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<60mL/min/1.73m2. After 12weeks of atrasentan treatment in patients with eGFR<60mL/min/1.73m2, 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 1.25mg/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 1.25mg/d, respectively. These data corroborate previous findings of mitochondrial dysfunction in patients with type 2 diabetes, nephropathy and eGFR<60mL/min/1.73m2, 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.
- Diabetic kidney disease
- eGFR decline
ASJC Scopus subject areas
- Internal Medicine
- Endocrinology, Diabetes and Metabolism