Pathophysiology of spontaneous hypercalciuria in laboratory rats. Role of deranged vitamin D metabolism.
Recent data suggest a causal role of deranged 1,25(OH)2D metabolism in the syndrome of idiopathic hypercalciuria. To test this hypothesis, we evaluated if vitamin D availability and/or increased serum 1,25(OH)2D were critical for the expression of hypercalciuria in laboratory rats. Ca balance, serum 25OHD3, and 1,25(OH)2D3 were studied in D-deprived (-D) and D-repleted (+D) male progeny (p) born to normocalciuric (NC) and spontaneously hypercalciuric (SH) rats. 7 of the 14 pSH and 2 of 21 pNC had SH, which was defined as urinary Ca greater than two standard deviations above the mean of values for control animals on days 5 and 6 of a low Ca +D diet (1.19 vs. 0.58 mg/d, P less than 0.001). Fasting serum Ca and 25OHD3 were similar to control. Serum 1,25(OH)2D3 was elevated in these nine SH rats (232 vs. 145 pg/ml, P less than 0.005). However, during vitamin D deprivation, their Ca excretion was also increased (1.53 vs. 0.45 mg/d, P less than 0.001), despite comparably reduced serum 1,25(OH)2D3 (102 vs. 106 pg/ml) and undetectable serum 25OHD3. Net intestinal Ca absorption on a low Ca diet was comparable during D repletion (-0.75 vs. -0.82 mg/d) or D deprivation (-0.80 vs. -2.15 mg/d), excluding primary hyperabsorption as the mediator of the hypercalciuria. Mild hypophosphatemia was present in SH on +D (5.8 vs. 6.9 mg/dl, P less than 0.005) and -D diets (6.2 vs. 7.9 mg/dl, P less than 0.005), and was associated with higher rates of cyclic adenosine monophosphate excretion (32.8 vs. 26.9 and 48.5 vs. 41.0 nmol/mg of creatinine, respectively). Spontaneous hypercalciuria is therefore dissociable from increased Ca absorption, serum levels of 25OHD3, or 1,25(OH)2D3. The data are most compatible with the hypothesis of a renal Ca leak which stimulates parathyroid hormone activity and increases serum 1,25(OH)2D3, if provided adequate 25OHD3 as substrate.
D000818:Animals; D002112:Calcifediol / Q000097:blood; D002117:Calcitriol / Q000097:blood; D002118:Calcium / Q000652:urine*; D004032:Diet; D007408:Intestinal Absorption; D008297:Male; D010710:Phosphates / Q000097:blood; D051381:Rats; D011918:Rats, Inbred SHR; D014807:Vitamin D / Q000378:metabolism*
D010710:Phosphates; D014807:Vitamin D; D002117:Calcitriol; D002112:Calcifediol; D002118:Calcium