Albuminuria and estimated glomerular filtration rate as predictors of diabetic end-stage renal disease and death

Abstract

Background and objectives: We investigated predictive value of albuminuria and estimated GFR (eGFR) for ESRD in Pima Indians with type 2 diabetes.

Design, setting, participants and measurements: Beginning in 1982, 2420 diabetic Pima Indians ≥18 years old were followed until they developed ESRD or died or until December 31, 2005. Individuals were classified at baseline by urinary albumin-to-creatinine ratio (ACR) and by eGFR, calculated by the Chronic Kidney Disease Epidemiology Collaboration equation. Predictors of ESRD and mortality were examined by proportional hazards regression.

Results: During a mean follow-up of 10.2 years, 287 individuals developed ESRD. Incidence of ESRD among individuals with macroalbuminuria (ACR ≥ 300 mg/g) was 9.3 times that of those with normoalbuminuria (ACR < 30 mg/g), controlled for age, gender, and duration of diabetes. Incidence among individuals with eGFR 15 to 29 ml/min per 1.73 m(2) was 81.9 times that of those with eGFR 90 to 119 ml/min per 1.73 m(2). Models that combined albuminuria and eGFR added significant predictive information about risk of ESRD or death compared with models containing eGFR or albuminuria alone. The hazard ratio for ESRD associated with a 10-ml/min per 1.73 m(2) lower eGFR was 1.36, whereas that associated with an increase in albuminuria category was 2.69; corresponding hazard ratios for death were 1.15 and 1.37.

Conclusions: These results suggest that incorporation of quantitative information about albuminuria into staging systems based on eGFR adds significant prognostic information about risk for diabetic ESRD and death.

Figure 1.

(A) Hazard ratio of ESRD, adjusted for age, gender, and duration of diabetes and categorized by albuminuria and estimated GFR (eGFR) in Pima Indians with type 2 diabetes mellitus (T2DM). [n=2420, 287 of whom developed diabetic ESRD] Individuals with normoalbuminuria and eGFR 90 to 119 ml/min per 1.73 m² were the referent group m. The hazard ratios (95% confidence intervals) compared with the referent group are 1.2 (0.8 to 2.0) for normoalbuminuria and eGFR ≥ 120 ml/min per 1.73 m², 1.5 (0.6 to 4.0) for normoalbuminuria and eGFR 60 to 89 ml/min per 1.73 m², 5.7 (0.8 to 42.1) for normoalbuminuria and eGFR 30 to 59 ml/min per 1.73 m², 1.3 (0.7 to 2.4) for microalbuminuria and eGFR ≥ 120 ml/min per 1.73 m², 3.1 (2.0 to 4.8) for microalbuminuria and eGFR 90 to 119 ml/min per 1.73 m², 6.0 (3.0 to 11.0) for microalbuminuria and eGFR 60 to 89 ml/min per 1.73 m², 3.8 (0.5 to 28.1) for microalbuminuria and eGFR 30 to 59 ml/min per 1.73 m², 6.9 (3.6 to 13.1) for macroalbuminuria and eGFR ≥ 120 ml/min per 1.73 m², 8.7 (5.6 to 13.6) for macroalbuminuria and eGFR 90 to 119 ml/min per 1.73 m², 14.6 (8.7 to 24.4) for macroalbuminuria and eGFR 60 to 89 ml/min per 1.73 m², 56.6 (31.8 to 100.7) for macroalbuminuria and eGFR 30 to 59 ml/min per 1.73 m², and 290.9 (130.0 to 650.8) for macroalbuminuria and eGFR 15 to 29 ml/min per 1.73 m². (B) Cumulative incidence of ESRD at 10-year follow-up for categories of albuminuria and eGFR. Cumulative incidence is calculated from the proportional hazards model and the baseline hazard rate, adjusted for age, gender, and duration of diabetes. (C) Hazard ratio of mortality adjusted for age, gender, and duration of diabetes and categorized by albuminuria and eGFR in Pima Indians with T2DM [n=2420, 570 of whom died during follow-up]. Individuals with normoalbuminuria and eGFR 90 to 119 ml/min per 1.73 m² were the referent group m. The hazard ratios (95% confidence intervals) compared with the referent group are 1.2 (0.9 to 1.7) for normoalbuminuria and eGFR ≥ 120 ml/min per 1.73 m², 1.6 (1.1 to 2.3) for normoalbuminuria and eGFR 60 to 89 ml/min per 1.73 m², 2.3 (0.8 to 6.1) for normoalbuminuria and eGFR 30 to 59 ml/min per 1.73 m², 1.0 (0.6 to 1.7) for microalbuminuria and eGFR ≥ 120 ml/min per 1.73 m², 1.5 (1.1 to 1.9) for microalbuminuria and eGFR 90 to 119 ml/min per 1.73 m², 2.0 (1.3 to 3.0) for microalbuminuria and eGFR 60 to 89 ml/min per 1.73 m², 4.3 (2.1 to 8.9) for microalbuminuria and eGFR 30 to 59 ml/min per 1.73 m², 2.9 (1.7 to 5.1) for macroalbuminuria and eGFR ≥ 120 ml/min per 1.73 m², 2.0 (1.4 to 2.7) for macroalbuminuria and eGFR 90 to 119 ml/min per 1.73 m², 2.5 (1.8 to 3.6) for macroalbuminuria and eGFR 60 to 89 ml/min per 1.73 m², 6.5 (4.4 to 9.8) for macroalbuminuria and eGFR 30 to 59 ml/min per 1.73 m², and 7.5 (4.2 to 13.5) for macroalbuminuria and eGFR 15 to 29 ml/min per 1.73 m². (D) Cumulative mortality at 10-year follow-up for categories of albuminuria and eGFR. Cumulative mortality is calculated from the proportional hazards model and the baseline hazard rate, adjusted for age, gender, and duration of diabetes.