Mechanism of hypercalciuria in genetic hypercalciuric rats. Inherited defect in intestinal calcium transport.
Excessive urine calcium excretion in patients with idiopathic hypercalciuria may involve a primary increase in intestinal calcium absorption, overproduction of 1,25-dihydroxyvitamin D3 or a defect in renal tubular calcium reabsorption. To determine the mechanism of hypercalciuria in an animal model, hypercalciuria was selected for in rats and the most hypercalciuric animals inbred. Animals from the fourth generation were utilized to study mineral balance and intestinal transport in relation to levels of serum 1,25(OH)2D3. Both urine calcium excretion and net intestinal calcium absorption were greater in hypercalciuric males (HM) than in normocalciuric males (NM) and in hypercalciuric females (HF) than in normocalciuric females (NF). However, serum 1,25(OH)2D3 was lower in HM than in NM and not different in HF than in NF. Net calcium balance was more positive in HM than in NM and in HF than in NF. In vitro duodenal calcium net flux was correlated with serum 1,25(OH)2D3 in HM and HF and in NM and NF. However, with increasing serum 1,25(OH)2D3 there was greater calcium net flux in hypercalciuric rats than in normocalciuric controls. Hypercalciuria in this colony of hypercalciuric rats is due to a primary intestinal overabsorption of dietary calcium and not an overproduction of 1,25(OH)2D3 or a defect in the renal tubular reabsorption of calcium.
Bushinsky
D A
DA
Nephrology Section, Pritzker School of Medicine, University of Chicago, Illinois 60637.
Favus
M J
MJ
D000818:Animals; D002117:Calcitriol / Q000097:blood; D002118:Calcium / Q000493:pharmacokinetics / Q000652:urine*; D002136:Calcium, Dietary / Q000008:administration & dosage; D005260:Female; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism*; D008274:Magnesium / Q000493:pharmacokinetics; D008297:Male; D010758:Phosphorus / Q000493:pharmacokinetics; D051381:Rats; D011919:Rats, Inbred Strains
D002136:Calcium, Dietary; D010758:Phosphorus; D002117:Calcitriol; D008274:Magnesium; D002118:Calcium