Laboratory Investigation

Kidney International (1989) 36, 234–239; doi:10.1038/ki.1989.185

Effect of vitamin D metabolites on calcitriol metabolism in experimental renal failure

Sanjeev Patel1, Robert U Simpson1 and Chen H Hsu1

1Nephrology Division, Department of Internal Medicine and Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan, USA

Correspondence: Chen H Hsu MD, Nephrology Division, Department of Internal Medicine, 3914 Taubman Medical Center, University Hospital, Ann Arbor, Michigan 48109-0364, USA.

Received 29 July 1988; Revised 13 March 1989; Accepted 24 March 1989.

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Abstract

Effect of vitamin D metabolites on calcitriol metabolism in experimental renal failure. Previous studies from our laboratory have demonstrated that metabolic clearance rate (MCR) of calcitriol is decreased in experimental renal failure. In this experiment, we examined the effects of calcitriol, 25-hydroxyvitamin D3 (25(OH)D3) and 24,25-dihydroxyvi-tamin D3 (24,25(OH)2D3) on the MCR of calcitriol in renal failure produced in rats by partial nephrectomy. The MCR of calcitriol in these rats with renal failure was significantly lower than in control rats with sham operations. Plasma concentrations of calcitriol did not differ between the rats with moderate renal failure and control rats (sham, 74.7 plusminus 3.6 pg/ml, N = 7; renal failure, 67.7 plusminus 6.0, N = 6; serum creatinine 0.56 plusminus0.02 mg/dl vs. 0.96 plusminus 0.02); however, the levels were significantly lower in rats with severe renal failure (sham, 66.5 plusminus 5.1 pg/ml, N = 7, severe renal failure, 49.6 plusminus 2.1 pg/ml, N = 8; serum creatinine 0.53 plusminus 0.01 mg/dl vs. 1.40 plusminus 0.03). Subcutaneous infusion of calcitriol (1 mug/kg/day) in rats with severe renal failure for one week significantly increased the MCR of calcitriol (0.22 plusminus .01 vs. 0.17 plusminus .01 ml/min/kg, P < 0.001). Infusion of 25(OH)D3 (600 ng/day) or 24,25(OH)2D3 (1 mu-g/day) in rats with renal failure for one week also increased the MCR of calcitriol (25(OH)D3, 0.25 plusminus 0.01 ml/min/kg; 24,25(OH)2D3, 0.25 plusminus 0.01, both p < 0.001) when compared to rats with renal failure infused with vehicle (0.21 plusminus 0.01). Administration of 24,25(OH)2D3 significantly lowered the plasma levels of calcitriol in rats with renal failure (52.3 plusminus 3.1 pg/ml, P < 0.05) in comparison to the rats with renal failure infused with vehicle (67.7 plusminus 6.0). The decreased plasma levels of calcitriol were most likely due to the increase in MCR following infusion of 24,25(OH)2D3. Treatment with 25(OH)D3 also decreased the plasma levels of calcitriol (55.0 plusminus4.3 pg/ml) when compared to the control rats with renal failure, but the decrease was not statistically significant.

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