Pirfenidone for diabetic nephropathy

Kumar Sharma, Joachim H. Ix, Anna V. Mathew, Monique Cho, Axel Pflueger, Stephen R. Dunn, Barbara Francos, Shoba Sharma, Bonita Falkner, Tracy A. McGowan, Michael Donohue, Satish RamachandraRao, Ronghui Xu, Fernando C. Fervenza, Jeffrey B. Kopp

Research output: Contribution to journalArticle

169 Scopus citations

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 m 2). 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.

Original languageEnglish (US)
Pages (from-to)1144-1151
Number of pages8
JournalJournal of the American Society of Nephrology
Volume22
Issue number6
DOIs
StatePublished - Jun 1 2011

    Fingerprint

ASJC Scopus subject areas

  • Nephrology

Cite this

Sharma, K., Ix, J. H., Mathew, A. V., Cho, M., Pflueger, A., Dunn, S. R., Francos, B., Sharma, S., Falkner, B., McGowan, T. A., Donohue, M., RamachandraRao, S., Xu, R., Fervenza, F. C., & Kopp, J. B. (2011). Pirfenidone for diabetic nephropathy. Journal of the American Society of Nephrology, 22(6), 1144-1151. https://doi.org/10.1681/ASN.2010101049