Sevelamer hydrochloride, a phosphate binder, protects against deterioration of renal function in rats with progressive chronic renal insufficiency

Background. Dietary phosphate restriction prevents renal function deterioration in animal models. This study examined whether sevelamer hydrochloride (Renagel®; 'sevelamer' hereafter), a non-calcaemic phosphate binder could slow deterioration of renal function in rats with progressive renal insufficiency. Methods. Wistar Kyoto male rats were singly injected with normal rabbit serum or rabbit anti-rat glomerular basement membrane serum. Three days later, rats were fed a powder diet containing 0, 1 or 3% sevelamer for 58 days. Time course changes of serum levels of blood urea nitrogen (BUN), creatinine, calcium, phosphorus and parathyroid hormone (PTH) were measured throughout, and creatinine clearance (CCr), kidney calcium content and renal histology examined at the end of the study. Results. Sevelamer partially inhibited elevation of BUN and serum creatinine, and completely inhibited increases in serum phosphorus, PTH and calcium x phosphorus product. Sevelamer significantly prevented the decrease in CCr and kidney calcium content elevation. Kidney calcium content and BUN and serum creatinine were strongly positively correlated, and kidney calcium content and CCr strongly negatively correlated. Kidney calcium content correlated well with serum phosphorus, serum calcium x phosphorus product and PTH, but not serum calcium. Sevelamer treatment partly prevented histological deterioration of both glomerular and tubulointerstitial lesions of the kidney. Conclusions. The results suggest that sevelamer protects against renal function deterioration by maintaining kidney calcium at a low level as a result of reducing serum phosphorus and PTH.