Protein kinase C β inhibition:: the promise for treatment of diabetic nephropathy

Purpose of review The prevalence of diabetes mellitus is increasing rapidly worldwide. The number of patients with diabetic nephropathy is also expected to increase considerably in the future despite currently available treatments that may prevent or slow kidney disease progression. Additional therapeutic agents are therefore urgently needed. Recent findings Ruboxistaurin mesylate is a bisinclolylmaleimicle that specifically inhibits the P-isoform of protein kinase C. In animal models of diabetic nephropathy, ruboxistaurin normalized glomerular hyperfiltration, decreased urinary albumin excretion, preserved renal function and reduced mesangial expansion, glomerulosclerosis, and tubulointerstitial fibrosis. In humans with type 2 diabetes and nephropathy already treated with an angiotensinconverting enzyme inhibitor or angiotensin receptor blocker, treatment with ruboxistaurin for 1 year reduced albuminuria and urinary transforming growth factor-P, and maintained estimated glomerular filtration rate. Ruboxistaurin has so far been shown to be well tolerated at the doses tested. Summary Inhibition of protein kinase C P may represent a novel strategy to improve kidney outcomes in patients with diabetes mellitus. Large-scale, prospective trials are needed to confirm the safety and potential benefits of ruboxistaurin in patients with diabetic nephropathy.