ArticleNephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association2021
Evidence of an intestinal phosphate transporter alternative to type IIb sodium-dependent phosphate transporter in rats with chronic kidney disease.
Article in Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 20 citations in OpenAlex.
- Modified-release nicotinamide for the treatment of hyperphosphataemia in haemodialysis patients: 52-week efficacy and safety results of the phase 3 randomized controlled NOPHOS trial.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2023Trial
- Mechanism of reduced intestinal phosphate absorption by tenapanor: a hypothesis.Clinical kidney journal · 2026Review
- Phosphate in Physiological and Pathological Mineralization: Important yet Often Unheeded.MedComm · 2025Review
- Effect of an NHE3 inhibitor in combination with an NPT2b inhibitor on gastrointestinal phosphate absorption in Rodent models.PloS one · 2024Article
- Age quadratically affects intestinal calcium and phosphorus transporter gene expression in broiler chickens.Animal bioscience · 2022Article
- Phosphate intake, hyperphosphatemia, and kidney function.Pflugers Archiv : European journal of physiology · 2022Review
- 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
- Enhanced phosphate absorption in intestinal epithelial cell-specific NHE3 knockout mice.Acta physiologica (Oxford, England) · 2022Article
- 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
- The Complexities of Organ Crosstalk in Phosphate Homeostasis: Time to Put Phosphate Sensing Back in the Limelight.International journal of molecular sciences · 2021Review
- Constitutive depletion of Slc34a2/NaPi-IIb in rats causes perinatal mortality.Scientific reports · 2021Article
- Targeting NaPi-IIb for Hyperphosphatemia in Chronic Kidney Disease Patients - The Dead End?Kidney international reports · 2021Article
- Metformin Attenuates Renal Fibrosis in a Mouse Model of Adenine-Induced Renal Injury Through Inhibiting TGF-β1 Signaling Pathways.Frontiers in cell and developmental biology · 2021Article
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPhosphate is absorbed in the small intestine via passive flow and active transport.NaPi-IIb, a type II sodium-dependent phosphate transporter, is considered to mediate active phosphate transport in rodents. To study the regulation of intestinal phosphate transport in chronic kidney disease (CKD), we analyzed the expression levels of NaPi-IIb, pituitary-specific transcription factor 1 (PiT-1) and PiT-2 and the kinetics of intestinal phosphate transport using two CKD models.
methodsCKD was induced in rats via adenine orThy1 antibody injection. Phosphate uptake by intestinal brush border membrane vesicles (BBMV) and the messenger RNA (mRNA) expression of NaPi-IIb, PiT-1 and PiT-2 were analyzed. The protein expression level of NaPi-IIb was measured by mass spectrometry (e.g. liquid chromatography tandem mass spectrometry).
resultsIn normal rats, phosphate uptake into BBMV consisted of a single saturable component and its Michaelis constant (Km) was comparable to that of NaPi-IIb. The maximum velocity (Vmax) correlated with mRNA and protein levels of NaPi-IIb. In the CKD models, intestinal phosphate uptake consisted of two saturable components. The Vmax of the higher-affinity transport, which is thought to be responsible for NaPi-IIb, significantly decreased and the decrease correlated with reduced NaPi-IIb expression. The Km of the lower-affinity transport was comparable to that of PiT-1 and -2. PiT-1 mRNA expression was much higher than that of PiT-2, suggesting that PiT-1 was mostly responsible for phosphate transport.
conclusionsThis study suggests that the contribution of NaPi-IIb to intestinal phosphate absorption dramatically decreases in rats with CKD and that a low-affinity alternative to NaPi-IIb, in particular PiT-1, is upregulated in a compensatory manner in CKD.
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