Calcium Carbonate versus Sevelamer Hydrochloride as Phosphate Binders after Long-Term Disease Progression in 5/6 Nephrectomized Rats

Abstract

Our aim was to compare the effects of calcium carbonate and sevelamer-HCl treatments on calcium-phosphate metabolism and renal function in 5/6 nephrectomized (NX) rats so that long-term disease progression preceded the treatment. After 15-week progression, calcium carbonate (3.0%), sevelamer-HCl (3.0%), or control diets (0.3% calcium) were given for 9 weeks. Subtotal nephrectomy reduced creatinine clearance (−40%), plasma calcidiol (−25%), and calcitriol (−70%) and increased phosphate (+37%), parathyroid hormone (PTH) (11-fold), and fibroblast growth factor-23 (FGF-23) (4-fold). In NX rats, calcium carbonate diet increased plasma (+20%) and urinary calcium (6-fold), reduced plasma phosphate (−50%) and calcidiol (−30%), decreased creatinine clearance (−35%) and FGF 23 (−85%), and suppressed PTH without influencing blood pH. In NX rats, sevelamer-HCl increased urinary calcium (4-fold) and decreased creatinine clearance (−45%), PTH (−75%), blood pH (by 0.20 units), plasma calcidiol (−40%), and calcitriol (−65%). Plasma phosphate and FGF-23 were unchanged. In conclusion, when initiated after long-term progression of experimental renal insufficiency, calcium carbonate diet reduced plasma phosphate and FGF-23 while sevelamer-HCl did not. The former induced hypercalcemia, the latter induced acidosis, while both treatments reduced vitamin D metabolites and deteriorated renal function. Thus, delayed initiation influences the effects of these phosphate binders in remnant kidney rats.