Targeting ion channel networks in diabetic kidney disease: from molecular crosstalk to precision therapeutics and clinical innovation

Diabetic kidney disease (DKD), a major microvascular complication of diabetes, is closely associated with functional imbalances in ion channels regulating sodium (Na+), calcium (Ca2+), potassium (K+), and chloride (Cl–). This review systematically examines the roles of ion channels in glomerular fil...

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Main Authors: Wenfeng Wang, Bi Ke, Chen Wang, Xiaojing Xiong, Xiuyuan Feng, Hua Yan
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-06-01
Series:Frontiers in Medicine
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Online Access:https://www.frontiersin.org/articles/10.3389/fmed.2025.1607701/full
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author Wenfeng Wang
Bi Ke
Chen Wang
Xiaojing Xiong
Xiuyuan Feng
Hua Yan
author_facet Wenfeng Wang
Bi Ke
Chen Wang
Xiaojing Xiong
Xiuyuan Feng
Hua Yan
author_sort Wenfeng Wang
collection DOAJ
description Diabetic kidney disease (DKD), a major microvascular complication of diabetes, is closely associated with functional imbalances in ion channels regulating sodium (Na+), calcium (Ca2+), potassium (K+), and chloride (Cl–). This review systematically examines the roles of ion channels in glomerular filtration barrier dysfunction, tubular reabsorption, and fibrotic processes in DKD, with emphasis on the pathological relevance of sodium-glucose cotransporter 2 (SGLT2), epithelial sodium channels (ENaC), transient receptor potential (TRP) channels, chloride channels, aquaporins (AQPs), and PIEZO channels. We further evaluate the clinical efficacy and challenges of ion channel-targeted therapies, including SGLT2 inhibitors and mineralocorticoid receptor antagonists. Emerging strategies integrating ion channel omics, machine learning, engineered biomaterials, and exosome-based delivery systems are proposed to shift DKD treatment paradigms from disease progression delay to pathological reversal. Interdisciplinary collaboration is critical to achieving personalized precision medicine, offering novel perspectives for DKD diagnosis and management.
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publisher Frontiers Media S.A.
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series Frontiers in Medicine
spelling doaj-art-2bfaff70abba4b3797ef8870d5dbef632025-08-20T03:27:47ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2025-06-011210.3389/fmed.2025.16077011607701Targeting ion channel networks in diabetic kidney disease: from molecular crosstalk to precision therapeutics and clinical innovationWenfeng Wang0Bi Ke1Chen Wang2Xiaojing Xiong3Xiuyuan Feng4Hua Yan5Department of Cardiology, Wuhan Asia General Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, Hubei, ChinaDepartment of Cardiology, Ezhou Central Hospital, Ezhou, Hubei, ChinaDepartment of Cardiology, Wuhan Asia General Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, Hubei, ChinaDepartment of Cardiology, Wuhan Asia General Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, Hubei, ChinaDepartment of Cardiology, Ezhou Central Hospital, Ezhou, Hubei, ChinaDepartment of Cardiology, Ezhou Central Hospital, Ezhou, Hubei, ChinaDiabetic kidney disease (DKD), a major microvascular complication of diabetes, is closely associated with functional imbalances in ion channels regulating sodium (Na+), calcium (Ca2+), potassium (K+), and chloride (Cl–). This review systematically examines the roles of ion channels in glomerular filtration barrier dysfunction, tubular reabsorption, and fibrotic processes in DKD, with emphasis on the pathological relevance of sodium-glucose cotransporter 2 (SGLT2), epithelial sodium channels (ENaC), transient receptor potential (TRP) channels, chloride channels, aquaporins (AQPs), and PIEZO channels. We further evaluate the clinical efficacy and challenges of ion channel-targeted therapies, including SGLT2 inhibitors and mineralocorticoid receptor antagonists. Emerging strategies integrating ion channel omics, machine learning, engineered biomaterials, and exosome-based delivery systems are proposed to shift DKD treatment paradigms from disease progression delay to pathological reversal. Interdisciplinary collaboration is critical to achieving personalized precision medicine, offering novel perspectives for DKD diagnosis and management.https://www.frontiersin.org/articles/10.3389/fmed.2025.1607701/fullion channelsdiabetic kidney diseasetargeted therapyprecision medicinesodium-glucose cotransporter 2
spellingShingle Wenfeng Wang
Bi Ke
Chen Wang
Xiaojing Xiong
Xiuyuan Feng
Hua Yan
Targeting ion channel networks in diabetic kidney disease: from molecular crosstalk to precision therapeutics and clinical innovation
Frontiers in Medicine
ion channels
diabetic kidney disease
targeted therapy
precision medicine
sodium-glucose cotransporter 2
title Targeting ion channel networks in diabetic kidney disease: from molecular crosstalk to precision therapeutics and clinical innovation
title_full Targeting ion channel networks in diabetic kidney disease: from molecular crosstalk to precision therapeutics and clinical innovation
title_fullStr Targeting ion channel networks in diabetic kidney disease: from molecular crosstalk to precision therapeutics and clinical innovation
title_full_unstemmed Targeting ion channel networks in diabetic kidney disease: from molecular crosstalk to precision therapeutics and clinical innovation
title_short Targeting ion channel networks in diabetic kidney disease: from molecular crosstalk to precision therapeutics and clinical innovation
title_sort targeting ion channel networks in diabetic kidney disease from molecular crosstalk to precision therapeutics and clinical innovation
topic ion channels
diabetic kidney disease
targeted therapy
precision medicine
sodium-glucose cotransporter 2
url https://www.frontiersin.org/articles/10.3389/fmed.2025.1607701/full
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