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The effects of atrasentan on urinary metabolites in patients with type 2 diabetes and nephropathy
Author(s) -
Pena Michelle J.,
de Zeeuw Dick,
Andress Dennis,
Brennan John J.,
CorreaRotter Ricardo,
Coll Blai,
Kohan Donald E.,
Makino Hirofumi,
Perkovic Vlado,
Remuzzi Giuseppe,
Tobe Sheldon W.,
Toto Robert,
Parving HansHenrik,
Sharma Shoba,
Corringham Tom,
Sharma Kumar,
Heerspink Hiddo J. L.
Publication year - 2017
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/dom.12864
Subject(s) - urology , albuminuria , medicine , type 2 diabetes , placebo , diabetic nephropathy , metabolite , diabetes mellitus , urine , population , urinary system , renal function , endocrinology , gastroenterology , pathology , alternative medicine , environmental health
We assessed the effect of atrasentan therapy on a pre‐specified panel of 13 urinary metabolites known to reflect mitochondrial function in patients with diabetic kidney disease. This post‐hoc analysis was performed using urine samples collected during the RADAR study which was a randomized, double‐blind, placebo‐controlled trial that tested the effects of atrasentan on albuminuria reduction in patients with type 2 diabetes and nephropathy. At baseline, 4 of the 13 metabolites, quantified by gas‐chromatography mass spectrometry, were below detectable levels, and 6 were reduced in patients with eGFR < 60 mL/min/1.73 m 2 . After 12 weeks of atrasentan treatment in patients with eGFR < 60 mL/min/1.73 m 2 , a single‐value index of the metabolites changed by −0.31 (95%CI −0.60 to −0.02; P = .035), −0.08 (−12 to 0.29; P = .43) and 0.01 (−0.21 to 0.19; P = .913) in placebo, atrasentan 0.75 and 1.25 mg/d, respectively. The metabolite index difference compared to placebo was 0.13 (−0.17 to 0.43; P = .40) and 0.35 (0.05‐0.65; P = .02) for atrasentan 0.75 and 1.25 mg/d, respectively. These data corroborate previous findings of mitochondrial dysfunction in patients with type 2 diabetes, nephropathy and eGFR < 60 mL/min/1.73 m 2 , suggesting that atrasentan may prevent the progression of mitochondrial dysfunction common to this specific patient population. Future studies of longer treatment duration with atrasentan are indicated.