Journal Article

Randomized trial of an intensified, multifactorial intervention in patients with advanced‐stage diabetic kidney disease: Diabetic Nephropathy Remission and Regression Team Trial in Japan (DNETT‐Japan)

Koya, Daisuke, Maeda, Shiro, Shikata, Kenichi, Akai, Hiroaki, Tomino, Yasuhiko, Makino, Hirofumi, Miyamoto, Satoshi, Haneda, Masakazu, Ogawa, Daisuke, Ninomiya, Toshiharu, Suzuki, Daisuke, Nishimura, Motonobu, Suzuki, Yoshiki, Uzu, Takashi, Ishida, Hitoshi

2021

Overview

Aims/Introduction We evaluated the efficacy of multifactorial intensive treatment (IT) on renal outcomes in patients with type 2 diabetes and advanced‐stage diabetic kidney disease (DKD). Materials and Methods The Diabetic Nephropathy Remission and Regression Team Trial in Japan (DNETT‐Japan) is a multicenter, open‐label, randomized controlled trial with a 5‐year follow‐up period. We randomly assigned 164 patients with advanced‐stage diabetic kidney disease (urinary albumin‐to‐creatinine ratio ≥300 mg/g creatinine, serum creatinine level 1.2–2.5 mg/dL in men and 1.0–2.5 mg/dL in women) to receive either IT or conventional treatment. The primary composite outcome was end‐stage kidney failure, doubling of serum creatinine or death from any cause, which was assessed in the intention‐to‐treat population. Results The IT tended to reduce the risk of primary end‐points as compared with conventional treatment, but the difference between treatment groups did not reach the statistically significant level (hazard ratio 0.69, 95% confidence interval 0.43–1.11; P = 0.13). Meanwhile, the decrease in serum low‐density lipoprotein cholesterol level and the use of statin were significantly associated with the decrease in primary outcome (hazard ratio 1.14; 95% confidence interval 1.05–1.23, P < 0.001 and hazard ratio 0.53, 95% confidence interval 0.28–0.998, P < 0.05, respectively). The incidence of adverse events was not different between treatment groups. Conclusions The risk of kidney events tended to decrease by IT, although it was not statistically significant. Lipid control using statin was associated with a lower risk of adverse kidney events. Further follow‐up study might show the effect of IT in patients with advanced diabetic kidney disease. The Diabetic Nephropathy Remission and Regression Team Trial in Japan was designed to clarify the beneficial effects of multifactorial intensified intervention by the team approach with medical staffs at each institution. There was an overall trend toward a lower risk on the development of kidney events in the intensive treatment group than in the conventional treatment group in this trial, but the benefit of intensive treatment could not be confirmed statistically. Lipid control by statin was associated with lower risk of kidney events in addition to strict control of blood glucose and blood pressure.

• Publisher: John Wiley & Sons, Inc,John Wiley and Sons Inc,Wiley
• Subject: Biomarkers - analysis / Blood Glucose - analysis / Blood pressure / Cholesterol / Clinical Trial / Clinical trials / Creatinine / Diabetes / Diabetes mellitus (non-insulin dependent) / Diabetes Mellitus, Type 2 - complications / Diabetic kidney disease / Diabetic Nephropathies - etiology / Diabetic Nephropathies - metabolism / Diabetic Nephropathies - pathology / Diabetic nephropathy / Diabetic Nephropathy Remission and Regression Team Trial in Japan / Diabetic retinopathy / Early Medical Intervention - methods / Female / Follow-Up Studies / Humans / Hypoglycemia / Independent study / Intervention / Kidney diseases / Laboratories / Low density lipoprotein / Male / Middle Aged / Nephropathy / Prognosis / Prospective Studies / Proteins / Remission / Remission (Medicine) / Remission Induction / Renal failure / Risk factors / Standard deviation / Statistical analysis / Vitamin deficiency / Vitamins