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Randomized Controlled Trial
. 2021 Feb;12(2):207-216.
doi: 10.1111/jdi.13339. Epub 2020 Aug 8.

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)

Kenichi Shikata  1 , Masakazu Haneda  2 , Toshiharu Ninomiya  3 , Daisuke Koya  4 , Yoshiki Suzuki  5 , Daisuke Suzuki  6 , Hitoshi Ishida  7 , Hiroaki Akai  8 , Yasuhiko Tomino  9 , Takashi Uzu  10 , Motonobu Nishimura  11 , Shiro Maeda  12   13 , Daisuke Ogawa  14 , Satoshi Miyamoto  1 , Hirofumi Makino  15 ; Diabetic Nephropathy Remission and Regression Team Trial in Japan (DNETT-Japan) collaborative group
Affiliations
Randomized Controlled Trial

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)

Kenichi Shikata et al. J Diabetes Investig. 2021 Feb.

Abstract

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.

Keywords: Diabetic Nephropathy Remission and Regression Team Trial in Japan; Diabetic kidney disease; Diabetic nephropathy.

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Conflict of interest statement

KS received speaker fees from MSD, Eli Lilly Japan, Nippon Boehringer Ingelheim, Novo Nordisk Pharma, Mitsubishi Tanabe and Kyowa Hakko Kirin; research support from Takeda, MSD, Kyowa Hakko Kirin and Mitsubishi Tanabe; and a consulting fee from Daiichi Sankyo. MH has received speaker fees from Astellas, Taisho‐Toyama, Tanabe‐Mitsubishi, Boehringer Ingelheim, Taisho, Kowa, Ono, MSD, Novartis and Novo‐Nordisk; and research support from Novo‐Nordisk, Ono, Shionogi and Johnson & Johnson. DK received speaker fees from MSD, Astellas Pharma Inc., Ono, Taisho, Mitsubishi Tanabe, Eli Lilly Japan, Boehringer‐Ingelheim Japan and Novo Nordisk Pharma; and research support from Ono., Taisho, Mitsubishi Tanabe and Boehringer‐Ingelheim Japan. HA received a research grant from Ono and Boehringer Ingelheim GmbH. MN received speaker fees from Mitsubishi Tanabe, Takeda, Kyowa Kirin, Taisho, Novo Nordisk Pharma and Daiichi Sankyo. HM is a consultant for AbbVie, Teijin and Boehringer‐Ingelheim Japan. TN, YS, SM, DS, TY, TU, DO and SM declare no conflict of interest.

Figures

Figure 1
Figure 1
Trial profile.
Figure 2
Figure 2
Event‐free survival of primary outcomes (dialysis, doubling of serum creatinine or death) in the randomized patients (full analysis set). The effects of treatment (hazard ratios with 95% confidence intervals, and P‐values) were estimated by using a Cox proportional hazards model. CI, confidence interval; HR, hazard ratio.
Figure 3
Figure 3
Effects of trial treatment on each outcome in the randomized patients. The effects of treatment (hazard ratios with 95% confidence intervals and P ‐values) were estimated by using a Cox proportional hazards model. CI, confidence interval; HR, hazard ratio.
See this image and copyright information in PMC

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