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Effect of protein kinase Cbeta inhibition on renal hemodynamic function and urinary biomarkers in humans with type 1

David Z I Cherney1, Ana Konvalinka, Bernard Zinman

  • 1Division of Medicine, University Health Network, Toronto, Canada. david.cherney@utoronto.ca

Diabetes Care
|October 24, 2008
PubMed
Abstract

Insights

Ruboxistaurin did not significantly alter renal hemodynamics in type 1 diabetes patients. However, it showed potential in reducing monocyte chemoattractant protein-1 (MCP-1) in hyperfiltering individuals.

Area of Science:

  • Nephrology
  • Endocrinology
  • Pharmacology

Background:

  • Type 1 diabetes is associated with renal complications.
  • Renin-angiotensin system (RAS) blockade is a standard treatment.
  • Protein kinase Cbeta (PKCbeta) is implicated in diabetic nephropathy.

Purpose of the Study:

  • To investigate the impact of ruboxistaurin, a PKCbeta inhibitor, on renal hemodynamics.
  • To assess changes in urinary biomarkers, including monocyte chemoattractant protein-1 (MCP-1) and epidermal growth factor (EGF).
  • To evaluate these effects in type 1 diabetic subjects receiving RAS blockade.

Main Methods:

  • Randomized trial comparing ruboxistaurin (32 mg/day) versus placebo for 8 weeks in albuminuric type 1 diabetic patients.
  • Renal hemodynamic function assessed under euglycemic and hyperglycemic conditions.
  • Urinary MCP-1 and EGF levels measured.

Main Results:

  • Ruboxistaurin did not show significant between-group differences in renal hemodynamics under clamped euglycemia or hyperglycemia.
  • Post hoc analysis revealed decreased glomerular filtration rate (GFR) and MCP-1 in hyperfilterers compared to normofilterers during euglycemia.
  • The EGF-to-MCP-1 ratio increased in hyperfilterers versus normofilterers (P < 0.05).

Conclusions:

  • The therapeutic effect of ruboxistaurin appears modest.
  • Its efficacy may depend on glycemic control and baseline GFR.
  • Further research is needed to clarify ruboxistaurin's role in diabetic kidney disease management.

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