Recent research, which appears in the current issue of Diabetes Care, establishes Ruboxistaurin as a promising novel treatment that may improve upon established therapies for diabetic nephropathy.
Nephropathy is known to develop in 40% of people with type 2 diabetes and is the leading cause of end-stage renal disease in the U.S. and the developed world.
Many persons with diabetes have progressive nephropathy even with the established therapies. Therefore, treatments targeting novel pathogenic mechanisms may be beneficial.
Studies have shown an important role for protein kinase C (PKC)-ß in the pathogenesis of diabetic nephropathy. Ruboxistaurin selectively inhibits protein kinase C-ß and ameliorates kidney disease in animal models of diabetes.
The study was performed to evaluate the effects of 32mg/day ruboxistaurin for 1 year in persons with type 2 diabetes and persistent albuminuria persistent albuminuria (albumin-to-creatinine ratio [ACR] 200-2,000 mg/g), despite therapy with renin-angiotensin system inhibitors. The primary end point was a change in the ACR. Estimated glomerular filtration rate (eGFR) was also calculated.
It was found that after one year, urinary ACR decreased significantly in participants treated with ruboxistaurin and nonsignificantly in the placebo group. The ACR-lowering effect of ruboxistaurin appeared by 1 month. eGFR did not decline significantly in the ruboxistaurin group, whereas the placebo group lost significant eGFR over 1 year.
Between-group differences for changes in ACR and eGFR were not statistically significant, but this pilot study was underpowered to determine such differences.
The study authors conclude that ruboxistaurin had favorable effects on albuminuria and renal function in persons with type 2 diabetes and nephropathy. The albuminuria-lowering effect occurred early and was sustained long term. Those treated with ruboxistaurin did not experience a significant decline in renal function. Ruboxistaurin may thus add benefit to established therapies for diabetic nephropathy.
The authors suggest that large-scale trials should be performed to confirm its effectiveness and safety.