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Tenapanor, an inhibitor of the sodium/hydrogen exchanger 3, has been evaluated previously as a phosphate-lowering therapy for patients with end-stage kidney disease (ESKD). However, its safety and efficacy in reducing serum phosphate and PTH remain controversial. Therefore, we aimed to perform a meta-analysis exploring the effects of Tenapanor in patients with ESKD on dialysis.
We systematically searched Cochrane Library, Embase, and PubMed for randomized-controlled trials (RCTs) comparing Tenapanor versus placebo in patients with ESKD for efficacy and safety outcomes. The search was conducted on June 10, 2023. Statistical analyses were performed using R software 4.3.1. Heterogeneity was assessed with I2 statistics.
We included 944 patients from five RCTs, of whom 588 (62%) were randomized to Tenapanor. Follow-up ranged from 6 to 26 weeks. The intervention group had a mean age range of 55.2-63.4 years. Baseline phosphate levels varied from 7.3-7.67 in the Tenapanor group and 7.2-7.87 in the placebo group. Tenapanor doses ranged from 1 mg bid to 30 mg bid.
Tenapanor significantly reduced serum phosphate (MD -1.09 mg/dL; 95% CI -2.02 to -0.16; P=0.008; I2=95%; Figure 1) and PTH levels (MD -62.61 pg/mL; 95% CI -108.47 to -16.74; P=0.007; I2=0%; Figure 2) as compared with placebo. However, tenapanor significantly increased serum potassium levels (MD 0.18 mmol/L; 95% CI 0.05 to 0.31; P=0.008; I2=0%) and the incidence of diarrhea (RR 3.34; CI 95% 2.39 to 4.65; P<0.001; I2=0%; Figure 3) relative to placebo.
In this meta-analysis of RCTs, Tenapanor reduced phosphate and PTH levels in patients with ESKD when evaluated at a wide range of doses, albeit increasing serum potassium.