The Effect of Direct Renin Inhibition on Renal Hemodynamic Function, Arterial Stiffness and Endothelial Function in Humans with Uncomplicated Type 1 Diabetes Mellitus: A Pilot Study

  1. David Z.I. Cherney, MD, PhD (david.cherney{at}uhn.on.ca)1,
  2. Vesta Lai, RN1,
  3. James W. Scholey, MD1,
  4. Judith A. Miller, MD1,
  5. Bernard Zinman, MD2 and
  6. Heather N. Reich, MD, PhD1
  1. 1 Division of Nephrology, Toronto General Hospital, University of Toronto
  2. 2 Samuel Lunenfeld Research Institute, University of Toronto

    Abstract

    Introduction: Blockade of the renin angiotensin system (RAS) plays an important role in preventing end-organ injury associated with diabetes mellitus (DM). The recent development of direct renin inhibitors (DRI) provides a new approach to block the RAS, but the effect of DRIs on renal and systemic vascular function in uncomplicated type 1 DM have not been elucidated.

    Methods: Renal hemodynamic function (inulin, paraaminohippurate clearance), augmentation index and pulse wave velocity, endothelial dependent vasodilatation (FMD) and endothelial independent vasodilatation (response to sublingual nitroglycerin) were evaluated before and after taking aliskiren (300 mg daily for 30 days) in 10 adult subjects with uncomplicated type 1 DM during clamped euglycemia (4-6 mmol/L) and hyperglycemia (9-11 mmol/L).

    Results: In response to DRI, plasma renin activity decreased (0.40 to 0.13 ng/mL/h, p<0.05) and plasma renin increased (5.2 to 75.0 ng/L, p<0.05). Peripheral and central blood pressures decreased and effective renal plasma flow and glomerular filtration rate increased during clamped euglycemia and hyperglycemia (p<0.05). Carotid augmentation index during clamped euglycemia decreased (26±6% to 20±5%, p<0.05) as did pulse wave velocity during clamped hyperglycemia (7.8±0.6 m/s to 6.8±0.5 m/s, p<0.05). In response to DRI, FMD increased during both clamped euglycemia (1.92±1.13% to 5.55±0.81%) and hyperglycemia (1.86±0.98% to 5.63±0.62) as did the vasodilatory response to sublingual nitroglycerin.

    Conclusions: DRI exerts a renal vasodilatory effect and improves parameters of systemic vascular function, suggesting that blockade of the RAS with this new class of agents has important functional effects in subjects with uncomplicated type 1 DM.

    Footnotes

      • Received July 16, 2009.
      • Accepted October 22, 2009.

    This Article

    1. Diabetes Care
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