ORIGINAL RESEARCH article
Front. Physiol.
Sec. Renal Physiology and Pathophysiology
Volume 16 - 2025 | doi: 10.3389/fphys.2025.1684982
This article is part of the Research TopicCardiovascular–Kidney–Metabolic Syndrome: Interorgan Crosstalk, Pathophysiology, and TherapeuticsView all 3 articles
Unbiased kinome profiling identifies key and novel mediators of chronic kidney disease in hyperlipidemic mice
Provisionally accepted
- Institute for Molecular Cardiovascular Research, University Hospital RWTH Aachen, Aachen, Germany
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Chronic kidney disease (CKD) is a progressive condition associated with increased mortality and morbidity, placing a substantial burden on healthcare systems globally. CKD often coexists with cardiovascular disease (CVD), further complicating patient outcomes. This study investigates the kinomic profile of hyperlipidemic mice to understand the signaling mechanisms underlying CKD progression and its cardiovascular consequences. Apoe-/- mice were subjected to a Western-type diet, with or without adenine supplementation to induce CKD. Kinase activity was profiled using PamGene® assays on renal cortex samples collected at early (4 weeks) and late (12 weeks) stages of CKD. It could be demonstrated that CKD led to significant increases in peptide phosphorylation related to both tyrosine and serine-threonine kinases, which were particularly pronounced in the late-stage model. Therefore, the kinase activity in the kidney increased upon CKD development in a CKD-stage-dependent manner. Notably, the activity of cyclin-dependent kinases (CDKs) was reduced at early disease stages but remained unaffected in late stages. Pathway analysis revealed stage-specific alterations in cell cycle regulation, inflammation, oxidative stress, lipid metabolism, and fibrosis pathways associated with kinase activity changes throughout disease progression. These findings highlight critical kinases involved in CKD development and suggest their potential roles in mediating pathological processes such as inflammation and fibrosis. Targeting specific kinases may offer novel therapeutic strategies for mitigating CKD progression and its cardiovascular complications. Future research should explore the causal relationships between newly identified kinases and CKD development.
Keywords: Chronic Kidney Disease, Hyperlipidemia, kinases, Kinomics, Cardiorenal
Received: 13 Aug 2025; Accepted: 15 Sep 2025.
Copyright: © 2025 Bonnin-Marquez, Maas, Corcini-Berndt and Van Der Vorst. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Emiel P.C. Van Der Vorst, evandervorst@ukaachen.de
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