Atrial natriuretic peptide-induced microalbuminuria is associated with endothelial dysfunction in noncomplicated type 1 diabetes patients.
BACKGROUND
Microalbuminuria reflects widespread vascular dysfunction in type 1 diabetes mellitus and results from increased glomerular sieving caused by changes in transglomerular pressure and/or permselectivity characteristics of the glomerular basement membrane. Increased tubular reabsorption or degradation of albumin will offset an early increase in albuminuria. We hypothesized that the infusion of atrial natriuretic peptide (ANP) as a tool to increase glomerular permeability might uncover changes in permselectivity in patients with uncomplicated type 1 diabetes.


METHODS
We investigated whether these patients were characterized by endothelial and/or vascular dysfunction. We therefore studied 46 normoalbuminuric patients (urinary albumin excretion [UAE] < 10 microg/min) with type 1 diabetes and 44 healthy controls. Measurements of renal hemodynamics and albuminuria were performed before (baseline) and during the infusion of ANP (0.01 microg/kg/min). On a separate occasion, endothelial function was assessed by the intra-arterial infusion of acetylcholine (ACh), an endothelial-dependent vasodilator.


RESULTS
At baseline, glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were greater in patients with diabetes (GFR, 121 +/- 3 versus 106 +/- 2 mL/min/1.73 m(2); ERPF, 558 +/- 16 versus 527 +/- 13 mL/min/1.73 m(2); P < 0.001). The infusion of ANP increased filtration fraction. There were no differences in these responses between groups. UAE was significantly greater in patients with diabetes after the ANP infusion (15.8 +/- 1.4 [+183%] versus 9.5 +/- 1.3 microg/min [+96%]; P < 0.01). A subgroup of patients with diabetes with an enhanced albuminuric response (change in UAE > 2 SD of controls) to ANP infusion (mean UAE, 30.3 +/- 1.0 microg/min; 425% +/- 61%) was characterized by a diminished vasodilatory response to ACh (maximal forearm blood flow, 17.2 +/- 2.9 [+563%] versus 26.3 +/- 2.3 mL/min/dL [+800%] in patients with diabetes with a normal albuminuric response; P < 0.05).


CONCLUSIONS
In a subgroup of patients with uncomplicated type 1 diabetes, an increase in glomerular permselectivity can be unmasked by the infusion of ANP. These patients are characterized by a diminished vascular response to ACh.
Vervoort
Gerald
G
Department of Internal Medicine, University Medical Center Nijmegen, Nijmegen, The Netherlands. g.vervoort@aig.azn.nl
Wetzels
Jack F
JF
Lutterman
Jos A
JA
Bravenboer
Bert
B
Berden
Jo H
JH
Smits
Paul
P
D000328:Adult; D000419:Albuminuria / Q000209:etiology* / Q000378:metabolism; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D003922:Diabetes Mellitus, Type 1 / Q000150:complications*; D004231:Diuresis / Q000187:drug effects / Q000502:physiology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects / Q000502:physiology; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007444:Inulin / Q000097:blood; D007677:Kidney Function Tests; D007684:Kidney Tubules / Q000098:blood supply / Q000187:drug effects; D008297:Male; D009318:Natriuresis / Q000187:drug effects / Q000502:physiology; D012039:Regional Blood Flow / Q000187:drug effects
D009320:Atrial Natriuretic Factor; D007444:Inulin