Trial reportScience translational medicine2018
Inhibition of sodium/hydrogen exchanger 3 in the gastrointestinal tract by tenapanor reduces paracellular phosphate permeability.
Trial report in Science translational medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06481150 (A Novel Approach for Reducing Hyperoxaluria and Kidney Stone Risk.), which is not on this map. Cited by 87 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Novel Approach for Reducing Hyperoxaluria and Kidney Stone Risk.
Who cites it
87 citing papers in PubMed, 2 syntheses or guidelines pooled it, 154 citations in OpenAlex.
- Efficacy and safety of tenapanor vs placebo in treating CKD patients on dialysis and with hyperphosphatemia: a systematic review and meta-analysis of 2251 patients.International urology and nephrology · 2025Pooled it
- Efficacy and safety of tenapanor in end-stage renal disease patients with hyperphosphatemia: a systematic review and meta-analysis.Renal failure · 2024Pooled it
- Trial
- Tenapanor Improves Abdominal Symptoms Irrespective of Changes in Complete Spontaneous Bowel Movement Frequency in Adults with Irritable Bowel Syndrome with Constipation.Digestive diseases (Basel, Switzerland) · 2025Trial
- Efficacy of tenapanor in managing hyperphosphatemia and constipation in hemodialysis patients: A randomized controlled trial.PloS one · 2025Trial
- Pharmacokinetics, Safety, and Tolerability of Tenapanor in Healthy Chinese and Caucasian Volunteers: A Randomized, Open-Label, Single-Center, Placebo-Controlled Phase 1 Study.International journal of clinical practice · 2024Trial
- Long-term safety and decrease of pill burden by tenapanor therapy: a phase 3 open-label study in hemodialysis patients with hyperphosphatemia.Scientific reports · 2023Trial
- Safety and Efficacy of Tenapanor for Long-term Serum Phosphate Control in Maintenance Dialysis: A 52-Week Randomized Phase 3 Trial (PHREEDOM).Kidney360 · 2021Trial
- EOS789, a broad-spectrum inhibitor of phosphate transport, is safe with an indication of efficacy in a phase 1b randomized crossover trial in hemodialysis patients.Kidney international · 2021Trial
- Therapeutic Effects of Add-On Tenapanor for Hemodialysis Patients with Refractory Hyperphosphatemia.American journal of nephrology · 2021Trial
- Effects of Nicotinamide and Lanthanum Carbonate on Serum Phosphate and Fibroblast Growth Factor-23 in CKD: The COMBINE Trial.Journal of the American Society of Nephrology : JASN · 2019Trial
- Efficacy and Safety of Tenapanor in Patients with Hyperphosphatemia Receiving Maintenance Hemodialysis: A Randomized Phase 3 Trial.Journal of the American Society of Nephrology : JASN · 2019Trial
- Tenapanor Beyond Phosphate: Gut Sodium Transport, Stool Transit Time, and Volume Balance in Dialysis Patients.Hemodialysis international. International Symposium on Home Hemodialysis · 2026Review
- Renoprotective effects of gut NHE3 inhibitor tenapanor in a rat model of unilateral renal ischemia-reperfusion injury with contralateral nephrectomy.Biochemistry and biophysics reports · 2026Article
- Review
- Hypophosphatemic rickets: diagnosis and treatment.Archives of endocrinology and metabolism · 2026Review
- Comparative Effectiveness and Safety of Phosphorus-Lowering Drugs for CKD 3-5 Stages.Kidney medicine · 2026Review
- Analysis of Phosphate Transporters in Peritoneal Cells and Tissues and Their Transport Kinetics In Vitro.International journal of molecular sciences · 2026Article
- Emerging treatments and current strategies for mineral, vascular, and bone disorders in chronic kidney disease.World journal of nephrology · 2026Review
- The Impact of Tenapanor on Serum Phosphate in Adult Dialysis Patients: A Narrative Review.Kidney medicine · 2026Review
27 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
31 authors at 7 institutions in 7 countries.
Funding
Abstract
Hyperphosphatemia is common in patients with chronic kidney disease and is increasingly associated with poor clinical outcomes. Current management of hyperphosphatemia with dietary restriction and oral phosphate binders often proves inadequate. Tenapanor, a minimally absorbed, small-molecule inhibitor of the sodium/hydrogen exchanger isoform 3 (NHE3), acts locally in the gastrointestinal tract to inhibit sodium absorption. Because tenapanor also reduces intestinal phosphate absorption, it may have potential as a therapy for hyperphosphatemia. We investigated the mechanism by which tenapanor reduces gastrointestinal phosphate uptake, using in vivo studies in rodents and translational experiments on human small intestinal stem cell-derived enteroid monolayers to model ion transport physiology. We found that tenapanor produces its effect by modulating tight junctions, which increases transepithelial electrical resistance (TEER) and reduces permeability to phosphate, reducing paracellular phosphate absorption. NHE3-deficient monolayers mimicked the phosphate phenotype of tenapanor treatment, and tenapanor did not affect TEER or phosphate flux in the absence of NHE3. Tenapanor also prevents active transcellular phosphate absorption compensation by decreasing the expression of NaPi2b, the major active intestinal phosphate transporter. In healthy human volunteers, tenapanor (15 mg, given twice daily for 4 days) increased stool phosphorus and decreased urinary phosphorus excretion. We determined that tenapanor reduces intestinal phosphate absorption predominantly through reduction of passive paracellular phosphate flux, an effect mediated exclusively via on-target NHE3 inhibition.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.