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(Circulation. 2004;110:821-825.)
© 2004 American Heart Association, Inc.

Original Articles

Endothelial Dysfunction and Mild Renal Insufficiency in Essential Hypertension

From the Internal Medicine and Cardiovascular Diseases Unit (F.P., R.M.), Department of Experimental and Clinical Medicine G. Salvatore, University Magna Graecia of Catanzaro, Catanzaro, Italy, and CNR-IBIM (G.T., C.Z.), National Research Council Institute of Biomedicine, Clinical Epidemiology and Physiopathology of Renal Diseases and Hypertension, Reggio Calabria, Italy.

Correspondence to Prof Carmine Zoccali, CNR-IBIM, Istituto di Biomedicina, Epidemiologia Clinica e Fisiopatologia, delle Malattie Renali e dell’Ipertensione Arteriosa, c/o Divisione di Nefrologia–Ospedali Riuniti, Via Vallone Petrara, 89124 Reggio Calabria, Italy. E-mail carmine.zoccali{at}tin.it

Received November 3, 2003; de novo received February 6, 2004; revision received April 1, 2004; accepted April 14, 2004.

Background— Mild to moderate renal insufficiency in individuals with essential hypertension is currently considered the expression of a renal microvasculopathy characterized by preglomerular arteriolar involvement and tubulo-interstitial changes. Whether endothelial dysfunction plays a role in this alteration is still undefined.

Methods and Results— We investigated the relationship between endothelial function (hemodynamic response to acetylcholine [ACh] in the forearm) and renal function in 500 patients with uncomplicated, never-treated, essential hypertension and serum creatinine within the normal range (ie, 1.5 mg/dL). Serum creatinine, creatinine clearance, and estimated glomerular filtration rate (GFR, by the Modification of Diet in Renal Disease formula) were related to the forearm blood flow response to ACh (all P0.003), and these relationships held true in multiple regression analyses that included age, gender, systolic pressure, serum cholesterol and glucose, smoking, and body mass index. Accordingly, on multiple logistic regression analysis, the risk of moderate renal dysfunction (ie, an estimated GFR <60 mL · min^–1 · 1.73 m^–2) was 64% lower (OR 0.36, 95% CI 0.18 to 0.70) in patients in the third ACh tertile (ie, those showing the higher vasodilatory response) than in those in the first tertile (ie, showing the lower response). C-reactive protein was related directly to serum creatinine and inversely to GFR and vasodilatory response to ACh, which suggests that endothelial dysfunction is a possible mechanism linking inflammation and impaired renal function in essential hypertension.

Conclusions— An impaired vasodilatory response to ACh appears to be associated with renal function loss in patients with essential hypertension. This association suggests that systemic endothelial dysfunction is involved in mild to moderate renal insufficiency in patients with uncomplicated essential hypertension.

Key Words: acetylcholine • endothelium • kidneys

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