Reversibility of experimental secondary hyperparathyroidism.

Chronic uremia is associated with secondary hyperparathyroidism (HPT). The purpose of the present investigation was to study the reversibility of secondary HPT after reversal of uremia by an isogenic kidney transplantation in the rat. Secondary HPT was induced in two models: Model A comprised 5/6 nephrectomized rats kept on a standard diet (N = 12; PTH 210 +/- 43 pg/ml; plasma urea 24 +/- 2 mmol/liter; and normal control rats, N = 12; PTH 45 +/- 5 pg/ml; plasma urea 6 +/- 0.2 mmol/liter); and Model B comprised 5/6 nephrectomized rats kept on a high phosphorus diet (N = 12; PTH 769 +/- 157 pg/ml; plasma urea 18 +/- 2 mmol/liter). The parathyroid function was examined by measuring the secretory response of PTH to an acute induction of hypo- and hypercalcemia. Acute hypocalcemia in the hyperphosphatemic uremic rats did not significantly increase serum PTH levels (N = 6, delta Ca2+ -0.56 mmol/liter; maximal PTH 1045 +/- 164 pg/ml; basal PTH 690 +/- 134 pg/ml; NS). During hypercalcemia the PTH levels were significantly higher than in the normal controls (N = 6; minimal PTH 24 +/- 5 pg/ml vs. normal controls 5 +/- 0.2 pg/ml, P < 0.05). After 20 weeks of uremia, the uremia was reversed by the isogenic kidney transplantation. One week after reversal of the uremia the PTH levels became normal in both models A and B (28 +/- 6 and 63 +/- 16 pg/ml, respectively) and the kidney transplanted rats from model B had a normal secretory response of PTH to both hypo- and hypercalcemia. To study whether both parathyroid cell hypertrophy and hyperplasia could be down-regulated, 8 uremic glands (N = 9) or 20 normal glands (N = 6) were implanted into one normal rat. Within two weeks the rats regained normocalcemia and PTH levels remained normal from the third day after the increase of glandular mass. The 20 gland rats all had normal PTH suppressibility in response to calcium (minimal PTH 5 +/- 0.3 pg/ml). In conclusion, experimental severe secondary hyperparathyroidism is reversible very quickly after the reversal of uremia. Hyperphosphatemia in uremia is important for the non-suppressibility of the parathyroid glands to calcium. In non-uremic rats even severe parathyroid hyperplasia can be controlled, resulting in normal plasma PTH and Ca2+ levels and in a normal response to hypercalcemia. Thus, the minimal PTH secretion obtained during the induction of hypercalcemia is not an expression of the parathyroid mass.