MICROALBUMINURIA REFLECTS A GENERALIZED TRANSVASCULAR ALBUMIN LEAKINESS IN CLINICALLY HEALTHY-SUBJECTS

1. In epidemiological studies microalbuminuria, i,e, slightly elevated urinary albumin excretion rate, predicts increased atherosclerotic va scular morbidity and mortality, This study aimed to test the hypothesi s that microalbuminuria in clinically healthy subjects is associated w ith a systemic transvascular albumin leakiness. In animal experiments the outflux of albumin and lipids to the arterial wall are highly corr elated, and both are elevated in atherosclerosis. 2. All participants were recruited at random from a population-based epidemiological study , where the upper decile of urinary albumin excretion rate was 6.6 mu g/min. Twenty-seven patients with persistent microalbuminuria (urinary albumin excretion rate 6.6-150 mu g/min), and 56 age- and sex-matched control subjects with persistent normoalbuminuria (UAER less than or equal to 6.6 mu g/min) were studied. 3. The systemic transvascular alb umin leakage was measured as the fractional disappearance rate of I-12 5-labelled albumin from the total plasma compartment in Ih after intra venous injection. 4. The fractional disappearance rate of albumin,from the plasma compartment was higher in the microalbuminuric than in the normoalbuminuric group [5.8 (95% confidence interval 5.3-6.2; n=27) v ersus 5.0 (4.6-5.5; n=56)%/h, P<0,05]., The positive correlation betwe en urinary albumin excretion rate on continuous scale (logarithmically transformed) and the fractional disappearance rate of albumin from th e plasma compartment [slope 0.4 (95% confidence interval 0.1-0.7; n=83 ), r=0.29, P<0.005] was independent of age, sex, smoking status, blood pressure, body size, plasma volume, plasma albumin concentration and concentrations of blood glucose, serum insulin and serum lipids. 5. In conclusion, microalbuminuria is an independent marker of systemic tra nsvascular albumin leakiness in clinically healthy subjects, This find ing may partly explain the increased atherosclerotic vascular morbidit y and mortality in microalbuminuric subjects, It is suggested that the observed transvascular leakiness, in addition, may cause increased li pid insudation to the arterial walls.