Kidney outcomes in long-term studies of ruboxistaurin for diabetic eye disease.
BACKGROUND
A pilot study showed that ruboxistaurin (RBX), a protein kinase C beta 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.


METHODS
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 m(2). In the combined placebo and RBX treatment groups, eGFR decreased by 11.0 +/- 19.6 ml/min per 1.73 m(2) 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.
Tuttle
Katherine R
KR
Providence Medical Research Center and University of Washington School of Medicine, Spokane, Washington, USA. ktuttle@this.org
McGill
Janet B
JB
Haney
Douglas J
DJ
Lin
Toni E
TE
Anderson
Pamela W
PW
D003928:Diabetic Nephropathies / Q000150:complications / Q000188:drug therapy; D003930:Diabetic Retinopathy / Q000150:complications / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects* / Q000502:physiology*; D008297:Male; D008301:Maleimides / Q000627:therapeutic use*; D008875:Middle Aged; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D013997:Time Factors
D007211:Indoles; D008301:Maleimides; C099154:ruboxistaurin; D011493:Protein Kinase C