The importance of skin autofluorescence parameter in stratification of risk of mortality and cardiovascular events in patients receiving programmed hemodialysis


DOI: https://dx.doi.org/10.18565/therapy.2025.1.125-133

Konovalova D.Yu., Lebedev P.A., Zharkov M.N.

1) Samara State Medical University of the Ministry of Healthcare of Russia; 2) V.D. Seredavin Samara Regional Clinical Hospital
Abstract. The review considers the problem of stratification of risk of mortality and cardiovascular complications in patients receiving programmed hemodialysis. Currently, a number of parameters associated with a negative prognosis have been identified, including skin autofluorescence parameter (SAF) – an accessible method for determining advanced glycation end products (AGEs, glycotoxins) in tissues. The main damaging mechanisms of SAF in relation to the structure and function of the vascular wall and myocardium are described. SAF is determined by a semi-automatic method, regardless of the operator, non-invasively using reader devices which are common abroad. The ability of SAF parameter in comparison with other biomarkers to optimize the determination of cardiovascular risk in patients receiving program hemodialysis is covered. Article actualizes the importance of developing domestic SAF reader devices as a basis for a new technology for cardiovascular diseases stratification in patients having chronic kidney disease. The prospects for using this technique are associated not only with the phenomenon of “metabolic memory” associated with the accumulation of AGEs in the tissues of vital organs and vascular wall, but also with the study of SAF parameter in dynamics, as well as the factors determining it.

Literature


1. GBD Chronic Kidney Disease Collaboration. Global, regional, and national burden of chronic kidney disease, 1990–2017: A systematic analysis for the Global Burden of Disease 2017. Lancet. 2020; 395(10225): 709–33.


https://doi.org/10.1016/S0140-6736(20)30045-3. PMID: 32061315. PMCID: PMC7049905.


2. McQueen R.B., Farahbakhshian S., Bell K.F. et al. Economic burden of comorbid chronic kidney disease and diabetes. J Med Econ. 2017; 20(6): 585–91.


https://doi.org/10.1080/13696998.2017.1288127. PMID: 28128669.


3. Шилов Е.М., Шилова М.М., Румянцева Е.И. с соавт. Нефрологическая служба Российской Федерации 2023: часть 1. Заместительная почечная терапия. Клиническая нефрология. 2024; 16(1): 5–14. (Shilov E.M., Shilova M.M., Rumyantseva E.I. et al. Nephrological service of the Russian Federation 2023: Part I. Renal replacement therapy. Klinicheskaya nefrologiya = Clinical Nephrology. 2024; 16(1): 5–14 (In Russ.)).


https://doi.org/10.18565/nephrology.2024.1.5-14. EDN: DAZGYH.


4. Manns B., Hemmelgarn B., Tonelli M. et al.; for Canadians Seeking Solutions and Innovations to Overcome Chronic Kidney Disease. The cost of care for people with chronic kidney disease. Can J Kidney Health Dis. 2019; 6: 2054358119835521.


https://doi.org/10.1177/2054358119835521. PMID: 31057803. PMCID: PMC6452586.


5. O’Lone E., Viecelli A.K., Craig J.C. et al.; SONG-HD CVD Consensus Workshop Investigators. Establishing core cardiovascular outcome measures for trials in hemodialysis: Report of an international consensus workshop. Am J Kidney Dis. 2020; 76(1): 109–20.


https://doi.org/10.1053/j.ajkd.2020.01.022. PMID: 32414662.


6. Давыдова Н.А., Лебедев П.А., Чернышев А.В. с соавт. Клиническое и прогностическое значение параметра аутофлуоресценции кожи у пациентов с ишемической болезнью сердца и заболеванием периферических артерий. Терапия. 2024; 10(2): 32–40. (Davydova N.A., Lebedev P.A., Chernyshev A.V. et al. Clinical and prognostic value of the skin autofluorescence parameter in coronary heart disease and peripheral arterial disease patients. Terapiya = Therapy. 2024; 10(2): 32–40 (In Russ.)).


https://doi.org/10.18565/therapy.2024.2.32-40. EDN: NMIORV.


7. Salazar J., Navarro C., Ortega Á. et al. Advanced glycation end products: New clinical and molecular perspectives. Int J Environ Res Public Health. 2021; 18(14): 7236.


https://doi.org/10.3390/ijerph18147236. PMID: 34299683. PMCID: PMC8306599.


8. Simm A. Protein glycation during aging and in cardiovascular disease. J Proteomics. 2013; 92: 248–59.


https://doi.org/10.1016/j.jprot.2013.05.012. PMID: 23702329.


9. Yamamoto Y., Doi T., Kato I. et al. Receptor for advanced glycation end products is a promising target of diabetic nephropathy. Ann N Y Acad Sci. 2005; 1043: 562–66.


https://doi.org/10.1196/annals.1333.064. PMID: 16037279.


10. Forbes J.M., Yee L.T.L., Thallas V. et al. Advanced glycation end product interventions reduce diabetes-accelerated atherosclerosis. Diabetes. 2004; 53(7): 1813–23.


https://doi.org/10.2337/diabetes.53.7.1813. PMID: 15220206.


