ArticleThe Journal of clinical investigation2020
Selective pharmacological inhibition of the sodium-dependent phosphate cotransporter NPT2a promotes phosphate excretion.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 38 citations in OpenAlex.
- Renal Phosphate Reabsorption in Humans Depends on at Least Three Distinct Transporters Unlike in Mice.Acta physiologica (Oxford, England) · 2026Article
- TMEM174 Deficiency Reduces Longevity by Promoting Phosphate-Driven Vascular Calcification.Research square · 2026Article
- TMEM174 Deficiency Reduces Longevity by Promoting Phosphate-Driven Vascular Calcification.bioRxiv : the preprint server for biology · 2026Article
- The effects of elevated phosphate on the kidney - damaging the gatekeeper.Pflugers Archiv : European journal of physiology · 2026Review
- The Pathogenic Roles of Local Vitamin D Metabolism Defect in Valve Inflammation and Calcification.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Characterisation of phosphate transport in epididymis and prostate with possible relevance for semen quality.EBioMedicine · 2025Article
- A key role of ATAmerican journal of physiology. Renal physiology · 2025Article
- Updates on renal phosphate transport.Current opinion in nephrology and hypertension · 2025Review
- Phosphate in Physiological and Pathological Mineralization: Important yet Often Unheeded.MedComm · 2025Review
- Carcinogenesis Associated with Toxin Nephropathy: Proposed Mediation by Phosphate Toxicity.Cells · 2025Review
- Beyond SGLT2: proximal tubule transporters as potential drug targets for chronic kidney disease.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2025Review
- Biology of the proximal tubule in body homeostasis and kidney disease.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2025Review
- Vitamin DScientific reports · 2024Article
- Exploring endocrine FGFs - structures, functions and biomedical applications.International journal of biochemistry and molecular biology · 2024Review
- Pharmacology of Mammalian NaHandbook of experimental pharmacology · 2024Article
- Kidney glycolysis serves as a mammalian phosphate sensor that maintains phosphate homeostasis.The Journal of clinical investigation · 2023Article
- Phosphate induces inflammation and exacerbates injury from cigarette smoke in the bronchial epithelium.Scientific reports · 2023Article
- Regulation of FGF23 production and phosphate metabolism by bone-kidney interactions.Nature reviews. Nephrology · 2023Review
- Physiopathology of Phosphate Disorders.Advances in kidney disease and health · 2023Review
- Increased PHOSPHO1 expression mediates cortical bone mineral density in renal osteodystrophy.The Journal of endocrinology · 2022Article
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8 authors at 2 institutions in 1 country.
Funding
Abstract
The sodium-phosphate cotransporter NPT2a plays a key role in the reabsorption of filtered phosphate in proximal renal tubules, thereby critically contributing to phosphate homeostasis. Inadequate urinary phosphate excretion can lead to severe hyperphosphatemia as in tumoral calcinosis and chronic kidney disease (CKD). Pharmacological inhibition of NPT2a may therefore represent an attractive approach for treating hyperphosphatemic conditions. The NPT2a-selective small-molecule inhibitor PF-06869206 was previously shown to reduce phosphate uptake in human proximal tubular cells in vitro. Here, we investigated the acute and chronic effects of the inhibitor in rodents and report that administration of PF-06869206 was well tolerated and elicited a dose-dependent increase in fractional phosphate excretion. This phosphaturic effect lowered plasma phosphate levels in WT mice and in rats with CKD due to subtotal nephrectomy. PF-06869206 had no effect on Npt2a-null mice, but promoted phosphate excretion and reduced phosphate levels in normophophatemic mice lacking Npt2c and in hyperphosphatemic mice lacking Fgf23 or Galnt3. In CKD rats, once-daily administration of PF-06869206 for 8 weeks induced an unabated acute phosphaturic and hypophosphatemic effect, but had no statistically significant effect on FGF23 or PTH levels. Selective pharmacological inhibition of NPT2a thus holds promise as a therapeutic option for genetic and acquired hyperphosphatemic disorders.
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