Probucol suppresses initiation of chronic hemodialysis therapy and renal dysfunction-related death in diabetic nephropathy patients: Sakura study.

Aim: Probucol has antioxidant as well as cholesterol-lowering effects. We examined the effect of probucol on the progression of diabetic nephropathy. We named this study 'Sakura Study' after our hospital and city. Methods: We performed a randomized, open trial on 162 type 2 diabetic patients with clinical albuminuria (urinary albumin excretion > 300 mg/g creatinine). Eighty patients were assigned to probucol treatment (500 mg/day) and 82 patients to no probucol treatment. All patients were followed for five years. The primary outcome was the time to renal dysfunction events, defined as the initiation of chronic hemodialysis therapy and renal dysfunction-related death. Results: Probucol decreased total cholesterol, HDL-cholesterol, and LDL-cholesterol compared to the control group. The serum creatinine increase rate was significantly lower (p=0.015) in the probucol group (0.066 mg/dL/month) than in the non-probucol group (0.116 mg/dL/month). Renal dysfunction events occurred in 72 patients during this study. The 69 patients who were initiated on chronic hemodialysis comprised 42 in the non-probucol group and 27 in the probucol group. Three patients in the non-probucol group, but no patients in the probucol group died of renal dysfunction. The renal dysfunction event-free survival rate was significantly higher (log-rank: p=0.02) in the probucol group than in the non-probucol group. Conclusion: Probucol suppressed the progression of diabetic nephropathy and renal dysfunction events.