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(R); '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 xphosphorus 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.
D000818:Animals; D001707:Biopsy, Needle; D019587:Dietary Supplements; D004195:Disease Models, Animal; D018450:Disease Progression; D004852:Epoxy Compounds / Q000494:pharmacology*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007150:Immunohistochemistry; D007676:Kidney Failure, Chronic / Q000473:pathology* / Q000517:prevention & control*; D007677:Kidney Function Tests; D008297:Male; D010710:Phosphates / Q000378:metabolism; D011073:Polyamines; D011095:Polyethylenes / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D012307:Risk Factors; D012680:Sensitivity and Specificity; D000069603:Sevelamer
D004852:Epoxy Compounds; D010710:Phosphates; D011073:Polyamines; D011095:Polyethylenes; D000069603:Sevelamer