Factors in the development of secondary hyperparathyroidism during graded renal failure in the rat

Factors in the development of secondary hyperparathyroidism during graded renal failure in the rat. Secondary hyperparathyroidism (2° HPT) develops as a result of renal failure. Hypocalcemia, phosphorus retention, calcitriol deficiency and skeletal resistance to the calcemic action of parathyroid hormone (PTH) are closely interrelated pathogenic factors important for the development of 2° HPT in renal failure. Since previous studies have mainly focused on advanced renal failure, only limited data are available in early renal failure. The goal of the present study was to evaluate how alterations in the dietary calcium and phosphorus composition affect the factors known to contribute to the genesis of 2° HPT in early and more advanced renal failure. To achieve this goal, graded differences in renal function were surgically induced in 453 rats while the dietary content of calcium and phosphorus was varied. Three different diets were used: (1) a high phosphorus diet (HPD), to induce phosphorus retention and stimulate 2° HPT; (2) a high calcium diet (HCaD), to inhibit calcitriol synthesis; and (3) a moderate calcium-moderate phosphorus diet (MCaPD), to separate the effects of high dietary phosphorus and calcium. Based on the serum creatinine (S Cr ) concentration rats were assigned to one of four different groups: (1) normal renal function (S Cr ≤ 0.3 mg/dl); (2) mild renal failure (S Cr 0.4 to 0.6 mg/dl); (3) moderate renal failure (S Cr 0.7 to 0.8 mg/dl); or (4) advanced renal failure (S Cr ≥ 0.9 mg/dl). As the severity of renal failure increased, progressive 2° HPT developed in each of the dietary groups. In the HPD group, the increase in PTH in normals from 47 ± 2 to 135 ± 14 pg/ml in mild renal failure (P