Prevalence, pathogenesis, and functional significance of aldosterone deficiency in hyperkalemic patients with chronic renal insufficiency

Abstract

Plasma and urinary aldosterone levels and plasma renin activity (PRA) were measured to determine the prevalence, pathogenesis, and functional significance of aldosterone deficiency in hyperkalemic patients with chronic renal insufficiency (creatinine clearance, 31 ± 2 ml/min). In 31 such patients, urinary aldosterone (UAldoV) ranged from 0.8 to 10.9 μg/24 hr (normal subjects, 4.2 to 16.6 μg/24 hr; N = 29). Because potassium ordinarily stimulates aldosterone secretion, UAldoV was expressed as a function of serum potassium (UA1doV/SK). In 23 patients, UAldoV/SK was subnormal (subgroup A); in 8 patients, UAldoV/SK was within the normal range (subgroup B). In both groups, UAldoV and SK correlated positively, but UAldoV was lower in subgroup A at any SK. Serum potassium correlated with urinary potassium excretion (UKV) in both subgroups, but for any UKV, SK was greater in subgroup A. In all but 1 patient in subgroup B, PRA was within normal limits. In subgroup A, 19 patients had subnormal PRA. In these patients (hyporeninemic hypoaldosteronism), stimulation of PRA by sodium chloride depletion was blunted, but plasma aldosterone concentration (PAldo) and PRA correlated positively (PAldo, 10.8 x PRA + 5.1; r = 0.97; P < 0.01), with a slope not significantly different from that in normal subjects (PAldo, 14.5 x PRA - 9.4; r = 0.98, P < 0.01). The remaining 4 patients in subgroup A had normal PRA values. Despite significantly greater values of SK in these 4 patients with normoreninemic hypoaldosteronism, PAldo was significantly lower than it was in subgroup B patients and normal subjects at all similar values of PRA. When PRA was stimulated further by sodium depletion in 2 of the 4 patients so studied, the increase in PAldo was blunted. The findings indicate that hypoaldosteronism occurs commonly (23/31 patients) in hyperkalemic patients with chronic renal insufficiency and that the deficiency of aldosterone contributes to the pathogenesis of the hyperkalemia. In most patients (83%), hypoaldosteronism could be accounted for by deficient renal secretion of renin, but in some patients (17%), renin deficiency did not appear to be present, and therefore other (unidentified) causes of aldosterone deficiency must be invoked.