Beraprost Sodium Protects Against Diabetic Nephropathy in Patients with Arteriosclerosis Obliterans: A Prospective, Randomized, Open-label Study.

BACKGROUND Inhibition of the renin-angiotensin system (RAS) has been used to treat diabetic nephropathy. However, RAS inhibition increases the risk of renal complications. In this study, we evaluated the effect of combining RAS inhibitor treatment with beraprost sodium (BPS), a prostaglandin I2 analog, in diabetic nephropathy with arteriosclerosis obliterans. METHODS This study was a prospective, randomized, open-label study. Twenty-six Japanese patients (age >30 years) with diabetic nephropathy and arteriosclerosis obliterans were randomly assigned to the BPS group (n=13), which received the combination of an RAS inhibitor and BPS (120 μg/day) therapy, or the control group (n=13), which received only an RAS inhibitor. Patients were followed up for 1 year. The primary endpoint was the effect of BPS on renal function. RESULTS In the control group, serum creatinine (1.64±0.87 to 2.34±1.53 mg/dL, p<0.001), 1/creatinine (0.82±0.47 to 0.65±0.47, p=0.003) cystatin C (1.77±0.61 to 2.18±0.86 mg/L, p<0.001), and the estimated glomerular filtration rate (43.9±26.1 to 34.0±24.6 mL/min/1.73 m(2), p=0.004) were significantly worsened 48 weeks after the start of treatment. Conversely, in the BPS group, serum creatinine (1.71±0.75 to 1.66±0.81 mg/dL, p=0.850), 1/creatinine (0.66±0.19 to 0.71±0.25, p=0.577), cystatin C (1.79±0.55 to 1.80±0.57 mg/L, p=0.999), and the estimated glomerular filtration rate (35.8±10.8 to 38.7±14.4 mL/min/1.73 m(2), p=0.613) were unchanged. CONCLUSIONS Combination treatment with BPS and an RAS inhibitor prevented the progression of diabetic nephropathy. These observations should be confirmed in large-scale studies with long-term follow-up.