Graded nephron mass reduction and renal synthesis of 1,25-dihydroxyvitamin D3 in the rat

The effect of graded nephron mass reduction by partial nephrectomy and the influence of parathyroid hormone and dietary phosphorus (P) on the production of 1,25-dihydroxy-vitamin D [1,25(OH)2D] were studied in vitamin D deficient rats. At 48 hours (acute experiments) or 2 weeks (chronic experiment) after partial nephrectomy, the rates of [3H]1,25(OH)2D production from [3H]25 hydroxyvitamin D (25-OHD) were measured in vivo. The production of 1,25(OH)2D decreased in proportion to the remaining nephron mass, and it was not greater in chronic experiments than in acute experiments at any level of nephron mass reduction. By contrast, plasma creatinine was elevated in 5 of 6 nephrectomized rats in acute, but not in chronic, experiments, suggesting the compensatory mechanism for renal excretory function but not for 1,25(OH)2D production. Further, at any level of nephron mass reduction, the production of this active metabolite was not greater in rats fed low P diet than those fed normal or high P diets. Thyroparathyroidectomy at 12 hours prior to a dose of [3H]-25)OHD suppressed 1,25(OH)2D production at any level of nephron mass reduction in rats fed normal or high P diet. These data suggest that in both experimental acute and chronic renal failure 1,25(OH)2D production is proportional to residual nephron mass and that parathyroid hormone may enhance the metabolism of 25OHD in renal failure and also may be critical for 1,25(OH)2D in normal or high P diet.