Sodium phosphate cotransporter 2a inhibitors: potential therapeutic uses.
Curr Opin Nephrol Hypertens
; 31(5): 486-492, 2022 09 01.
Article
en En
| MEDLINE
| ID: mdl-35894284
ABSTRACT
PURPOSE OF REVIEW 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. RECENT FINDINGS:
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 (10âmgâkg-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.SUMMARY:
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.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Insuficiencia Renal Crónica
/
Proteínas Cotransportadoras de Sodio-Fosfato de Tipo IIa
/
Hiperfosfatemia
/
Calcificación Vascular
Tipo de estudio:
Etiology_studies
/
Prognostic_studies
Idioma:
En
Revista:
Curr Opin Nephrol Hypertens
Asunto de la revista:
ANGIOLOGIA
/
NEFROLOGIA
Año:
2022
Tipo del documento:
Article