Microalbuminuria and Transcapillary Albumin Leakage in Essential Hypertension

Abstract

Abstract-Microalbuminuria (an increased urinary albumin excretion that is not detectable by the usual dipstick methods for macroproteinuria) predicts cardiovascular events in essential hypertensive patients. A possible reason for this behavior is that albumin leaks through exaggeratedly permeant glomeruli exposed to the damaging impact of subclinical atherogenesis. To evaluate this possibility, the transcapillary escape rate of albumin (TER alb , the 1-hour decline rate of intravenous 125 I-albumin), a parameter that estimates the integrity of systemic capillary permeability, albuminuria, blood pressure, echocardiographic left ventricular mass, lipids, and body mass index were measured in 73 uncomplicated, glucose-tolerant men with essential hypertension and normal renal function; 53 were normoalbuminuric, and 20 were microalbuminuric. Twenty-one normotensive age-matched male subjects were the controls. TER alb was higher in hypertensives, a behavior explained in part by a positive correlation with blood pressure values, although body mass index, lipids, and left ventricular mass showed no association. Transcapillary albumin leakage values did not differ between normoalbuminuric and microalbuminuric patients and were unrelated to albuminuria. Blood pressure, particularly systolic, and cardiac mass were higher in microalbuminuric patients in whom albuminuria correlated with both cardiovascular variables and indicated the influence of the hemodynamic load on urinary albumin levels. Thus, TER alb , a parameter influenced by the permeability surface area product for macromolecules and the filtration power across the vascular wall, is altered in essential hypertensives. However, this abnormality is dissociated from the amount of albuminuria, which is contrary to the hypothesis that a higher albumin excretion reflects a greater degree of systemic microvascular damage in essential hypertension. (Hypertension. 1999;34:491-495.) Key Words: albuminuria Ⅲ hypertension, essential Ⅲ cardiac mass Ⅲ blood pressure Ⅲ capillary permeability M icroalbuminuria (ie, an abnormal urinary albumin excretion [UAE] in a range not detectable by the usual dipstick methods for urinary protein) is associated with a greater incidence of cardiovascular events in hypertensive patients 1-3 and predicts all-cause and coronary disease morbidity and mortality independently from other cardiovascular risk factors in nondiabetic populations. 4 -7 However, the reasons why a renal parameter behaves as a marker of atherosclerotic cardiovascular disease in hypertension remain obscure. One concept postulates that more albumin leaks through exaggeratedly permeant glomeruli that reflect the systemic damaging impact of subclinical atherogenesis, 8 a process characterized by a diffuse involvement of the entire vascular system. 9 This hypothesis, which was originally formulated to account for the higher cardiovascular morbidity rate in diabetic patients, 8 may also apply to essential hypertensive patients, 10 but no information is available on this issue at th...

Effect of hypertension and its reverse on serum nitric oxide concentration and vascular permeability in two-kidney one-clip hypertensive rats

“…However, we did not find any difference in endothelial permeability between these groups. It seems that elevated blood pressure and disruption of the starling equilibrium could increase endothelial permeability (Parving and Gyntelberg 1973); however, in this study, preservation of endothelial permeability in 2K1C hypertensive group indicated that change of hemodynamic forces in hypertension does not contribute in endothelial permeability (Pedrinelli et al 1999). In agreement to our results, a recent clinical study evaluated systemic capillary permeability using TERalb (another parameter for estimation of capillary permeability) and found that systemic capillary permeability was not different between normotensive and hypertensive group (Dell'Omo et al 2004).…”

Dissociation between microalbuminuria and common carotid thickness in essential hypertensive men

“…31 On one hand, consistent evidence does suggest that hypertensive microalbuminuria is associated with circulating markers of endothelial dysfunction, [32][33][34][35] including von Willebrand Factor, an endothelial haemostatic factor and a predictor of cardiovascular death. 36 On the other hand, however, urine albumin was dissociated from both the transcapillary 125 I-albumin escape rate, a measure of systemic capillary permeability, 28,37 and forearm vasodilatation to acetylcholine, 38 a compound that releases nitric-oxide from endothelial cells. 31 Thus, microalbuminuria may not reflect defects of specific endothelial functions such as macromolecular permeability 39 and nitric-oxide release, 31 but rather represent a non-specific response to inflammatory stimuli, in itself a cardiovascular risk factor.…”

A blood pressure independent association between glomerular albumin leakage and electrocardiographic left ventricular hypertrophy. The LIFE Study

“…3,4 In mild, uncomplicated hypertension the main determinant of urine albumin excretion is thought to be increased haemodynamic load, 2,5,6 whereas increased glomerular vascular permeability as part of a generalised vascular dysfunction 7 is thought to be increasingly important for elevation of urine albumin excretion in moderate to severe hypertension, especially if associated with metabolic abnormalities. 8,9 Although elevated urine albumin excretion has been associated with many known cardiovascular risk factors like blood pressure (BP), 2 smoking, 10 serum homocysteine, 11 racial differences, 12 LV hypertrophy, 6 plasma glucose and serum insulin, 9 elevated urine albumin excretion has in some studies been demonstrated to be an independent predictor of cardiovascular disease and increased all-cause mortality in non-diabetic subjects as well as in patients with hypertension. 4,13,14 In hypertensive patients with LV hypertrophy on electrocardiography (ECG) we recently found that elevated urine albumin excretion assessed as increased urine albumin/creatinine ratio (UACR) and LV mass assessed by ECG were related to high BP suggesting parallel cardiac and glomerular vascular damage.…”