Risk factors for renal replacement therapy in the Early Treatment Diabetic Retinopathy Study (ETDRS), Early Treatment Diabetic Retinopathy Study Report No. 26.

Background: Diabetes is a leading cause of end-stage renal disease (ESRD). The purpose of this study is to assess the risk factors for renal replacement therapy (RRT) in the Early Treatment Diabetic Retinopathy Study (ETDRS).

Methods: We examined demographic, clinical, and laboratory characteristics of the 2226 subjects with complete laboratory data enrolled in the ETDRS. The primary renal variable evaluated was the time to development of renal replacement therapy, defined as the need for dialysis or transplantation. Multivariable Cox proportional hazards regression was used to assess risk factors for type 1 and type 2 diabetes separately.

Results: The 5-year estimated incidence of RRT in the entire ETDRS population was 10.2% and 9.8% for patients with type 1 and type 2 diabetes, respectively. Of those patients with complete data, 127 of 934 (14%) of patients with type 1 diabetes, and 150 of 1292 (12%) patients with type 2 diabetes required RRT during the study. Baseline risk factors common to type 1 and type 2 diabetes included elevated total cholesterol, and serum creatinine; and low serum albumin and anemia. Other risk factors significant in type 1 diabetes included body mass index (BMI), shorter duration of diabetes, elevated hemoglobin A(1c) (HbA(1c)), elevated systolic blood pressure, and the development of proliferative diabetic retinopathy. Risk factors significant in type 2 diabetes, but not type 1 diabetes, included younger age, proteinuria, and elevated triglycerides.

Conclusion: In this study, major modifiable risk factors such as hypertension, dyslipidemia, and hyperglycemia were found to be predictive of RRT. Other predictors were markers of vascular pathology and inflammation, proteinuria, hypoalbuminemia, and increased serum creatinine. Controlled clinical trials with treatment strategies that improve serum lipid levels, systemic blood pressure, glycemic control, and markers of inflammation may be important in furthering our knowledge on the pathogenesis of diabetic complications such as nephropathy and ESRD.