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Review

The Apelinergic System in Kidney Disease: Novel Perspectives

by
Sara Saladich-Cavallé
1,
Sara Núñez-Delgado
1,2,
Linhui Huo
1,
Frederic Pons-Pellicer
1,
Irene Martínez-Díaz
1,
Conxita Jacobs-Cachá
3,
Sheila Bermejo
1,2,
Jordi Vilardell-Vilà
1,* and
Maria José Soler
1,2,*
1
Nephrology and Transplantation Research Group, Vall d’Hebrón Research Institute (VHIR), Vall d’Hebron University Hospital, Vall d’Hebron Barcelona Hospital Campus, 08035 Barcelona, Spain
2
Nephrology Department, Vall d’Hebron University Hospital, Vall d’Hebron Barcelona Hospital Campus, 08035 Barcelona, Spain
3
Clinical Biochemistry, Drug Delivery and Therapy Research Group, Vall d’Hebrón Research Institute (VHIR), Vall d’Hebron University Hospital, Vall d’Hebron Barcelona Hospital Campus, 08035 Barcelona, Spain
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2026, 27(1), 111; https://doi.org/10.3390/ijms27010111
Submission received: 3 September 2025 / Revised: 6 November 2025 / Accepted: 7 November 2025 / Published: 22 December 2025
(This article belongs to the Special Issue Advances in Understanding Molecular Mechanisms Involved in Chronic Kidney Injury and Repair)
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Abstract

Chronic kidney disease (CKD) is a major complication of diabetes, affecting approximately 30–40% of patients. In many cases, CKD progresses to end-stage renal disease (ESRD). The peptide apelin and its receptor, APLNR, which is expressed in the endothelial cells of renal blood vessels, play a key role in glucose uptake and the regulation of vasodilation in the afferent and efferent glomerular arterioles. Numerous studies have demonstrated that the apelinergic system is dysregulated in various pathologies, including CKD in people with diabetes. In recent years, the apelinergic system has emerged as a promising therapeutic target for several diseases, with various apelin analogs and inhibitors being developed. In this review, we summarize the most recent literature on apelin and its cellular mechanisms of action, highlighting the role of the apelinergic system in various pathologies and its impact on patients with CKD and diabetes. Additionally, we explore the currently available analogs and inhibitors and discuss their potential therapeutic applications.
Keywords: apelin; APLNR; chronic kidney disease (CKD); CKD in persons with diabetes; renin–angiotensin–aldosterone system (RAS) apelin; APLNR; chronic kidney disease (CKD); CKD in persons with diabetes; renin–angiotensin–aldosterone system (RAS)

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MDPI and ACS Style

Saladich-Cavallé, S.; Núñez-Delgado, S.; Huo, L.; Pons-Pellicer, F.; Martínez-Díaz, I.; Jacobs-Cachá, C.; Bermejo, S.; Vilardell-Vilà, J.; Soler, M.J. The Apelinergic System in Kidney Disease: Novel Perspectives. Int. J. Mol. Sci. 2026, 27, 111. https://doi.org/10.3390/ijms27010111

AMA Style

Saladich-Cavallé S, Núñez-Delgado S, Huo L, Pons-Pellicer F, Martínez-Díaz I, Jacobs-Cachá C, Bermejo S, Vilardell-Vilà J, Soler MJ. The Apelinergic System in Kidney Disease: Novel Perspectives. International Journal of Molecular Sciences. 2026; 27(1):111. https://doi.org/10.3390/ijms27010111

Chicago/Turabian Style

Saladich-Cavallé, Sara, Sara Núñez-Delgado, Linhui Huo, Frederic Pons-Pellicer, Irene Martínez-Díaz, Conxita Jacobs-Cachá, Sheila Bermejo, Jordi Vilardell-Vilà, and Maria José Soler. 2026. "The Apelinergic System in Kidney Disease: Novel Perspectives" International Journal of Molecular Sciences 27, no. 1: 111. https://doi.org/10.3390/ijms27010111

APA Style

Saladich-Cavallé, S., Núñez-Delgado, S., Huo, L., Pons-Pellicer, F., Martínez-Díaz, I., Jacobs-Cachá, C., Bermejo, S., Vilardell-Vilà, J., & Soler, M. J. (2026). The Apelinergic System in Kidney Disease: Novel Perspectives. International Journal of Molecular Sciences, 27(1), 111. https://doi.org/10.3390/ijms27010111

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