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Effect of protein kinase Cbeta inhibition on renal hemodynamic function and urinary biomarkers in humans with type 1 diabetes: a pilot study.

Cherney DZ, Konvalinka A, Zinman B, Diamandis EP, Soosaipillai A, Reich H, Lorraine J, Lai V, Scholey JW, Miller JA - Diabetes Care (2008)

Bottom Line: The aim of this study was to examine the effect of protein kinase Cbeta 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.Ruboxistaurin was not associated with between-group differences during clamped euglycemia or hyperglycemia.

View Article: PubMed Central - PubMed

Affiliation: Division of Medicine, University Health Network, Toronto, Canada. david.cherney@utoronto.ca

ABSTRACT

Objective: The aim of this study was to examine the effect of protein kinase Cbeta 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.

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The effect of ruboxistaurin (RBX) on GFR during euglycemia in hyperfiltration and normofiltration subjects (mean ± SEM). HF, hyperfiltration; NF, normofiltration. *P = 0.009 vs. baseline in hyperfiltration subjects. †P = 0.003 vs. response in normofiltration subjects.
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f1: The effect of ruboxistaurin (RBX) on GFR during euglycemia in hyperfiltration and normofiltration subjects (mean ± SEM). HF, hyperfiltration; NF, normofiltration. *P = 0.009 vs. baseline in hyperfiltration subjects. †P = 0.003 vs. response in normofiltration subjects.

Mentions: When analyzed on the basis of filtration status, hyperfiltration (n = 4) and normofiltration (n = 9) subjects were similar at baseline (data not shown). In hyperfiltration subjects, ruboxistaurin was associated with a decline in GFR that was significant compared with the response in normofiltration subjects (Fig. 1). When analyzed on the basis of filtration status, ruboxistaurin was associated with a decrease in MCP-1 (P = 0.041) and a rise in the EGF–to–MCP-1 ratio (P = 0.041) in hyperfiltration versus normofiltration subjects (online appendix Figures A1–A3).


Effect of protein kinase Cbeta inhibition on renal hemodynamic function and urinary biomarkers in humans with type 1 diabetes: a pilot study.

Cherney DZ, Konvalinka A, Zinman B, Diamandis EP, Soosaipillai A, Reich H, Lorraine J, Lai V, Scholey JW, Miller JA - Diabetes Care (2008)

The effect of ruboxistaurin (RBX) on GFR during euglycemia in hyperfiltration and normofiltration subjects (mean ± SEM). HF, hyperfiltration; NF, normofiltration. *P = 0.009 vs. baseline in hyperfiltration subjects. †P = 0.003 vs. response in normofiltration subjects.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2606837&req=5

f1: The effect of ruboxistaurin (RBX) on GFR during euglycemia in hyperfiltration and normofiltration subjects (mean ± SEM). HF, hyperfiltration; NF, normofiltration. *P = 0.009 vs. baseline in hyperfiltration subjects. †P = 0.003 vs. response in normofiltration subjects.
Mentions: When analyzed on the basis of filtration status, hyperfiltration (n = 4) and normofiltration (n = 9) subjects were similar at baseline (data not shown). In hyperfiltration subjects, ruboxistaurin was associated with a decline in GFR that was significant compared with the response in normofiltration subjects (Fig. 1). When analyzed on the basis of filtration status, ruboxistaurin was associated with a decrease in MCP-1 (P = 0.041) and a rise in the EGF–to–MCP-1 ratio (P = 0.041) in hyperfiltration versus normofiltration subjects (online appendix Figures A1–A3).

Bottom Line: The aim of this study was to examine the effect of protein kinase Cbeta 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.Ruboxistaurin was not associated with between-group differences during clamped euglycemia or hyperglycemia.

View Article: PubMed Central - PubMed

Affiliation: Division of Medicine, University Health Network, Toronto, Canada. david.cherney@utoronto.ca

ABSTRACT

Objective: The aim of this study was to examine the effect of protein kinase Cbeta 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.

Show MeSH
Related in: MedlinePlus