley A. Inker, Yuan Chen, Menglu Liang, Meredith C. Foster, John H. Eckfeldt, Paul L. Kimmel, Ramachandran S. Vasan, Harold I. Feldman, Mark J. Sarnak, Chi yuan Hsu, Andrew S. Levey, Josef Coresh

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)551-560
Number of pages10
JournalAmerican Journal of Kidney Diseases
Volume70
Issue number4
DOIs
StatePublished - Oct 2017

Bibliographical note

Funding 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.

Publisher Copyright:
© 2017 National Kidney Foundation, Inc.

Keywords

  • Beta-2-microglobulin (B2M)
  • beta trace protein (BTP)
  • creatinine
  • cystatin C
  • death
  • end-stage renal disease (ESRD)
  • estimated GFR
  • filtration markers
  • glomerular filtration rate (GFR)
  • incident ESRD
  • kidney function decline
  • measured GFR
  • mortality

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