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AGEs-RAGE Axis and Mitochondrial-Derived Peptides in Advanced Chronic Kidney Disease: Interconnected Pathways Beyond Inflammation and Nutrition

A study · Antioxidants (Basel, Switzerland) · Aug 27, 2026

What this means

Background. Chronic kidney disease [CKD] is characterized by increased glycoxidative stress, inflammation, and mitochondrial dysfunction.

A plain-English summary is on its way. Until then, this is the start of the authors' own summary.

Tested inNot stated
Who it was tested in
Not stated
Kind of research
A study

The science

Original title
AGEs-RAGE Axis and Mitochondrial-Derived Peptides in Advanced Chronic Kidney Disease: Interconnected Pathways Beyond Inflammation and Nutrition.
Authors
Suliman ME, Rahman A, Qureshi AR et al.
Journal
Antioxidants (Basel, Switzerland)
Published
Aug 27, 2026
Study type
Study

Abstract

Background. Chronic kidney disease [CKD] is characterized by increased glycoxidative stress, inflammation, and mitochondrial dysfunction. Advanced glycation end-products [AGEs] and their receptor [RAGE] mediate glycoxidative stress, whereas mitochondrial-derived peptides [MDPs], including humanin [HN], MOTS-c, and humanin-like 1 [HN-L1], regulate mitochondrial stress responses. We investigated links between AGE-RAGE activation and mitochondrial signaling in CKD. Methods. Serum AGEs, soluble RAGE isoforms, and MDPs were measured by ELISA in 160 adults with kidney failure undergoing living-donor kidney transplantation and in 80 controls, Results. CKD patients showed higher AGEs and esRAGE, lower AGEs/sRAGE ratios, and reduced MDPs. AGEs correlated positively with sRAGE, cRAGE, and HN, while MOTS-c was inversely associated with AGEs and the AGEs/sRAGE ratio. In multivariable analyses, HN remained independently associated with AGEs, sRAGE, and the AGEs/sRAGE ratio, whereas MOTS-c showed an inverse association with the AGEs/sRAGE ratio. CRP was associated with the AGEs/sRAGE ratio while PEW showed no associations with AGEs-RAGE components or MDP. Conclusions. CKD is characterized by increased glycoxidative stress and reduced MDPs, reflecting altered mitochondrial stress signaling. AGEs-RAGE and MDPs are biologically linked, suggesting partially overlapping but distinct pathophysiological pathways.

Read it on PubMed ↗

Suliman ME, Rahman A, Qureshi AR et al. AGEs-RAGE Axis and Mitochondrial-Derived Peptides in Advanced Chronic Kidney Disease: Interconnected Pathways Beyond Inflammation and Nutrition. Antioxidants (Basel, Switzerland). 2026. doi:10.3390/antiox15080956. PMID: 42650220. https://pubmed.ncbi.nlm.nih.gov/42650220/

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