Abstract
BACKGROUND: According to studies by the National Kidney Foundation and Food and Drug Administration, 30% and 40% declines in estimated glomerular filtration rate (eGFR) could be used as surrogate endpoints of end-stage renal disease (ESRD). However, the benefits of using these endpoints in diabetic patients remain unclear. METHODS: This cohort study comprised Japanese patients with type 2 diabetes; those with repeated serum creatinine measurements during a baseline period of 2 years (n = 1868) or 3 years (n = 2001) were enrolled. Subsequent risks of ESRD following eGFR declines were assessed. RESULTS: In the 2-year baseline analysis, the cumulative prevalence of -20%, -30%, -40%, and -53% changes in eGFR were 23.9%, 11.1%, 6.8%, and 3.7%, respectively. There were 133 cases (7.1%) of subsequent ESRD during a median follow-up period of 6.5 years. In the 3-year baseline analysis, the corresponding proportions were 28.1%, 14.0%, 7.7%, and 3.9%, respectively, with 110 participants (5.5%) reaching ESRD during a median follow-up period of 5.5 years. The adjusted hazard ratios of subsequent ESRD following -53%, -40%, -30%, and -20% changes in eGFR during the 2-year baseline period were 22.9 (11.1-47.3), 12.8 (6.9-23.7), 8.2 (4.3-15.5), and 3.9 (2.2-7.0), respectively when compared with the no changes in eGFR. In the 3-year baseline analysis, the corresponding risks were 29.7 (10.8-81.9), 18.4 (7.6-44.7), 12.8 (5.2-32.2), and 5.4 (2.3-12.8), respectively. In the subgroup analysis, similar trends were observed in patients with macroalbuminuria at baseline. CONCLUSIONS: Declines in eGFR were strongly associated with subsequent risk of ESRD in Japanese type 2 diabetic patients. In addition to 30% and 40% declines, a 20% decline in eGFR over 2 years could be considered as a candidate surrogate endpoint of ESRD in diabetic kidney disease.