FACTORS INFLUENCING CALCITRIOL METABOLISM IN RENAL-FAILURE

Metabolic clearance rate (MCR) and production rate (PR) of calcitriol is decreased in experimental renal failure. In this experiment, we studied uremia and secondary hyperparathyroidism as possible causes of the abnormal calcitriol metabolism. Normal rats were made uremic by infusing phosphorus-free urine for 24 hours. Both the MCR (0.22 ± 0.01 ml/min/kg, N = 6 P < 0.001) and the PR (16.6 ± 1.97 ng/kg/day, P < 0.01) of calcitriol were significantly suppressed in normal rats following urine infusion when compared to saline infused rats (MCR, 0.30 ± 0.01; PR, 32.9 ± 4.1, N = 6). Different levels of protein intake by rats with renal failure produced by subtotal nephrectomy also alter the PR but not the MCR of calcitriol. Thus, the synthesis of calcitriol was significantly lower in rats with renal failure fed a high protein (50% protein) diet (17.6 ± 0.7 ng/kg/day, N = 8, P < 0.001) than in rats with renal failure fed a normal protein (20% protein) diet (22.2 ± 1.4,N = 7). Thyroparathyroidectomy (TPTX) did not alter the MCR of calcitriol in renal failure, even though parathyroid hormone, which may suppress the degradation enzyme, could be elevated in this model of renal failure. The MCR of TPTXed rats with renal failure (0.15 ± 0.01 ml/min/kg, N = 7) remained lower than that of the TPTXed control rats (0.19 ± 0.01, N = 7, P < 0.001), and chronic infusion of PTH to TPTXed rats with renal failure did not change the MCR of calcitriol (0.15 ± 0.01, vs. control, 0.24 ± 0.01). We conclude that urine contains factors which inhibit calcitriol metabolism, and secondary hyperparathyroidism is not responsible for the decreased MCR in renal failure.