Combination treatment with tenapanor and sevelamer synergistically reduces urinary phosphorus excretion in rats.

Combination treatment with tenapanor and sevelamer synergistically reduces urinary phosphorus excretion in rats. Am J Physiol Renal Physiol. 2020 Dec 07;: Authors: King AJ, Kohler J, Fung C, Jiang Z, Quach A, Kumaraswamy P, Chertow GM, Rosenbaum DP Abstract The majority of patients with chronic kidney disease (CKD) receiving dialysis do not reach target serum phosphorus concentrations, despite treatment with phosphate binders. Tenapanor is a non-binder, sodium/hydrogen exchanger isoform 3 (NHE3) inhibitor that reduces paracellular intestinal phosphate absorption. This pre-clinical study evaluated the effect of tenapanor and varying doses of sevelamer carbonate on urinary phosphorus excretion, a direct reflection of intestinal phosphate absorption. We measured 24-hour urinary phosphorus excretion in male rats assigned to groups dosed orally with vehicle or tenapanor (0.3 mg/kg/day) and provided a diet containing varying amounts of sevelamer (0-3% w/w). We also evaluated the effect of the addition of tenapanor or vehicle on 24-hour urinary phosphorus excretion to rats on a stable dose of sevelamer (1.5% w/w). When administered together, tenapanor and sevelamer decreased urinary phosphorus excretion significantly more than either tenapanor or sevelamer alone across all sevelamer dose levels. The Bliss statistical model of independence indicated that the combination was synergistic. A stable sevelamer dose (1.5% w/w) reduced mean (±stan...
Source: American Journal of Physiology. Renal Physiology - Category: Physiology Authors: Tags: Am J Physiol Renal Physiol Source Type: research