• % change in urine albumin excretion from baseline to end of study period. [ Time Frame: 12 months ] [ Designated as safety issue: No ]
• % change in levels of TGF-b1 in urine, plasma and serum from baseline to end of study period. [ Time Frame: 12 months ] [ Designated as safety issue: No ]
• • Determine the relationship between % change in TGF-b1 levels and the change in GFR [ Time Frame: 12 months ] [ Designated as safety issue: No ]

The purpose of this study is to determine whether a new investigational drug, pirfenidone, will be an effective therapy for diabetic patients with kidney dysfunction. Our hypothesis is that administration of pirfenidone to type 1 and type 2 diabetic patients with advanced kidney disease will lead to preservation of kidney function.

Diabetic kidney disease is the leading cause of new cases of kidney failure in the United States. In the kidneys of diabetic patients, there is accumulation of protein that leads to the formation of scar tissue and poor kidney function. Because of this many patients eventually require dialysis or kidney transplantation. A new investigational drug, pirfenidone, has been shown to be beneficial in a number of diseases in which scar formation leads to disease progression. It is our goal to examine whether pirfenidone is effective at stabilizing or reducing progressive diabetic kidney dysfunction.

• Diabetes Mellitus
• Diabetic Nephropathy

• Placebo Comparator: Placebo
• Experimental: Pirfenidone will be administered at a dose of 1200 mg/day
• Experimental: Pirfenidone will be administered at 2400 mg/day

• Sharma K, Ziyadeh FN, Alzahabi B, McGowan TA, Kapoor S, Kurnik BR, Kurnik PB, Weisberg LS. Increased renal production of transforming growth factor-beta1 in patients with type II diabetes. Diabetes. 1997 May;46(5):854-9.
• Shimizu T, Fukagawa M, Kuroda T, Hata S, Iwasaki Y, Nemoto M, Shirai K, Yamauchi S, Margolin SB, Shimizu F, Kurokawa K. Pirfenidone prevents collagen accumulation in the remnant kidney in rats with partial nephrectomy. Kidney Int Suppl. 1997 Dec;63:S239-43.
• Iyer SN, Gurujeyalakshmi G, Giri SN. Effects of pirfenidone on transforming growth factor-beta gene expression at the transcriptional level in bleomycin hamster model of lung fibrosis. J Pharmacol Exp Ther. 1999 Oct;291(1):367-73.
• Raghu G, Johnson WC, Lockhart D, Mageto Y. Treatment of idiopathic pulmonary fibrosis with a new antifibrotic agent, pirfenidone: results of a prospective, open-label Phase II study. Am J Respir Crit Care Med. 1999 Apr;159(4 Pt 1):1061-9.

Inclusion

• Type 1 or type 2 diabetes
• Males and females greater than or equal to 18 years.
• Abnormal kidney function determined by glomerular filtration rate
• History of proteinuria
• Blood pressure controlled to <140/90 on anti-hypertensive medication

Exclusion

• Cancer, liver disease, hepatitis, HIV+
• History of heart attack, unstable angina, stroke or peptic ulcer in the past 6 months
• Pregnant or planning to become pregnant during the study period
• Other known kidney disease besides diabetic nephropathy
• Expect to begin dialysis or receive a kidney transplant within 1 year of study enrollment

• National Institutes of Health (NIH)
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)