Received February 16, 2007
Accepted on April 24, 2007

ORIGINAL ARTICLES

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

Katherine R. Tuttle ^*1, Janet B. McGill , Douglas J. Haney , Toni E. Lin , Pamela W. Anderson , and 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

¹ To whom correspondence should be addressed. E-mail: ktuttle{at}this.org.

	Abstract

A pilot study showed that ruboxistaurin (RBX), a protein kinase C 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. 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. 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. 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.