Nephrol Dial Transplant (2001) 16: 1870-1878
© 2001 European Renal Association-European Dialysis and Transplant Association
Sevelamer hydrochloride (Renagel®), a non-calcaemic phosphate binder, arrests parathyroid gland hyperplasia in rats with progressive chronic renal insufficiency
1 Pharmaceutical Development Laboratories, Kirin Brewery Co., Ltd, Takasaki, 2 Fuji Gotenba Research Laboratory, Chugai Pharmaceutical Co., Ltd, Shizuoka, Japan, and 3 GelTex Pharmaceuticals, Inc., Massachusetts, USA
Background. It has been demonstrated that dietary phosphate restriction suppresses parathyroid hormone (PTH) secretion and parathyroid cell proliferation in experimental animals with chronic renal insufficiency (CRI) independently of serum calcium and 1,25(OH)2D3 levels. This study was conducted to examine whether sevelamer hydrochloride (Renagel®; hereafter referred to as sevelamer), a non-calcaemic phosphate binder could inhibit the parathyroid gland (PTG) hyperplasia in rats with progressive CRI.
Methods. Male Sprague–Dawley rats were injected twice with low doses of adriamycin (ADR). Two weeks after the last injection of ADR, rats were fed a diet containing 1 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 of the PTG in paraffin section was calculated using an imaging analyser.
Results. Dietary sevelamer treatment inhibited the elevations of serum phosphorus, calciumxphosphorus product, and PTH levels that occurred as the study progressed. Sevelamer also suppressed maximal PTG area and there existed positive strong correlation between maximal PTG area and serum PTH levels at the end of the study. Serum phosphorus levels positively correlated well with serum PTH levels and maximal PTG area. In contrast, serum calcium or 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 hyperplasia accompanied by the elevation of serum PTH levels. The correlation analysis suggests that reduced serum phosphorus levels contributed to the suppression of PTG hyperplasia and resulted in the reduction of PTH levels in this animal model after the sevelamer treatment. The management of phosphorus control started from early stage of CRI could prevent PTG hyperplasia and facilitate later management of secondary hyperparathyroidism.
Keywords: parathyroid hormone (PTH); parathyroid-gland hyperplasia; phosphate binder; serum phosphorus; sevelamer hydrochloride (Renagel®)
Nobuo Nagano PhD, Pharmaceutical Development Laboratories, Kirin Brewery Co., Ltd, 3 Miyahara-cho, Takasaki-shi, Gunma 370-1295, Japan.
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