Sevelamer hydrochloride (Renagel (R)), a non-calcaemic phosphate binder, arrests parathyroid gland hyperplasia in rats with progressive chronic renalinsufficiency

Background. It has been demonstrated that dietary phosphate restriction sup presses parathyroid hormone (PTH) secretion and parathyroid cell proliferat ion in experimental animals with chronic renal insufficiency (CRI) independ ently of serum calcium and 1,25(OH)(2)D-3 levels. This study was conducted to examine whether sevelamer hydrochloride (Renagel (R); hereafter referred to as sevelamer), a non-calcaemic phosphate binder could inhibit the parat hyroid gland (PTG) hyperplasia in rats with progressive CRI. Methods. Male Sprague-Dawley rats were injected twice with low doses of adr iamycin (ADR). Two weeks after the last injection of ADR, rats were fed a d iet containing I or 3% sevelamer for 84 days. Time course changes of serum levels of calcium, phosphorus, and PTH were measured. At the end of study, serum 1,25(OH)2D3 levels were measured and the maximal two-dimension area o f the PTG in paraffin section was calculated using an imaging analyser. Results. Dietary sevelamer treatment inhibited the elevations of serum phos phorus, calcium x phosphorus product, and PTH levels that occurred as the s tudy progressed. Sevelamer also suppressed maximal PTG area and there exist ed positive strong correlation between maximal PTG area and serum PTH level s at the end of the study. Serum phosphorus levels positively correlated we ll with serum PTH levels and maximal PTG area. In contrast, serum calcium o r 1,25(OH)2D3 levels did not show any correlation with serum PTH levels and maximal PTG area. Conclusions. Sevelamer treatment arrested hyperphosphataemia and PTG hyperp lasia accompanied by the elevation of serum PTH levels. The correlation ana lysis suggests that reduced serum phosphorus levels contributed to the supp ression of PTG hyperplasia and resulted in the reduction of PTH levels in t his animal model after the sevelamer treatment. The management of phosphoru s control started from early stage of CRI could prevent PTG hyperplasia and facilitate later management of secondary hyperparathyroidism.