Decoding diabetic kidney disease: a comprehensive review of interconnected pathways, molecular mediators, and therapeutic insights

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14310%2F25%3A00141448" target="_blank" >RIV/00216224:14310/25:00141448 - isvavai.cz</a>

Result on the web

<a href="https://doi.org/10.1186/s13098-025-01726-4" target="_blank" >https://doi.org/10.1186/s13098-025-01726-4</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1186/s13098-025-01726-4" target="_blank" >10.1186/s13098-025-01726-4</a>

Result language

angličtina

Original language name

Decoding diabetic kidney disease: a comprehensive review of interconnected pathways, molecular mediators, and therapeutic insights

Original language description

Background Diabetic kidney disease (DKD) is a chronic kidney condition that arises from prolonged hyperglycaemia that can progress to kidney failure, severe morbidity, and mortality if left untreated. It is the major cause of chronic kidney disease among people who have diabetes, accounting for a significant percentage of patients with end-stage kidney disease who require kidney replacement therapy. Main body In DKD, numerous dysbalanced metabolic, haemodynamic, inflammatory signalling pathways, and molecular mediators interconnect, creating a feedback loop that promotes general kidney damage. Hyperglycaemia is the primary trigger for DKD and leads gradually to oxidative stress, inflammation, extracellular matrix deposition and fibrosis, glomerular hypertension, and intrarenal hypoxia. Key interconnected metabolic pathways are the hyperglycaemia-mediated polyol, hexosamine, protein kinase C, and advanced glycation end-products pathway hyperactivity. Concurrently, hyperglycaemia-induced renin-angiotensin-aldosterone system stimulation, alters the kidney intraglomerular haemodynamic leading to inflammation through Toll-like receptors, Janus kinase/signal transducer and activator of transcription, and nuclear factor-kappa B, transforming growth factor-beta-mediated excessive extracellular matrix accumulation and fibrosis. The resulting death signals trigger apoptosis and autophagy through Hippo, Notch, and Wnt/beta-catenin pathway activation and microRNA dysregulation. These signals synergistically remodel the kidneys culminating in intrarenal hypoxia, podocyte dysfunction, hyperfiltration, epithelial-mesenchymal transition, and loss of kidney function. The resulting renal failure further upregulates these death pathways and mediators, giving rise to a vicious cycle that further worsens DKD. Conclusion This review provides an overview of the primary molecular mediators and signalling pathways leading to DKD; their interconnectivity at the onset and during DKD progression, the central role of transforming growth factor-beta via different pathways, the Hippo pathway kidney-specific response to hyperglycaemia, and how all mediators and transduction signals result in a vicious circle that exacerbates renal failure. The review gives therapeutic sights to these pathways as druggable targets for DKD management. Understanding these molecular events underlying the pathogenesis of DKD can bridge basic research and clinical application, facilitating the development of innovative management strategies.

Czech name

—

Czech description

—

Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10608 - Biochemistry and molecular biology

Project

—

Continuities

S - Specificky vyzkum na vysokych skolach

Publication year

2025

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Diabetology and Metabolic Syndrome

ISSN

1758-5996

e-ISSN

1758-5996

Volume of the periodical

17

Issue of the periodical within the volume

1

Country of publishing house

GB - UNITED KINGDOM

Number of pages

18

Pages from-to

192

UT code for WoS article

001502179300001

EID of the result in the Scopus database

2-s2.0-105007251366