A Non-purine Xanthine Oxidoreductase Inhibitor Reduces Albuminuria in Patients with DKD: A Randomized Controlled Trial.

Autor:	Bakris GL; Medicine, The University of Chicago, Chicago, Illinois., Mikami H; Teijin America, Inc., New York, New York., Hirata M; Teijin America, Inc., New York, New York., Nakajima A; Pharmaceutical Development Administration Department, Teijin Pharma Limited, Tokyo, Japan., Cressman MD; Cardiovascular, Metabolic, Endocrine and Renal, Labcorp Drug Development, Inc., Princeton, New Jersey.
Jazyk:	angličtina
Zdroj:	Kidney360 [Kidney360] 2021 Jun 30; Vol. 2 (8), pp. 1240-1250. Date of Electronic Publication: 2021 Jun 30 (Print Publication: 2021).
DOI:	10.34067/KID.0001672021
Abstrakt:	Background: Diabetic kidney disease (DKD) is characterized by albuminuria and reduced renal function. Whether xanthine oxidoreductase inhibitors (XORIs) have a renoprotective effect in DKD patients with type 2 diabetes remains controversial. We conducted a proof-of-concept study to investigate the renal effects of a novel XORI, TMX-049, in patients with DKD and type 2 diabetes. Methods: This is a multicenter, 12-week, randomized, double-blind, placebo-controlled phase 2a trial conducted at 49 centers across the United States between April 2018 and June 2019. In total, 130 patients with type 2 diabetes, urine albumin-creatinine ratio (UACR) 200 - 3000 mg/g, eGFR ≥30 ml/min per 1.73 m 2 , and serum uric acid (sUA) 4 - 10 mg/dl were randomized 1:1:1 to TMX-049 200 mg ( n =44) or 40 mg ( n =44), or placebo ( n =42). The primary end point was change in log-transformed UACR at week 12 from baseline. The secondary end points included changes in UACR, eGFR, and sUA from baseline. Results: The least squares mean differences for changes in log-transformed UACR from baseline to week 12 compared with placebo were -0.43 (95% confidence interval [95% CI], -0.82 to -0.04, P =0.03) for TMX-049 200 mg and -0.05 (95% CI, -0.44 to 0.34, P =0.80) for 40 mg; a 35% reduction in UACR was observed with TMX-049 200 mg (ratio versus placebo, 0.65; 95% CI, 0.44 to 0.96) but not 40 mg (0.95; 95% CI, 0.64 to 1.41). Throughout the treatment period, marked reductions in sUA levels but no changes in eGFR were observed with both TMX-049 doses. TMX-049 was generally well tolerated, although two patients with TMX-049 200 mg developed gout. Conclusions: TMX-049 200 mg reduced albuminuria at 12 weeks in patients with DKD and type 2 diabetes. TMX-049 may exert a renoprotective effect independent of its sUA-lowering effect. Competing Interests: A. Nakajima. H. Mikami, and M. Hirata are employees of Teijin and hold Teijin stocks. G.L. Bakris reports receiving fees from Teijin for his consultation of this study and from Alynium, KBP Bioscience, Ionis, Merck, and Relypsa for consultations outside of the submitted work; and reports serving as a member of the steering committee of international outcome trials; and reports his institution received fees from Bayer, Novo Nordisk, and Vascular Dynamics. M.D. Cressman was an employee of Covance when this trial was conducted, and received fees from Teijin for this publication. (Copyright © 2021 by the American Society of Nephrology.)
Databáze:	MEDLINE
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