AGE, RAGE and Diabetic Nephropathy

2010 ◽  
Vol 8 (2) ◽  
pp. 84
Author(s):  
MaÏté Daroux ◽  
Nicolas Grossin ◽  
Eric Boulanger ◽  
◽  
◽  
...  

Diabetes is a disease that is present worldwide and which is associated with a large number of potential complications including chronic kidney disease (CKD). Several factors have been implicated in the development of the latter, including advanced glycation end-products (AGEs), which are formed from the interaction between sugar and proteins. AGE toxicity may be triggered via different mechanisms, especially by receptor binding. Immunohistochemical studies have demonstrated the presence of AGEs in all renal structures (vessels, glomeruli, tubules and the interstitium). They appear to be involved in the exacerbation of renal injury observed during diabetic nephropathy. At present, no specific treatment is yet available, although several therapeutic approaches are under development.

2012 ◽  
Vol 08 (02) ◽  
pp. 98 ◽  
Author(s):  
Maïté Daroux ◽  
Nicolas Grossin ◽  
Eric Boulanger ◽  
◽  
◽  
...  

Diabetes is a disease that is present worldwide and which is associated with a large number of potential complications including chronic kidney disease (CKD). Several factors have been implicated in the development of the latter, including advanced glycation end-products (AGEs), which are formed from the interaction between sugar and proteins. AGE toxicity may be triggered via different mechanisms, especially by receptor binding. Immunohistochemical studies have demonstrated the presence of AGEs in all renal structures (vessels, glomeruli, tubules, and the interstitium). They appear to be involved in the exacerbation of renal injury observed during diabetic nephropathy. At present, no specific treatment is yet available, although several therapeutic approaches are under development.


2013 ◽  
Vol 123 (11) ◽  
pp. 609-616
Author(s):  
Paweł Stróżecki ◽  
Robert Kurowski ◽  
Mariusz Flisiński ◽  
Anna Stefańska ◽  
Grażyna Odrowąż‑Sypniewska ◽  
...  

2016 ◽  
Vol 26 (5) ◽  
pp. 308-314 ◽  
Author(s):  
Hanieh-Sadat Ejtahed ◽  
Pooneh Angoorani ◽  
Golaleh Asghari ◽  
Parvin Mirmiran ◽  
Fereidoun Azizi

2019 ◽  
Vol 34 (12) ◽  
pp. 2018-2030 ◽  
Author(s):  
Karim Belmokhtar ◽  
Jeremy Ortillon ◽  
Stéphane Jaisson ◽  
Ziad A Massy ◽  
Camille Boulagnon Rombi ◽  
...  

Abstract Background Chronic kidney disease (CKD) is associated with increased cardiovascular mortality, frequent vascular calcification (VC) and accumulation of uraemic toxins. Advanced glycation end products and S100 proteins interact with the receptor for advanced glycation end products (RAGE). In the present work, we aimed to investigate the role(s) of RAGE in the CKD–VC process. Methods Apoe−/− or Apoe−/−Ager (RAGE)−/− male mice were assigned to CKD or sham-operated groups. A high-phosphate diet was given to a subgroup of Apoe−/−and Apoe−/−Ager−/− CKD mice. Primary cultures of Ager+/+ and Ager−/− vascular smooth muscle cells (VSMCs) were established and stimulated with either vehicle, inorganic phosphate (Pi) or RAGE ligands (S100A12; 20 µM). Results After 12 weeks of CKD we observed a significant increase in RAGE ligand (AGE and S100 proteins) concentrations in the serum of CKD Apoe−/− mice. Ager messenger RNA (mRNA) levels were 4-fold higher in CKD vessels of Apoe−/− mice. CKD Apoe−/− but not CKD Apoe−/− or Ager−/− mice displayed a marked increase in the VC surface area. Similar trends were found in the high-phosphate diet condition. mRNA levels of Runx2 significantly increased in the Apoe−/− CKD group. In vitro, stimulation of Ager+/+VSMCs with Pi or S100A12 induced mineralization and osteoblast transformation, and this was inhibited by phosphonoformic acid (Pi co-transporters inhibitor) and Ager deletion. In vivo and in vitro RAGE was necessary for regulation of the expression of Pit-1, at least in part through production of reactive oxygen species. Conclusion RAGE, through the modulation of Pit-1 expression, is a key molecule in the genesis of VC.


2020 ◽  
Vol 112 (1) ◽  
pp. 129-137 ◽  
Author(s):  
Jinluan Chen ◽  
Komal Waqas ◽  
Robby Carlo Tan ◽  
Trudy Voortman ◽  
M Arfan Ikram ◽  
...  

ABSTRACT Background Advanced glycation end products (AGEs) accumulate in tissues with age and in conditions such as diabetes mellitus and chronic kidney disease (CKD), and they may be involved in age-related diseases. Skin AGEs measured as skin autofluorescence (SAF) are a noninvasive reflection of long-term AGE accumulation in tissues. Whether AGEs present in the diet (dAGEs) contribute to tissue AGEs is unclear. Objectives Our aim was to investigate the association between dietary and skin AGEs in the Rotterdam Study, a population-based cohort of mainly European ancestry. Methods In 2515 participants, intake of 3 dAGEs [carboxymethyl-lysine (CML), N-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MGH1), and carboxyethyl-lysine (CEL)] was estimated using FFQs and the content of AGEs measured in commonly consumed foods. SAF was measured 5 y (median value) later using an AGE Reader. The association of dAGEs with SAF was analyzed in linear regression models and stratified for diabetes and chronic kidney disease (CKD, defined as estimated glomerular filtration rate ≤60 mL/min) status. Results Mean ± SD intake was 3.40 ±0.89 mg/d for CML, 28.98 ±7.87 mg/d for MGH1, and 3.11 ±0.89 mg/d for CEL. None of them was associated with SAF in the total study population. However, in stratified analyses, CML was positively associated with SAF after excluding both individuals with diabetes and individuals with CKD: 1 SD higher daily CML intake was associated with a 0.03 (95% CI: 0.009, 0.05) arbitrary units higher SAF. MGH1 and CEL intake were not significantly associated with SAF. Nevertheless, the associations were stronger when the time difference between dAGEs and SAF measurements was shorter. Conclusions Higher dietary CML intake was associated with higher SAF only among participants with neither diabetes nor CKD, which may be explained by high AGE formation in diabetes and decreased excretion in CKD or by dietary modifications in these disease groups. The dAGE–SAF associations were also modified by the time difference between measurements. Our results suggest that dAGEs can influence tissue AGE accumulation and possibly thereby age-related diseases. This trial was registered at the Netherlands National Trial Register as NTR6831 (http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=6831) and at the WHO International Clinical Trials Registry Platform as NTR6831 (http://www.who.int/ictrp/network/primary/en/).


Renal Failure ◽  
2011 ◽  
Vol 33 (2) ◽  
pp. 131-137 ◽  
Author(s):  
Markéta Kratochvilová ◽  
Oskar Zakiyanov ◽  
Marta Kalousová ◽  
Vítězslav Kříha ◽  
Tomáš Zima ◽  
...  

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