#2340 Tenapanor administration combined with phosphate binders provides synergistic phosphate lowering effect

Abstract Background and Aims Excess of phosphate (P) is a risk for mortality in hemodialysis (HD) patients. Previous medications against hyperphosphatemia available were all P binders. For further decrease of serum P, adding medications of same mechanism had been considered. As these drugs act competitively, the attempt would be less effective than expected. Tenapanor has a novel mechanism which reduces serum P via selective inhibition of sodium/proton exchange transporter 3. As synergistic effects are expected on combination of drugs with different mechanisms, we investigated tenapanor effects on serum P, P absorption, and furthermore, we also compared the effect of tenapanor with or without baseline P binders administration. Method 20 patients undergoing HD whom 10mg of tenapanor were started and continued over 3 months without changing the doses of P binders were evaluated on this study. They were performed HD under the condition enable to evaluate intradialytic P removal dose. At the beginning, 44 patients started tenapanor administration. 24 patients were excluded because of stopping administration within 3 months (10 cases), of changing dose of P binders (9 cases), of blood flow rate (Qb) above 250 ml/min (5 cases). Pre and post dialytic blood were sampled at the first HD of the week once a month for 3 months before and after starting tenapanor administration, and pre and post dialytic P and urea nitrogen (UN) and pre dialytic hematocrit were measured. These results were used for calculation of estimated amount of intradialytic P removal as previously reported (Nephrol. Dial. Transp. 2012; 27 suppl.2: SPA546, ii494). We have confirmed that this calculation is accurate when Qb ranges between 150–250 ml/min. We also showed that previous report showed daily amount of P absorption (PA) was calculated as 39.9% of estimated amount of intradialytic P removal in first HD of the week (Nephrol. Dial. Transp. 2015; 30 suppl.3: SP648, iii592). At the start of administration, 7 patients were treated without P binder (tenapanor single use group; Group Si) and 13 patients were already treated with P binders (tenapanor added on P binder group; Group Ad). Six types of P bin ders had been used in Group Ad (sevelamer hydrochloride, bixalomer, calcium carbonate, ferric citrate, sucroferric oxyhydroxide hydrate and lanthanum carbonate hydrate). The potency ratio of these P binders per weight had been reported as 1:1:1.5:1.5:3:3. (Semin Dial 2011;24:41-9, Clin Nephrol 2008;70:404-10. Therapeutic Research 2014; 35:285-91). The changes of pre dialytic serum P concentration (Ppre) and PA after tenapanor administration were evaluated. Decrease of Ppre (ΔPpre) and reduction of PA (ΔPA) were compared between Group Si and Ad. The relationship between the potency of prescribed P binders and ΔPpre or ΔPA was also evaluated. Results Ppre was significantly reduced after starting administration of tenapanor (7.6 ± 1.1 vs 5.9 ± 1.2 mg/dl, p = 4.3 × 10−8). The estimated PA was also significantly reduced (550 ± 102 vs 450 ± 110 mg/day, p = 4.5 × 10−6). However, pre-dialytic UN concentration was not significantly changed, which suggests protein intake in both periods were similar. Compared with Group Si, Group Ad showed increased ΔPpre (1.2 ± 0.6 vs 1.7 ± 0.9, p = 0.027) and ΔPA (55 ± 62 vs 125 ± 65, p = 0.016). In other words, when tenapanor was added on P binders, ΔPA increase was more than twice compared to tenapanor single use (Fig. 1). There was a significant relation between ΔPA and potency of combined P binders (R = 0.455, p = 0.044). Conclusion Oral administration of tenapanor significantly reduced P adsorption and improved serum P level in patients undergoing HD either when it was administrated alone or adding on P binders. This P absorption reduction effect of tenapanor was greatly enhanced when it was added on P binders. The mechanism of this synergistic effect would be an important research question.