title: A consideration of the hormonal basis and phosphate leak hypothesis of absorptive hypercalciuria.
abstract: Fifty patients with absorptive hypercalciuria (AH), 25 normal subjects (NS), and 25 nonhypercalciuric patients with stone disease (NHSF) were studied using an oral calcium tolerance test and 24-h urine collections on both a restricted and an unrestricted calcium intake. Mean (+/- SD) fasting fractional calcium excretion was increased in the patients with AH (2.7 +/- 1.1% vs. 1.4 +/- 0.6% in the NS; P less than 0.001) and was negatively correlated with fasting nephrogenous cAMP, suggesting that this renal calcium leak was secondary to parathyroid suppression. Plasma 1,25-dihydroxyvitamin D [1,25-(OH)2D] was elevated in 80% of patients with AH and was high normal in the remaining 20%. Ten patients, selected on the basis of results for 1,25-(OH)2D greater than 4 SD from the normal mean, displayed a particularly severe pattern of abnormalities, including mild hypercalcemia in two patients. Pooled data from the NS and patients with AH revealed a significant negative correlation between the plasma concentration of 1,25-(OH)2D and the renal phosphate threshold (r = -0.40; P less than 0.001), but this correlation lost significance when the NHSF were substituted for the NS as a control group (r = -0.07; P = NS). These findings 1) provide a pathophysiological basis for the increase in fasting calcium excretion commonly observed in hypercalciuric patients, and 2) stress the importance of circulating 1,25-(OH)2D in the pathogenesis of the syndrome, but 3) fail to support the phosphate leak theory of pathogenesis.
mesh_terms: D000328:Adult; D002117:Calcitriol / Q000097:blood; D002118:Calcium / Q000652:urine*; D002128:Calcium Metabolism Disorders / Q000378:metabolism / Q000503:physiopathology; D005215:Fasting; D005260:Female; D006801:Humans; D007669:Kidney Calculi / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010280:Parathyroid Glands / Q000503:physiopathology; D010710:Phosphates / Q000378:metabolism*
chemical_list: D010710:Phosphates; D002117:Calcitriol; D002118:Calcium