Renal mineral handling in normal rats treated with sevelamer hydrochloride(Renagel((R))), a noncalcemic phosphate binder

The effects of sevelamer hydrochloride (Renagel (R); hereafter referred to as sevelamer), a noncalcemic phosphate binder, on renal mineral handling we re examined in rats. Normal rats were fed a diet containing 0.3, 1, 3, and 5% sevelamer for 8 days, and serum, urine, and the immunohistochemical loca lization of the type II Na/Pi cotransporter protein in the kidney were anal yzed. Rats treated with 3 or 5% sevelamer showed significant decreases in s erum phosphorus (P) and parathyroid hormone (PTH) levels, with no changes i n serum calcium (Cal, magnesium (Mg), or 1,25(OH)(2)D-3 levels. Increases w ere observed in urinary excretions of Ca and Mg associated with a reduction in the PTH level in rats treated with 3 or 5% sevelamer. Rats treated with 1% or higher concentrations of sevelamer showed significant dose-dependent and marked reductions of the urinary P excretion, and the tubular reabsorp tion of P was maximized to almost 100% in the 5% sevelamer group. The hypop hosphaturia in rats treated with 3 or 5% sevelamer was accounted for by the reductions in serum PTH and P per se, and immunohistochemical analysis sho wed that the expression of type II Na/Pi cotransporter protein was markedly increased at the brush border membranes of the deep and superficial nephro ns in rats treated with 5% sevelamer as compared with rats given a normal d iet. In conclusion, sevelamer rapidly lowered serum P and PTH levels in nor mal rats. Sevelamer treatment also produced a marked hypophosphaturia assoc iated with translocation of type II Na/Pi cotransporter protein and increas ed urinary Ca and Mg excretions by the reduction of PTH. Copyright (C) 2001 S. Karger AG, Basel.