Intensified multifactorial intervention leads to long‐term benefit on kidney outcomes in advanced diabetic kidney disease: A 10‐year follow‐up of the DNETT ‐Japan trial

Introduction Despite recent therapeutic advances in slowing kidney disease progression, the long‐term efficacy of intensive multifactorial treatment in advanced‐stage diabetic kidney disease remains unclear. We assessed long‐term kidney outcomes through the 5‐year Diabetic Nephropathy Remission and Regression Team Trial in Japan (DNETT‐Japan) and an additional 5‐year post‐trial observational follow‐up. Materials and Methods A total of 164 patients with advanced‐stage diabetic kidney disease (urinary albumin‐to‐creatinine ratio ≥ 300 mg/g and serum creatinine 1.2–2.5 mg/dL in men and 1.0–2.5 mg/dL in women) were randomly assigned to intensive multifactorial treatment—targeting glycemic, blood pressure, and lipid control with lifestyle modification—or conventional treatment for 5 years. After the intervention, an additional 5‐year observational follow‐up was conducted. The primary outcome was the composite of a doubling of serum creatinine, end‐stage kidney disease, or all‐cause death. Results Forty‐four patients who were free of the primary outcome during the intervention entered the follow‐up study. The risk of the primary outcome was lower in the intensive multifactorial treatment group versus the conventional treatment group (hazard ratio, 0.62; 95% confidence interval, 0.41–0.93; P = 0.021). Increases in systolic blood pressure (per 10 mmHg) and serum low‐density lipoprotein cholesterol (per 10 mg/dL) during the intervention were associated with a higher risk of the primary outcome (hazard ratio, 1.43 [1.15–1.78] and 1.23 [1.12–1.35], respectively). Discussion The benefit of 5‐year intensive multifactorial treatment on kidney outcomes was demonstrated during an additional 5‐year follow‐up period, highlighting the importance of sustained comprehensive risk‐factor management in advanced‐stage diabetic kidney disease.