The calcemic response to PTH in the rat: Effect of elevated PTH levels and uremia

Bover, Jordi; Jara, Aquiles; Pedro Trinidad; Rodriguez, Mariano; Martin-Malo, Alejandro; Felsenfeld, Arnold J.
August 1994
Kidney International;Aug1994, Vol. 46 Issue 2, p310
Academic Journal
Secondary hyperparathyroidism (2° HPT) is a consistent funding in renal failure. A decreased calcemic response (CR) to parathyroid hormone (PTH) contributes to the development of 2° HPT. Since parathyroidectomy (PTX) corrects the decreased CR to PTH in azotemic animals, down-regulation of PTH receptors induced by an elevation of PTH has been advanced as tin important factor in the development of 2° HPT. The goal of the study was to determine in azotemic rats whether a progressive reduction of PTH improves the CR to PTH and whether the maintenance of normal PTH levels corrects the CR to PTH. Seven groups of pair-fed rats were studied. Three groups of rats had normal renal function (NRF groups) and received either a high phosphorus (HPDNRF), a moderate phosphorus (MPD-NRF), or a low phosphorus (LPDNRF) diet. Three azotemic (NX) groups received similar diets (HPD-NX, MPD-NX and LPD-NX groups) in order to vary the magnitude of 2° HPT. A PTX was performed in a fourth azotemic group (PTX-NX) to induce the complete absence of PTH. After 14 to 16 days on the maintenance diets, the CR to PTH was determined with a 48 hour infusion of 1–34 rat PTH. Serum PTH levels in the NRF groups were 48 ± 4 (HPD-NRF), 40 ± 2 (MPD-NRF) and 35 ± 2 (LPD-NRF) pg/ml and in the NX groups were 327 ± 24 (HPD-NX), 80 ± 6 (MPD-NX) and 49 ± 3 (LPD-NX) pg/ml; scrum PTH levels were greater in the NX groups than the respective NRF dietary control (P < 0.01). The CR to PTH was similar in the three NX groups and the PTX-NX group, and less in each of the three NX groups than the respective dietary control in the NRF groups (P < 0.001). The CR to PTH was similar in the HPD-NX and MPD-NX groups despite an almost fourfold difference in PTH. The PTH level in the LPD-NX group was similar to the PTH level of the HPD-NRF group (49 ± 3 vs. 48 ± 4 pg/ml). Nevertheless, despite similar PTH, phosphorus, and calcitriol levels, the CR to PTH was less in the LPD-NX than the HPD-NRF group (4.1 ± 0.5 vs. 8.3 ± 0.3 mg/dl. P < 0.001. Urinary calcium and phosphorus excretion were similar in all groups and thus could not account for the differences in the CR to PTH. In a second study, the CR to PTH was greater in non-azotemic PTX rats than both azotemic PTX rats and normal rats (P < 0.01). In summary, (1) PTX corrected the CR to PTH in renal failure to the range observed in normal ruts: (2) a significant reduction of PTH levels by dietary manipulation did not improve the CR to PTH; (3) maintenance of normal PTH levels did not correct the CR to PTH; and (4) PTX also improved the CR to PTH in rats with normal renal function. In conclusion, our results suggest that the mechanism by which PTX restores the CR in uremia may include factors other than down-regulation of PTH receptors, and uremia may be an independent factor contributing to the decreased CR to PTH.


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