Effect of direct renin inhibition on renal hemodynamic function, arterial stiffness, and endothelial function in humans with uncomplicated type 1 diabetes: a pilot study.
OBJECTIVE
Blockade of the renin-angiotensin system (RAS) plays an important role in preventing end-organ injury associated with diabetes. The recent development of direct renin inhibitors (DRIs) provides a new approach to block the RAS, but the effects of DRIs on renal and systemic vascular function in uncomplicated type 1 diabetes have not been elucidated.


METHODS
Renal hemodynamic function (inulin and paraaminohippurate clearance), augmentation index and pulse wave velocity, endothelial dependent vasodilatation (flow-mediated dilation [FMD]), and endothelial independent vasodilatation (response to sublingual nitroglycerin) were evaluated before and after administration of aliskiren (300 mg daily for 30 days) in 10 adult subjects with uncomplicated type 1 diabetes during clamped euglycemia (4-6 mmol/l) and hyperglycemia (9-11 mmol/l).


RESULTS
In response to the DRI, plasma renin activity decreased (from 0.40 to 0.13 ng . ml(-1) . h(-1), P < 0.05) and plasma renin increased (from 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). The carotid augmentation index during clamped euglycemia decreased (from 26 +/- 6 to 20 +/- 5%, P < 0.05) as did pulse wave velocity during clamped hyperglycemia (from 7.8 +/- 0.6 to 6.8 +/- 0.5 m/s, P < 0.05). In response to the DRI, FMD increased during both clamped euglycemia (from 1.92 +/- 1.13 to 5.55 +/- 0.81%) and hyperglycemia (from 1.86 +/- 0.98 to 5.63 +/- 0.62) as did the vasodilatory response to sublingual nitroglycerin.


CONCLUSIONS
DRIs exert a renal vasodilatory effect and improve 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 diabetes.
Cherney
David Z I
DZ
Division of Nephrology, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada. david.cherney@uhn.on.ca
Lai
Vesta
V
Scholey
James W
JW
Miller
Judith A
JA
Zinman
Bernard
B
Reich
Heather N
HN
D000328:Adult; D000419:Albuminuria / Q000652:urine*; D015992:Body Mass Index; D001835:Body Weight; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000503:physiopathology*; D004044:Dietary Proteins / Q000378:metabolism; D004730:Endothelium, Vascular / Q000503:physiopathology*; D004958:Estradiol / Q000097:blood; D005260:Female; D006439:Hemodynamics / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018579:Patient Selection; D010865:Pilot Projects; D012083:Renin / Q000502:physiology*; D012084:Renin-Angiotensin System / Q000502:physiology; D000092502:Renin Inhibitors
D004044:Dietary Proteins; D004958:Estradiol; D012083:Renin; D000092502:Renin Inhibitors