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The effects of atrasentan on urinary metabolites in patients with type 2 diabetes and nephropathy.
- Source :
-
Diabetes, obesity & metabolism [Diabetes Obes Metab] 2017 May; Vol. 19 (5), pp. 749-753. Date of Electronic Publication: 2017 Feb 22. - Publication Year :
- 2017
-
Abstract
- 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 <superscript>2</superscript> . After 12 weeks of atrasentan treatment in patients with eGFR < 60 mL/min/1.73 m <superscript>2</superscript> , 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 <superscript>2</superscript> , 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.<br /> (© 2016 John Wiley & Sons Ltd.)
- Subjects :
- Albuminuria etiology
Albuminuria prevention & control
Atrasentan
Biomarkers urine
Canada
Diabetic Nephropathies metabolism
Diabetic Nephropathies physiopathology
Diabetic Nephropathies urine
Disease Progression
Dose-Response Relationship, Drug
Double-Blind Method
Endothelin Receptor Antagonists administration & dosage
Endothelin Receptor Antagonists adverse effects
Follow-Up Studies
Gas Chromatography-Mass Spectrometry
Glomerular Filtration Rate
Humans
Kidney metabolism
Mitochondria metabolism
Pyrrolidines administration & dosage
Pyrrolidines adverse effects
Renal Insufficiency complications
Renal Insufficiency metabolism
Renal Insufficiency physiopathology
Reproducibility of Results
Taiwan
United States
Diabetes Mellitus, Type 2 complications
Diabetic Nephropathies drug therapy
Endothelin Receptor Antagonists therapeutic use
Kidney drug effects
Mitochondria drug effects
Pyrrolidines therapeutic use
Renal Insufficiency drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1463-1326
- Volume :
- 19
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Diabetes, obesity & metabolism
- Publication Type :
- Academic Journal
- Accession number :
- 28019071
- Full Text :
- https://doi.org/10.1111/dom.12864