ArticleKidney international reports2018
NPT-IIb Inhibition Does Not Improve Hyperphosphatemia in CKD.
Article in Kidney international reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 63 citations in OpenAlex.
- 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
- Review
- Elevated phosphate levels in CKD - a direct threat for the heart.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2025Review
- Hyperphosphatemia in Kidney Failure: Pathophysiology, Challenges, and Critical Role of Phosphorus Management.Nutrients · 2025Review
- A Pan-Inhibitor of Phosphate Transporters AP306 in Hemodialysis Patients.Kidney international reports · 2025Article
- Gut microbiome dynamics of patients on dialysis: implications for complications and treatment.Frontiers in pharmacology · 2025Review
- Phosphate in Cardiovascular Disease: From New Insights Into Molecular Mechanisms to Clinical Implications.Arteriosclerosis, thrombosis, and vascular biology · 2024Review
- Effects of the novel sodium-dependent phosphate cotransporter 2b inhibitor DZ1462 on hyperphosphatemia in chronic kidney disease.American journal of translational research · 2024Article
- Pharmacology of Mammalian NaHandbook of experimental pharmacology · 2024Article
- Effect of an NHE3 inhibitor in combination with an NPT2b inhibitor on gastrointestinal phosphate absorption in Rodent models.PloS one · 2024Article
- Hyperphosphatemia in Chronic Kidney Disease: The Search for New Treatment Paradigms and the Role of Tenapanor.International journal of nephrology and renovascular disease · 2024Review
- Effects of pharmacological inhibition of the sodium-dependent phosphate cotransporter 2b (NPT2b) on intestinal phosphate absorption in mouse and rat models.Pharmacology research & perspectives · 2022Article
- Npt2a as a target for treating hyperphosphatemia.Biochemical Society transactions · 2022Review
- Dose-Response of Tenapanor in Patients With Hyperphosphatemia Undergoing Hemodialysis in Japan-A Phase 2 Randomized Trial.Kidney international reports · 2022Article
- Enhanced phosphate absorption in intestinal epithelial cell-specific NHE3 knockout mice.Acta physiologica (Oxford, England) · 2022Article
- Phosphate Frustration: Treatment Options to Complement Current Therapies.International journal of nephrology · 2022Review
- Phosphate Balance and CKD-Mineral Bone Disease.Kidney international reports · 2021Review
- Intestinal phosphorus absorption: recent findings in translational and clinical research.Current opinion in nephrology and hypertension · 2021Review
- Targeting NaPi-IIb for Hyperphosphatemia in Chronic Kidney Disease Patients - The Dead End?Kidney international reports · 2021Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionSerum phosphate levels are insufficiently controlled in many patients with end-stage renal disease (ESRD), and novel therapeutic strategies are needed. Blocking intestinal phosphate absorption mediated by sodium-dependent phosphate co-transporter type 2b (NPT-IIb) holds promise; thus, we evaluated the efficacy, safety, tolerability, and pharmacokinetics of the novel and specific small molecule NPT-IIb inhibitor ASP3325 for the first time in humans.
methodsWe conducted a randomized, double-blind, placebo-controlled, phase 1a single (n = 88) and multiple (n = 36) ascending dose study in healthy subjects, and a randomized, open-label, uncontrolled, phase 1b study in hyperphosphatemic ESRD patients on hemodialysis (single oral dose, n = 5; multiple oral doses, n = 17). Primary efficacy measures were urinary phosphate and fecal phosphorous excretion (healthy subjects) and serum phosphate level (ESRD patients).
resultsNo time- or dose-dependent changes in urinary phosphate or fecal phosphorous excretion were observed following single/multiple ASP3325 doses for 7 days in healthy subjects. In ESRD patients, ASP3325 administered 3 times daily for 2 weeks before or after a meal did not reduce serum phosphate levels. ASP3325 was safe and well tolerated in both populations.
conclusionNPT-IIb inhibition with ASP3325 was not effective in reducing serum phosphate levels in ESRD patients. The relevance of NPT-IIb in humans and feasibility of oral NPT-IIb inhibitors for treatment of hyperphosphatemia in ESRD remain uncertain.
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Registered trials
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