Pirfenidone for Diabetic Nephropathy

• Published in: Journal of the American Society of Nephrology Vol. 22; no. 6; pp. 1144 - 1151
• Main Authors: Sharma, Kumar, Ix, Joachim H., Mathew, Anna V., Cho, Monique, Pflueger, Axel, Dunn, Stephen R., Francos, Barbara, Sharma, Shoba, Falkner, Bonita, McGowan, Tracy A., Donohue, Michael, RamachandraRao, Satish, Xu, Ronghui, Fervenza, Fernando C., Kopp, Jeffrey B.
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society of Nephrology 01.06.2011
• Subjects: Adult; Aged; Albuminuria - urine; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Anti-Inflammatory Agents, Non-Steroidal - therapeutic use; Associated diseases and complications; Biological and medical sciences; Biomarkers - urine; Clinical Research; Creatinine - urine; Diabetes. Impaired glucose tolerance; Diabetic Nephropathies - drug therapy; Diabetic Nephropathies - metabolism; Diabetic Nephropathies - physiopathology; Disease Progression; Dose-Response Relationship, Drug; Double-Blind Method; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Female; Fibrosis; Glomerular Filtration Rate - drug effects; Glomerular Filtration Rate - physiology; Humans; Kidney - pathology; Kidneys; Male; Medical sciences; Middle Aged; Nephrology. Urinary tract diseases; Pyridones - pharmacology; Pyridones - therapeutic use; Treatment Outcome; Urinary system involvement in other diseases. Miscellaneous; Endocrinopathy; Kidney disease; Concomitant disease; Nephrology; Urinary system disease; Diabetes mellitus; Diabetic nephropathy; Pirfenidone; Urology
• ISSN: 1046-6673; 1533-3450; 1533-3450
• DOI: 10.1681/ASN.2010101049

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.