Vitamin D and calcium receptors: links to hypercalciuria.
OBJECTIVE
In idiopathic hypercalciuria, patients have increased intestinal Ca absorption and decreased renal Ca reabsorption, with either elevated or normal serum levels of 1,25-dihydroxyvitamin D. As 1,25-dihydroxyvitamin D exerts its biologic effects through interactions with the vitamin D receptor, we examine the actions of this receptor and 1,25-dihydroxyvitamin D in animals with genetic hypercalciuria.


RESULTS
In genetic hypercalciuric stone-forming rats intestinal calcium transport is increased and renal calcium reabsorption is reduced, yet serum 1,25-dihydroxyvitamin D levels are normal. Elevated intestinal and kidney vitamin D receptors suggest that increased tissue 1,25-dihydroxyvitamin D-vitamin D receptor complexes enhance 1,25-dihydroxyvitamin D actions on intestine and kidney, and vitamin D-dependent over-expression of renal calcium-sensing receptor alone can decrease tubule calcium reabsorption. In TRPV5-knockout mice, ablation of the renal calcium-influx channel decreases tubular calcium reabsorption, and secondary elevations in 1,25-dihydroxyvitamin D increase intestinal calcium transport.


CONCLUSIONS
1,25-Dihydroxyvitamin D or vitamin D receptor may change intestinal and renal epithelial calcium transport simultaneously or calcium-transport changes across renal epithelia may be primary with a vitamin D-mediated secondary increase in intestinal transport. The extent of homology between the animal models and human idiopathic hypercalciuria remains to be determined.
Bai
Shaochun
S
Section of Endocrinology, University of Chicago Pritzker School of Medicine, Chicago, Illinois 60637, USA.
Favus
Murray J
MJ
D000818:Animals; D001692:Biological Transport / Q000235:genetics; D002117:Calcitriol / Q000378:metabolism*; D015220:Calcium Channels / Q000172:deficiency / Q000378:metabolism*; D002128:Calcium Metabolism Disorders / Q000235:genetics / Q000378:metabolism*; D004848:Epithelium / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D007674:Kidney Diseases / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D051381:Rats; D044169:Receptors, Calcium-Sensing / Q000235:genetics / Q000378:metabolism*; D050916:TRPV Cation Channels / Q000172:deficiency / Q000378:metabolism*
D015220:Calcium Channels; D044169:Receptors, Calcium-Sensing; D050916:TRPV Cation Channels; C492240:Trpv5 protein, mouse; D002117:Calcitriol