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October 23, 2008Diabetes Care40 citationsOpen Access

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

DCDavid Z.I. CherneyAKAna KonvalinkaBZBernard Zinman

Key Result

Ruboxistaurin 32 mg daily for 8 weeks did not significantly alter renal hemodynamic function compared to placebo during clamped euglycemia or hyperglycemia in patients with type 1 diabetes.

Study Design

Type

RCT (n=20)

Randomization

2:1

Structured PICO

Does ruboxistaurin improve renal hemodynamic function and urinary biomarkers in albuminuric subjects with type 1 diabetes on renin angiotensin system blockade?

P
Population
n=20 albuminuric subjects with type 1 diabetes treated with renin angiotensin system blockade
I
Intervention
Ruboxistaurin 32 mg daily for 8 weeks
C
Comparator
Placebo for 8 weeks
O
Outcome
Renal hemodynamic function and urinary biomarkers (monocyte chemoattractant protein-1 [MCP-1] and epidermal growth factor) measured during clamped euglycemia or hyperglycemiasurrogate

In a pilot study of type 1 diabetics on RAS blockade, ruboxistaurin did not significantly alter renal hemodynamics overall, though post hoc analyses suggest modest effects dependent on baseline GFR and glycemia.

Limitations

  • pilot study
  • post hoc analysis

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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Cite This Study

Cherney et al. (2008) conducted an RCT in Type 1 diabetes with albuminuria (n=20). Ruboxistaurin vs. Placebo was evaluated on Renal hemodynamic function and urinary biomarkers (MCP-1 and epidermal growth factor). Ruboxistaurin 32 mg daily for 8 weeks did not significantly alter renal hemodynamic function compared to placebo during clamped euglycemia or hyperglycemia in patients with type 1 diabetes.

synapsesocial.com/papers/6a0d1dc0e49726ca0cd9a21fhttps://doi.org/10.2337/dc08-1609
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