02335nas a2200313   4500000000100000008004100001100002100042700002000063700001700083700001800100700001900118700001700137700001600154700001800170700001900188700001700207700002600224700001400250700001700264700002000281700002400301700001700325700001900342245010300361300001200464490000700476520152400483022001402007       2017                            d1 aRemuzzi Giuseppe1 aHeerspink Hiddo1 aTobe Sheldon1 ade Zeeuw Dick1 aPerkovic Vlado1 aSharma Kumar1 aToto Robert1 aPena Michelle1 aAndress Dennis1 aBrennan John1 aCorrea-Rotter Ricardo1 aColl Blai1 aKohan Donald1 aMakino Hirofumi1 aParving Hans-Henrik1 aSharma Shoba1 aCorringham Tom00aThe effects of atrasentan on urinary metabolites in patients with type 2 diabetes and nephropathy.  a749-7530 v193 a<p>
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 &lt; 60 mL/min/1.73 m(2) . After 12 weeks of atrasentan treatment in patients with eGFR &lt; 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 &lt; 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.
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