#827 Effect of tenapanor on serum phosphorus (Pi), creatinine (Cre), and body weight (BW) gain in hemodialysis patients

Abstract Background and Aims Hyperphosphatemia occurs in most patients with advanced chronic kidney disease (CKD) and is associated with several adverse clinical outcomes. Intestinal inhibition of sodium/hydrogen exchanger isoform 3 (NHE3) by Tenapanor (TENAP) has been shown to reduce Pi absorption alongside sodium absorption inhibition, although the mechanism is not entirely elucidated. TENAP was originally developed for the treatment of constipation and not specifically as an intestinal Pi absorption inhibitor, leaving many unknown aspects from a clinical perspective. This study investigates the relationship between the serum Pi-lowering effect of TENAP and the increase in body weight between hemodialysis (HD) sessions, and other parameters. Method In 44 patients on maintenance HD who were able to take TENAP for at least three months and whose drug effects had stabilized, we studied the effects on weight gain and electrolyte changes. Weight gain during the two-day interdialysis period in patients receiving HD three times per week was observed. The effects of TENAP administration on serum Pi, creatinine (Cre), and body weight gain (ΔBW) were measured twice a month. Mean levels of Pi, Cre and ΔBW during the three-month period were compared between the three months before and after TENAP administration. We also evaluated the relationship between the changes in the mean values of the difference before and after treatment for each parameter (ΔPi, ΔCre, ΔBW). Results Most patients took 5 mg of TENAP twice daily before breakfast and dinner to alleviate constipation. In the analysis of the three months before and after TENAP administration, Pi levels significantly decreased in 26 patients, with no significant increase observed. In some patients, the administration of phosphate binders was reduced. After TENAP administration, Cre decreased significantly in 12 patients, and ΔBW decreased significantly in 13 patients. A significant positive correlation was observed between ΔPi and ΔBW (P = 0.024) and between ΔPi and ΔCre (P = 0.013). Conclusion In HD patients, TENAP administration has been confirmed to stably lower serum Pi for a relatively long period. The decrease in Pi and the change in BW by TENAP administration have been suggested to be related to the inhibition of Na absorption by NHE3 in the gastrointestinal tract. It is also suggested that a decrease in Cre may occur in conjunction with a decrease in Pi, although the cause remains unknown.