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

Suliman ME, Rahman A, Qureshi AR, Barany P, Stenvinkel P, Kublickiene K, Lindholm B

Antioxidants (Basel, Switzerland)30 Jul 2026

PMID42650220PMCIDPMC13510039DOI10.3390/antiox15080956PepBankPUB-42650220

Summary

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.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study7

No result from this study comes from a test of the peptide.

Natural levels measured5

These results measure the body's own peptide. Nobody was given the peptide. They are not evidence about taking it. They are left out of key results, evidence counts and charts.

01HumanEndogenous levelObservational studyOther
In adults with kidney failure, serum mitochondrial-derived peptides, a group that includes humanin, were reduced compared with controls.
In plain wordsIn adults with kidney failure, a group of the body's own mitochondrial peptides, which includes humanin, was lower than in controls.
Peptide
Humanin
Outcome
DecreaseSerum mitochondrial-derived peptides (including humanin) in CKD
Study
n = 240
Comparator
Controls
Outcome group
Endogenous peptide levels · Kidney and urinary
Source sentences
Summary
CKD patients showed higher AGEs and esRAGE, lower AGEs/sRAGE ratios, and reduced MDPs.
2 context sentences(design, population, supporting numbers)
Summary · context
whereas mitochondrial-derived peptides [MDPs], including humanin [HN], MOTS-c, and humanin-like 1 [HN-L1], regulate mitochondrial stress responses.
Summary · context
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.
This result measures the body's own Humanin. Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-4265022005
02HumanEndogenous levelObservational studyOther
In adults with kidney failure and controls, serum AGEs correlated positively with humanin.
In plain wordsIn adults with kidney failure, higher advanced glycation products were linked to higher natural humanin levels.
Peptide
Humanin
Outcome
Not applicableCorrelation of AGEs with humanin
Study
n = 240
Outcome group
Endogenous peptide levels · Kidney and urinary
Source sentences
Summary
AGEs correlated positively with sRAGE, cRAGE, and HN
1 context sentence(design, population, supporting numbers)
Summary · context
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.
This result measures the body's own Humanin. Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-4265022006
03HumanEndogenous levelObservational studyOther
In multivariable analyses, humanin remained independently associated with AGEs, sRAGE and the AGEs/sRAGE ratio.
In plain wordsIn adults with kidney failure, natural humanin levels stayed linked to AGEs, sRAGE and their ratio after adjustment.
Peptide
Humanin
Outcome
Not applicableIndependent association of humanin with AGEs, sRAGE and AGEs/sRAGE ratio
Study
n = 240
Outcome group
Endogenous peptide levels · Kidney and urinary
Source sentences
Summary
In multivariable analyses, HN remained independently associated with AGEs, sRAGE, and the AGEs/sRAGE ratio,
1 context sentence(design, population, supporting numbers)
Summary · context
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.
This result measures the body's own Humanin. Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-4265022007
04HumanEndogenous levelObservational studyOther
In adults with kidney failure and controls, serum MOTS‑c was inversely associated with AGEs and with the AGEs/sRAGE ratio.
In plain wordsIn adults with kidney failure and controls, the body's own MOTS‑c was linked to lower AGEs and a lower AGEs/sRAGE ratio.
Peptide
MOTS-c
Outcome
Not applicableAssociation of MOTS-c with AGEs and AGEs/sRAGE ratio
Study
n: not reported in source
Outcome group
Mitochondrial function · Kidney and urinary
Source sentences
Summary
MOTS-c was inversely associated with AGEs and the AGEs/sRAGE ratio.
1 context sentence(design, population, supporting numbers)
Summary · context
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.
This result measures the body's own MOTS-c. Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-4265022002
05HumanEndogenous levelObservational studyOther
In multivariable analyses, serum MOTS‑c showed an inverse association with the AGEs/sRAGE ratio.
In plain wordsAfter adjustment, the body's own MOTS‑c was linked to a lower AGEs/sRAGE ratio.
Peptide
MOTS-c
Outcome
Not applicableAdjusted association of MOTS-c with AGEs/sRAGE ratio
Study
n: not reported in source
Outcome group
Mitochondrial function · Kidney and urinary
Source sentences
Summary
whereas MOTS-c showed an inverse association with the AGEs/sRAGE ratio.
1 context sentence(design, population, supporting numbers)
Summary · context
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.
This result measures the body's own MOTS-c. Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-4265022003

Studies that did not test the peptide alone2

In this study, MOTS-c was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking MOTS-c.

06HumanNot a test of MOTS-c aloneObservational studyOther
In adults with kidney failure, serum mitochondrial-derived peptides (a group that includes MOTS‑c) were reduced compared with controls.
In plain wordsIn adults with kidney failure, the body's own mitochondrial-derived peptides, a group that includes MOTS‑c, were lower than in controls.
Peptide
MOTS-c
Outcome
DecreaseSerum mitochondrial-derived peptide levels in CKD
Study
n = 240
Comparator
Controls
Outcome group
Mitochondrial function · Kidney and urinary
Source sentences
Summary
CKD patients showed higher AGEs and esRAGE, lower AGEs/sRAGE ratios, and reduced MDPs.
1 context sentence(design, population, supporting numbers)
Summary · context
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.
In this study, MOTS-c was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking MOTS-c.
Show in the study text Report a problemFND-4265022001
07HumanNot a test of MOTS-c aloneObservational studyOther
Protein-energy wasting showed no association with AGEs-RAGE components or with mitochondrial-derived peptides (including MOTS‑c).
In plain wordsProtein-energy wasting was not linked to the body's own mitochondrial-derived peptides, a group that includes MOTS‑c.
Peptide
MOTS-c
Outcome
No significant changeAssociation of mitochondrial-derived peptides with protein-energy wasting
Study
n: not reported in source
Outcome group
Aging markers · Whole body
Source sentences
Summary
PEW showed no associations with AGEs-RAGE components or MDP.
1 context sentence(design, population, supporting numbers)
Summary · context
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.
In this study, MOTS-c was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking MOTS-c.
Show in the study text Report a problemFND-4265022004

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Versions 4 to 18Current
28 Oct 2026, 02:02 UTC
The same notice was added 15 times, first on 13 Oct 2026, 21:44 UTC. The status did not change between them.
Study results updated
Version 3
13 Oct 2026, 16:31 UTC
Study data updated · source update from Europe PMC
Version 2
10 Oct 2026, 08:19 UTC
Study results updated
Version 1
9 Oct 2026, 02:47 UTC
First added · source update from Europe PMC