Updates on renal phosphate transport.

IF 2.2 3区医学 Q3 PERIPHERAL VASCULAR DISEASE

Current Opinion in Nephrology and Hypertension Pub Date : 2025-07-01 Epub Date: 2025-05-13 DOI:10.1097/MNH.0000000000001090

Carsten Alexande Wagner, Daniela Egli-Spichtig, Isabel Rubio-Aliaga

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Abstract

Purpose of review: The kidneys control systemic phosphate balance by regulating phosphate transporters mediating the reabsorption of inorganic phosphate (Pi). At least three different Na + -driven Pi cotransporters are located in the brush border membrane (BBM) of proximal tubule cells, NaPi-IIa (SLC34A1), NaPi-IIc (SLC34A3) and PiT-2 (SLC20A2). This review will discuss novel aspects of their regulation, pharmacology, and genetics.

Recent findings: Renal NaPi transporters are not only acutely regulated by the phosphaturic hormones parathyroid hormone (PTH) and Fibroblast Growth Factor 23 (FGF23) but possibly also by further mechanisms. A role of inositol hexakisphosphate (IP6) kinases has been found and their deletion from kidneys causes hypophosphatemia, hyperphosphaturia, and bone demineralization. Inhibitors of NaPis elicit phosphaturia and may reduce levels of PTH and FGF23 in chronic kidney disease (CKD) models. The relevance of renal NaPi transporters is highlighted by loss-of-function mutations in SLC34 transporters and analysis of patients provides new insights into diseases caused by variants. Major manifestations include nephrocalcinosis and -lithiasis, rickets, and variants may predispose to an accelerated decline in kidney function.

Summary: Renal Pi transporters are regulated, may provide novel drug targets for prevention or treatment of hyperphosphatemia, and contribute to the genetic risk to develop kidney stones and CKD.

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肾磷转运的最新进展。

综述目的：肾脏通过调节磷酸盐转运体介导无机磷酸盐（Pi）的重吸收来控制全身磷酸盐平衡。至少有三种不同的Na+驱动Pi共转运蛋白位于近端小管细胞的刷状边界膜（BBM）， NaPi-IIa (SLC34A1), NaPi-IIc （SLC34A3）和PiT-2 （SLC20A2）。本文将讨论其调控、药理学和遗传学的新方面。近期发现：肾NaPi转运蛋白不仅受到磷酸化激素甲状旁腺激素（PTH）和成纤维细胞生长因子23 （FGF23）的急性调节，还可能受到其他机制的影响。己磷酸肌醇（IP6）激酶的作用已被发现，它们在肾脏中的缺失会导致低磷血症、高磷尿症和骨脱矿。在慢性肾脏疾病（CKD）模型中，NaPis抑制剂可引起磷酸尿并可能降低PTH和FGF23的水平。SLC34转运体的功能缺失突变突出了肾NaPi转运体的相关性，对患者的分析为变异引起的疾病提供了新的见解。主要表现为肾钙质沉着症、结石症、佝偻病，其变异可能导致肾功能加速下降。摘要：肾Pi转运蛋白受到调控，可能为预防或治疗高磷血症提供新的药物靶点，并参与肾结石和CKD的遗传风险。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Current Opinion in Nephrology and Hypertension 医学-泌尿学与肾脏学

CiteScore

5.70

自引率

6.20%

发文量

132

审稿时长

6-12 weeks

期刊介绍： A reader-friendly resource, Current Opinion in Nephrology and Hypertension provides an up-to-date account of the most important advances in the field of nephrology and hypertension. Each issue contains either two or three sections delivering a diverse and comprehensive coverage of all the key issues, including pathophysiology of hypertension, circulation and hemodynamics, and clinical nephrology. Current Opinion in Nephrology and Hypertension is an indispensable journal for the busy clinician, researcher or student.