Kidney Outcomes in Long-Term Studies of Ruboxistaurin for... : Clinical Journal of the American Society of Nephrology (original) (raw)

Diabetes and the Kidney

Kidney Outcomes in Long-Term Studies of Ruboxistaurin for Diabetic Eye Disease

Tuttle, Katherine R.; McGill, Janet B.; Haney, Douglas J.; Lin, Toni E.; Anderson, Pamela W. for the PKC-DRS, PKC-DMES, and PKC-DRS 2 Study Groups

*Providence Medical Research Center and University of Washington School of Medicine, Spokane, Washington; †Department of Medicine, Washington University, St. Louis, Missouri; and ‡Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana

Address correspondence to: Dr. Katherine R. Tuttle, 122 W. 7th Avenue, Suite 230, Spokane, WA 99204-2340. Phone: 509-474-4345; Fax: 509-474-4325; E-mail: [email protected]

Accepted April 24, 2007

Received February 16, 2007

Clinical Journal of the American Society of Nephrology 2(4):p 631-636, July 2007. | DOI: 10.2215/CJN.00840207

Abstract

Background: A pilot study showed that ruboxistaurin (RBX), a protein kinase C β inhibitor, significantly decreased albuminuria and stabilized kidney function over 1 yr in patients who had diabetic nephropathy and persistent macroalbuminuria despite receiving the current standard of care, including renin-angiotensin system inhibition. In contrast, in a trial of patients with diabetic retinopathy, investigators reported the adverse event “diabetic nephropathy” more frequently in patients who received RBX.

Design, setting, participants, and measurements: The purpose of this study was to evaluate long-term effects of RBX on kidney outcomes among patients with diabetic eye disease in three diabetic retinopathy trials (n = 1157). Baseline-to-study end changes in estimated GFR (eGFR) were calculated. Kidney outcomes included doubling of serum creatinine, development of advanced chronic kidney disease (stages 4 to 5), and death.

Results: Baseline eGFR was 81.6 ± 26.0 ml/min per 1.73 m2. In the combined placebo and RBX treatment groups, eGFR decreased by 11.0 ± 19.6 ml/min per 1.73 m2 during median follow-up of 33 to 39 mo. At least one kidney outcome occurred in 11.3% of patients. Frequency of doubling of serum creatinine was 6.0%, progression to advanced chronic kidney disease was 4.1%, and death was 4.1%. Kidney outcome rates did not differ by treatment assignment.

Conclusions: Long-term kidney outcomes in patients with diabetic eye disease were similar in placebo and RBX groups. In conclusion, large-scale, prospective trials in patients with diabetic nephropathy are needed to confirm safety and potential benefits of RBX on clinical outcomes.