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

  1. David Z.I. Cherney, MD, CM, PHD1,
  2. Ana Konvalinka, MD2,
  3. Bernard Zinman, MD3,
  4. Eleftherios P. Diamandis, MD, PHD4,
  5. Anton Soosaipillai, BSC4,
  6. Heather Reich, MD, CM, PHD1,
  7. Joanne Lorraine, MD5,
  8. Vesta Lai, RN1,
  9. James W. Scholey, MD1 and
  10. Judith A. Miller, MD, MSC, MHSC1
  1. 1Division of Medicine, University Health Network, Toronto, Canada
  2. 2Division of Nephrology, University Health Network, Toronto, Canada
  3. 3Leadership Sinai Centre for Diabetes, Samuel Lunenfeld Research Institute, Division of Medicine, Mount Sinai Hospital, Toronto, Canada
  4. 4Division of Laboratory Medicine and Pathobiology, Mount Sinai Hospital, Toronto, Canada
  5. 5Eli Lilly Canada, Toronto, Canada
  1. Corresponding author: David Z.I. Cherney, david.cherney{at}utoronto.ca

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.

Footnotes

  • Published ahead of print at http://care.diabetesjournals.org on 22 October 2008.

    Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.

    The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    • Accepted October 14, 2008.
    • Received September 3, 2008.
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  1. Published online before print October 22, 2008, doi: 10.2337/dc08-1609 Diabetes Care January 2009 vol. 32 no. 1 91-93
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