Effect of Protein Kinase Cβ Inhibition on Renal Hemodynamic Function and Urinary Biomarkers in Humans With Type 1 Diabetes: A Pilot Study

OBJECTIVE - The aim of this study was to examine the effect of protein kinase C beta inhibition with ruboxistaurin on renal hemodynamic function and urinary biomarkers (monocyte chemoattractant protem-1 [MCP-1] and epidermal growth factor) in renin angiotensin system blockade-treated type I diabetic subjects. RESEARCH DESIGN AND METHODS - Albuminuric subjects were randomized (2: 1) to ruboxistaurin (32 mg daily; it = 13) or placebo (n = 7) for 8 weeks. Renal hemodynainic function was measured during clamped euglycemia or hyperglycemia and before and after ruboxistaurin or placebo. RESULTS - Ruboxistaurin was not associated with between-group differences during clamped euglycemia or hyperglycemia. In a post hoc analysis comparing hyperfilterers with normofilterers during euglycemia, glomerular filtration rate and MCP-1 decreased, whereas the epidermal growth factor-to-MCP-1 ratio increased in hyperfilterers versus normofilterers (all P < 0.05). CONCLUSIONS - The effect of ruboxistaurin is modest and dependent, at least in part, on the level of ambient glycemia and baseline glomerular filtration rate.