An Experimental Human Model of 1,25-Dihydroxyvitamin D-Mediated Hypercalciuria*

Abstract

An increase in fasting calcium excretion occurs in hypercalciuric patients and has been interpreted by many investigators as evidence for a primary renal tubular leak of calcium. In a recent series of 50 patients with absorptive hyper-calciuria, we found a mean increase in fasting fractional calcium excretion (calcium clearance) and provided data suggesting that this leak of calcium was secondary to intestinal hyperabsorption of calcium and suppression of parathyroid secretion. To examine this question, a model of 1,25-dihydroxyvitamin D [l,25-(OH)₂D]-mediated hypercalciuria was created by administering a large dose of 1,25-(OH)₂D to normal subjects. In addition to the expected features of absorptive hypercalciuria during 1,25-(OH)₂D administration, the subjects had an increase in fasting calcium excretion and a marked increase in calcium excretion during a restricted calcium diet, points that might be interpreted as favoring a resorptive and/or renal component to the net hypercalciuria. However, total hydroxyproline excretion remained unchanged (18.0 vs. 19.0 mg/g creatinine), and the increase in fasting calcium excretion was found to reflect an increase in calcium clearance; the latter was inversely correlated with parathyroid function, as determined by fasting measurements of nephrogenous cAMP excretion (r = −0.77; P < 0.01). We conclude that measurements of calcium excretion in the fasting state or on a restricted calcium diet do not represent valid criteria for differential diagnosis of the hypercalciurias.