title: Pirfenidone for diabetic nephropathy.
abstract: Pirfenidone is an oral antifibrotic agent that benefits diabetic nephropathy in animal models, but whether it is effective for human diabetic nephropathy is unknown. We conducted a randomized, double-blind, placebo-controlled study in 77 subjects with diabetic nephropathy who had elevated albuminuria and reduced estimated GFR (eGFR) (20 to 75 ml/min per 1.73 m²). The prespecified primary outcome was a change in eGFR after 1 year of therapy. We randomly assigned 26 subjects to placebo, 26 to pirfenidone at 1200 mg/d, and 25 to pirfenidone at 2400 mg/d. Among the 52 subjects who completed the study, the mean eGFR increased in the pirfenidone 1200-mg/d group (+3.3 ± 8.5 ml/min per 1.73 m²) whereas the mean eGFR decreased in the placebo group (-2.2 ± 4.8 ml/min per 1.73 m²; P = 0.026 versus pirfenidone at 1200 mg/d). The dropout rate was high (11 of 25) in the pirfenidone 2400-mg/d group, and the change in eGFR was not significantly different from placebo (-1.9 ± 6.7 ml/min per 1.73 m²). Of the 77 subjects, 4 initiated hemodialysis in the placebo group, 1 in the pirfenidone 2400-mg/d group, and none in the pirfenidone 1200-mg/d group during the study (P = 0.25). Baseline levels of plasma biomarkers of inflammation and fibrosis significantly correlated with baseline eGFR but did not predict response to therapy. In conclusion, these results suggest that pirfenidone is a promising agent for individuals with overt diabetic nephropathy.
authors.affiliation: Center for Renal Translational Medicine, University of California-San Diego/Veteran Affairs Medical Center, La Jolla, CA 92093-0711, USA. kumarsharma@ucsd.edu
authors.forename: Kumar
authors.initials: K
authors.lastname: Sharma
authors.forename: Joachim H
authors.initials: JH
authors.lastname: Ix
authors.forename: Anna V
authors.initials: AV
authors.lastname: Mathew
authors.forename: Monique
authors.initials: M
authors.lastname: Cho
authors.forename: Axel
authors.initials: A
authors.lastname: Pflueger
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Dunn
authors.forename: Barbara
authors.initials: B
authors.lastname: Francos
authors.forename: Shoba
authors.initials: S
authors.lastname: Sharma
authors.forename: Bonita
authors.initials: B
authors.lastname: Falkner
authors.forename: Tracy A
authors.initials: TA
authors.lastname: McGowan
authors.forename: Michael
authors.initials: M
authors.lastname: Donohue
authors.forename: Satish
authors.initials: S
authors.lastname: Ramachandrarao
authors.forename: Ronghui
authors.initials: R
authors.lastname: Xu
authors.forename: Fernando C
authors.initials: FC
authors.lastname: Fervenza
authors.forename: Jeffrey B
authors.initials: JB
authors.lastname: Kopp
mesh_terms: D000328:Adult; D000368:Aged; D000419:Albuminuria / Q000652:urine; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use*; D015415:Biomarkers / Q000652:urine; D003404:Creatinine / Q000652:urine; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology*; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005355:Fibrosis; D005919:Glomerular Filtration Rate / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007668:Kidney / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011728:Pyridones / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D015415:Biomarkers; D011728:Pyridones; D003404:Creatinine; C093844:pirfenidone