1,25(OH)2D3-Enhanced hypercalciuria in genetic hypercalciuric stone-forming rats fed a low calcium diet.

1,25(OH)2D3-Enhanced hypercalciuria in genetic hypercalciuric stone-forming rats fed a low calcium diet. Am J Physiol Renal Physiol. 2013 Aug 7; Authors: Frick KK, Asplin JR, Krieger NS, Culbertson CD, Asplin DM, Bushinsky DA Abstract The inbred genetic hypercalciuric stone-forming (GHS) rats exhibit many features of human idiopathic hypercalciuria and have elevated levels of vitamin D receptors (VDR) in calcium (Ca) transporting organs. On a normal Ca diet, 1,25(OH)2D3 (1,25D) increases urine (U) Ca to a greater extent in GHS than in controls (SD). The additional UCa may result from an increase in intestinal Ca absorption and/or bone resorption. To determine the source, we asked whether 1,25D would increase UCa in GHS fed a low Ca (0.02%) diet. With 1,25D, UCa in SD increased from 1.2±0.1 to 9.3±0.9 mg/d and increased more in GHS from 4.7±0.3 to 21.5±0.9 mg/d (p<0.001). In GHS rats on LCD with or without 1,25D, UCa far exceeded daily Ca intake (2.6 mg/d). While the greater excess in UCa in GHS rats must be derived from bone mineral, there may also be a 1,25D-mediated decrease in renal tubular Ca reabsorption. RNA expression of the components of renal Ca transport indicated that 1,25D administration results in a suppression of klotho, an activator of the renal Ca reabsorption channel TRPV5, in both SD and GHS rats. This fall in klotho would decrease tubular reabsorption of the 1,25D-induced bone Ca release. Thus the greater increase in ...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research