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

• Published in: Diabetes care Vol. 32; no. 1; p. 91
• Main Authors: Cherney, David Z I, Konvalinka, Ana, Zinman, Bernard, Diamandis, Eleftherios P, Soosaipillai, Anton, Reich, Heather, Lorraine, Joanne, Lai, Vesta, Scholey, James W, Miller, Judith A
• Format: Journal Article
• Language: English
• Published: Alexandria American Diabetes Association 01.01.2009
• Subjects: Biomarkers; Hyperglycemia; Kinases; Medical research; Rodents; Studies
• ISSN: 0149-5992
• DOI: 10.2337/dc08-1609

The aim of this study was to examine the effect of protein kinase Cß 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. 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. 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). The effect of ruboxistaurin is modest and dependent, at least in part, on the level of ambient glycemia and baseline glomerular filtration rate.