Sevelamer hydrochloride, a calcium-free phosphate binder, inhibits parathyroid cell proliferation in partially nephrectomized rats.

Background. Secondary hyperparathyroidism characterized by hyperplasia of the parathyroid gland (PTG) is a consequence of chronic renal insufficiency (CRI). Dietary phosphate restriction and sevelamer hydrochloride, a calcium-free phosphate binder, suppress parathyroid hormone (PTH) secretion and PTG hyperplasia in experimental animals with CRI, independently of serum calcium and 1,25(OH) 2 D 3 concentrations. In the present study, the effect of sevelamer on PTG cell proliferation in rats with CRI was investigated. Methods. Seven weeks after a 5/6 nephrectomy, rats were fed a diet containing 0, 1 or 3% sevelamer for 4 weeks, and sham-operated rats were fed a normal diet. Serum calcium, phosphorus, PTH and 1,25(OH) 2 D 3 concentrations were measured. The number of cells positive for proliferating cell nuclear antigen (PCNA) in the maximal two-dimensional PTG area was counted at the end of study. Results. Sevelamer inhibited increases in serum phosphorus, calcium-phosphorus product and PTH concentrations without affecting serum calcium or 1,25(OH) 2 D 3 . Sevelamer also suppressed the maximal PTG area and PCNA-positive cells. There was also a strong correlation between the maximal PTG area and serum PTH concentration, and between PCNA-positive cells and the maximal PTG area, as well as between serum phosphorus concentration and PCNA-positive cells. Conclusions. These results indicate that sevelamer treatment reduces serum phosphorus concentration and could inhibit PTG cell proliferation and prevent PTG hyperplasia.