Hyperphosphatemia-induced hyperparathyroidism in 5/6 nephrectomized rats: development of a new animal model.

Abstract

BACKGROUND: We require a stable model to understand the molecular mechanism by which isolated hyperphosphatemia induces hyperparathyroidism secondary to chronic renal failure. The present study established a rat model of hyperphosphatemia-induced secondary hyperparathyroidism in chronic renal failure. METHODS: Twenty-nine rats with 5/6 nephrectomy (Nx) were divided into three groups and were fed for 10 weeks on a high phosphate diet (1.2% phosphate) starting from three different post-Nx time points. Parathyroid hormone mRNA in parathyroid gland was measured by real-time PCR and parathyroid cell hyperplasia was tested by proliferating cell nuclear antigen (PCNA) assay. RESULTS: The 10 rats fed a high phosphate diet starting from the fourth week post-Nx had isolated hyperphosphatemia and excess synthesis/secretion of parathyroid hormone, and hyperplasia of the parathyroid glands were induced (r = 0.86 - 0.97, P < 0.001), but the levels of serum calcium and 1, 25 (OH)2D3 did not change. CONCLUSION: A rat model of hyperphosphatemia-induced secondary hyperparathyroidism in chronic renal failure was established by 5/6 Nx and 10 weeks-high phosphate diet starting from the fourth week post-Nx.