Sodium phosphate cotransporter 2a inhibitors: potential therapeutic uses.
Animals
Calcium
/ metabolism
Fibroblast Growth Factors
/ metabolism
Humans
Hyperphosphatemia
/ drug therapy
Parathyroid Hormone
/ metabolism
Phosphates
/ metabolism
Renal Insufficiency, Chronic
/ complications
Sodium-Phosphate Cotransporter Proteins, Type IIa
/ antagonists & inhibitors
Vascular Calcification
Journal
Current opinion in nephrology and hypertension
ISSN: 1473-6543
Titre abrégé: Curr Opin Nephrol Hypertens
Pays: England
ID NLM: 9303753
Informations de publication
Date de publication:
01 09 2022
01 09 2022
Historique:
entrez:
27
7
2022
pubmed:
28
7
2022
medline:
29
7
2022
Statut:
ppublish
Résumé
Targeting sodium phosphate cotransporter 2a (Npt2a) offers a novel strategy for treating hyperphosphatemia in chronic kidney disease (CKD). Here we review recent studies on the efficacy of Npt2a inhibition, its plasma phosphate (Pi)-lowering effects, as well as potential "off-target" beneficial effects on cardiovascular consequences. Two novel Npt2a-selective inhibitors (PF-06869206 and BAY-767) have been developed. Pharmacological Npt2a inhibition shows a significant phosphaturic effect and consequently lowers plasma Pi and parathyroid hormone (PTH) levels regardless of CKD. However, plasma fibroblast growth factor 23 (FGF23), a master regulator of Pi homeostasis, shows inconsistent responses between these two inhibitors (no effect by PF-06869206 vs. reduction by BAY-767). In addition to the effects on Pi homeostasis, Npt2a inhibition also enhances urinary excretions of Na+, Cl-, and Ca2+, which is recapitulated in animal models with reduced kidney function. The effect of Npt2a inhibition by BAY-767 on vascular calcification has been studied, with positive results showing that oral treatment with BAY-767 (10 mg kg-1) attenuated the increases in plasma Pi and Ca2+ content in the aorta under the setting of vascular calcification induced by a pan-FGF receptor inhibitor. Together, Npt2a inhibition offers a promising therapeutic approach for treating hyperphosphatemia and reducing cardiovascular complications in CKD. Npt2a inhibition significantly increases urinary Pi excretion and lowers plasma Pi and PTH levels; moreover, it exerts pleiotropic "off-target" effects, providing a novel treatment for hyperphosphatemia and exhibiting beneficial potential for cardiovascular complications in CKD.
Identifiants
pubmed: 35894284
doi: 10.1097/MNH.0000000000000828
pii: 00041552-202209000-00014
pmc: PMC9387751
mid: NIHMS1822694
doi:
Substances chimiques
Parathyroid Hormone
0
Phosphates
0
Sodium-Phosphate Cotransporter Proteins, Type IIa
0
Fibroblast Growth Factors
62031-54-3
Calcium
SY7Q814VUP
Types de publication
Journal Article
Review
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
486-492Subventions
Organisme : BLRD VA
ID : I01 BX004968
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK110621
Pays : United States
Informations de copyright
Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.
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