TY - JOUR
T1 - Protein kinase C β inhibition
T2 - The promise for treatment of diabetic nephropathy
AU - Anderson, Pamela W.
AU - McGill, Janet B.
AU - Tuttle, Katherine R.
PY - 2007/9
Y1 - 2007/9
N2 - 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 bisindolylmaleimide that specifically inhibits the β-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 angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, treatment with ruboxistaurin for 1 year reduced albuminuria and urinary transforming growth factor-β, 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 β 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.
AB - 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 bisindolylmaleimide that specifically inhibits the β-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 angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, treatment with ruboxistaurin for 1 year reduced albuminuria and urinary transforming growth factor-β, 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 β 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.
KW - Diabetic nephropathy
KW - Protein kinase C β
UR - http://www.scopus.com/inward/record.url?scp=34547922467&partnerID=8YFLogxK
U2 - 10.1097/MNH.0b013e3281ead025
DO - 10.1097/MNH.0b013e3281ead025
M3 - Review article
C2 - 17693752
AN - SCOPUS:34547922467
SN - 1062-4821
VL - 16
SP - 397
EP - 402
JO - Current Opinion in Nephrology and Hypertension
JF - Current Opinion in Nephrology and Hypertension
IS - 5
ER -