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CLINICAL RESEARCH

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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, and Jeffrey B. Kopp§

*Center for Renal Translational Medicine, Department of Medicine, University of California–San Diego/Veteran

Affairs San Diego Healthcare System, La Jolla, California; †Division of Nephrology and ‡Clinical and Translational

Research Institute, University of California–San Diego, San Diego, California; §Mayo Clinic, Rochester, Minnesota;

Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of

Health, Bethesda, Maryland; ¶Kimmel Cancer Center and **Department of Medicine, Thomas Jefferson University,

Philadelphia, Pennsylvania; and ††Johnson and Johnson, Inc., Horsham, Pennsylvania

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, placebocontrolled 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...