Endothelial dysfunction and subsequent decline in glomerular filtration rate in hypertensive patients

BACKGROUND: Chronic kidney disease is a risk factor for cardiovascular disease, increasing all-cause mortality. Some evidence suggests that endothelial dysfunction is present in the early stages of renal insufficiency, but no data exist about its possible role in the progression of renal disease. Thus, we prospectively evaluated the effect of endothelial function on estimated glomerular filtration rate (eGFR) in essential hypertension. METHODS AND RESULTS: We enrolled 500 never-treated uncomplicated hypertensive subjects with serum creatinine < or =1.5 mg/dL. Endothelial function was measured by strain-gauge plethysmography during intra-arterial infusion of acetylcholine and sodium nitroprusside. eGFR was calculated by use of the Chronic Kidney Disease Epidemiology Collaboration equation. The annual rate of decline of eGFR (DeltaeGFR/y) was determined as the difference between the follow-up and baseline eGFR values, with this value divided by the time interval in years. During follow-up (92.3+/-36.2 months), mean DeltaeGFR/y was 1.49+/-1.65 mL . min(-1) . 1.73 m(-)(2), with no significant differences between men and women (1.55+/-1.72 versus 1.43+/-1.58 mL . min(-1) . 1.73 m(-)(2), respectively; P=0.455). This was correlated with acetylcholine-stimulated forearm blood flow (r=-0.256, P<0.0001), creatinine (r=0.141, P=0.001), systolic blood pressure (r=-0.103, P=0.01), and eGFR (r=0.092, P=0.020). In multivariable regression analysis, forearm blood flow and systolic blood pressure remained associated with change in eGFR. On average, eGFR changed by 0.37 mL . min(-1) . 1.73 m(-)(2) for each 100% change in forearm blood flow (P<0.001) and by 0.1 mL . min(-1) . 1.73 m(-)(2) for each difference of 10 mm Hg in systolic blood pressure (P=0.032). CONCLUSIONS: We demonstrated that acetylcholine-stimulated vasodilation and systolic blood pressure were associated with eGFR loss after adjustment for other cardiovascular risk factors and antihypertensive treatment.