Interaction between GFR and risk factors for morbidity and mortality in African Americans with CKD

Abstract

Background and objectives: The African American Study of Kidney Disease Trial identified risk factors for CKD progression and suggested that GFR level may modify the association between these risk factors and CKD progression or death.

Design, setting, participants, & measurements: Enrollment in the African American Study of Kidney Disease Trial occurred between June of 1995 and September of 2001, with median follow-up of 48.6 months. Among 1094 patients with hypertensive kidney disease in the trial, this study tested whether the association between six previously identified risk factors for CKD progression (or death) and a composite clinical outcome (progression of CKD, ESRD, or death) depends on level of GFR. Multivariate Cox regression was used to control for other baseline risk factors.

Results: After controlling for baseline risk factors, only proteinuria was more closely associated with the composite clinical outcome at lower levels of GFR (P value for interaction term=0.002); increased hazards of the clinical composite outcome associated with a doubling of proteinuria ranged from 30% (95% confidence interval=21%-39%) with a GFR of 50 to 55% (95% confidence interval=40%-72%) with a GFR of 25.

Conclusions: The magnitude of the association between proteinuria and CKD progression, ESRD, or death in the African American Study of Kidney Disease Trial cohort depends on the level of GFR; proteinuria is a stronger independent predictor of the composite clinical outcome at lower levels of GFR. This finding reinforces that African Americans with proteinuria and lower GFR represent a population at particularly high risk for adverse outcomes.

Figure 1.

Kaplan–Meier survival curve stratified by GFR group and level of proteinuria. Proteinuria stratified by median level of protein/creatinine ratio (0.081). A trend to decreased survival (i.e., worse patient outcomes) caused by proteinuria in patients with lower GFR compared with patients with higher GFR is illustrated by a wider gap between solid lines (low GFR) compared with a smaller gap between dashed lines (high GFR). In an unadjusted Cox regression, the interaction between lower GFR and higher proteinuria strata was not statistically significant (P=0.16).

Figure 2.

Increased hazard of composite outcome associated with doubling of proteinuria stratified by GFR. Hazard ratios were obtained from estimated coefficients for proteinuria, GFR, and the interaction between proteinuria and GFR.