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

Abstract

OBJECTIVE—The aim of this study was to examine the effect of protein kinase Cβ inhibition with ruboxistaurin on renal hemodynamic function and urinary biomarkers (monocyte chemoattractant protein-1 [MCP-1] and epidermal growth factor) in renin angiotensin system blockade-treated type 1 diabetic subjects. RESEARCH DESIGN AND METHODS—Albuminuric subjects were randomized (2:1) to ruboxistaurin (32 mg daily; n = 13) or placebo (n = 7) for 8 weeks. Renal hemodynamic 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.