11. Petrica L., Vlad A., Gluhovschi G. et al. Glycated peptides are associated with the variability of endothelial dysfunction in the cerebral vessels and the kidney in type 2 diabetes mellitus patients: A cross-sectional study. J Diabetes Complications. 2015; 29(2): 230–37.


https://doi.org/10.1016/j.jdiacomp.2014.11.014. PMID: 25511877.


12. Kandarakis S.A., Piperi C., Topouzis F., Papavassiliou A.G. Emerging role of advanced glycation-end products (AGEs) in the pathobiology of eye diseases. Prog Retin Eye Res. 2014; 42: 85–102.


https://doi.org/10.1016/j.preteyeres.2014.05.002. PMID: 24905859.


13. Li J., Liu D., Sun L. et al. Advanced glycation end-products and neurodegenerative diseases: Mechanisms and perspective. J Neurol Sci. 2012; 317(1–2): 1–5.


https://doi.org/10.1016/j.jns.2012.02.018. PMID: 22410257.


14. Meerwaldt R., Graaff R., Oomen P.H.N. et al. Simple non-invasive assessment of advanced glycation end product accumulation. Diabetologia. 2004; 47(7): 1324–30.


https://doi.org/10.1007/s00125-004-1451-2. PMID: 15243705.


15. Reddy V.P., Aryal P., Darkwah E.K. Advanced glycation end products in health and disease. Microorganisms. 2022; 10(9): 1848.


https://doi.org/10.3390/ microorganisms10091848. PMID: 36144449. PMCID: PMC9501837.


16. Tessier F.J. The Maillard reaction in the human body. The main discoveries and factors that affect glycation. Pathol Biol (Paris). 2010; 58(3): 214–19.


https://doi.org/10.1016/j.patbio.2009.09.014. PMID: 19896783.


17. Rowan S., Bejarano E., Taylor A. Mechanistic targeting of advanced glycation end-products in age-related diseases. Biochim Biophys Acta Mol Basis Dis. 2018; 1864(12): 3631–43.


https://doi.org/10.1016/j.bbadis.2018.08.036. PMID: 30279139. PMCID: PMC6822271.


18. Xu B., Chibber R., Ruggiero D. et al. Impairment of vascular endothelial nitric oxide synthase activity by advanced glycation end products. FASEB J. 2003; 17(10): 1289–91.


https://doi.org/10.1096/fj.02-0490fje. PMID: 12738813.


19. Hwang S.H., Kim H.Y., Zuo G. et al. Anti-glycation, carbonyl trapping and anti-inflammatory activities of chrysin derivatives. Molecules. 2018; 23(7): 1752.


https://doi.org/10.3390/molecules23071752. PMID: 30018253. PMCID: PMC6099615.


20. Laurent S., Boutouyrie P. Arterial stiffness and hypertension in the elderly. Front Cardiovasc Med. 2020; 7: 544302.


https://doi.org/10.3389/fcvm.2020.544302. PMID: 33330638. PMCID: PMC7673379.


21. Budoff M.J., Alpert B., Chirinos J.A. et al. Clinical applications measuring arterial stiffness: An expert consensus for the application of cardio ankle vascular index. Am J Hypertens. 2022; 35(5): 441–53.


https://doi.org/10.1093/ajh/hpab178. PMID: 34791038. PMCID: PMC9088840.


22. Sakaguchi T., Yan S.F., Yan S.D. et al. Central role of RAGE-dependent neointimal expansion in arterial restenosis. J Clin Invest. 2003; 111(7): 959–72.


https://doi.org/10.1172/jci17115. PMID: 12671045. PMCID: PMC152587.


23. Makita Z., Radoff S., Rayfield E.J. et al. Advanced glycosylation end products in patients with diabetic nephropathy. N Engl J Med. 1991; 325(12): 836–42.


https://doi.org/10.1056/NEJM199109193251202. PMID: 1875967.


24. Maasen K., van Greevenbroek M.M.J., Scheijen J.L.J.M. et al. High dietary glycemic load is associated with higher concentrations of urinary advanced glycation end products: The Cohort on Diabetes and Atherosclerosis Maastricht (CODAM) Study. Am J Clin Nutr. 2019; 110(2): 358–66.


https://doi.org/10.1093/ajcn/nqz119. PMID: 31240298.


25. Solbu M.D., Mjøen G., Mark P.B. et al. Predictors of atherosclerotic events in patient on haemodialysis: Post hoc analyses from the AURORA study. Nephrol Dial Transplant. 2018; 33(1): 102–12.


https://doi.org/10.1093/ndt/gfw360. PMID: 27798199.


26. You X., Huang Y.Y., Wang Y. et al. Prediction model for cardiovascular disease risk in hemodialysis patients. Int Urol Nephrol. 2022; 54(5): 1127–34.


https://doi.org/10.1007/s11255-021-02984-7. PMID: 34487297.


27. Epifânio A.P.S., Balbino K.P., Ribeiro S.M.R. et al. Clinical-nutritional, inflammatory and oxidative stress predictors in hemodialysis mortality: A review. Nutr Hosp. 2018; 35(2): 461–68.


https://doi.org/10.20960/nh.1266. PMID: 29756982.


28. Soleymanian T., Niyazi H., Dehkordi S.N.J. et al. Predictors of clinical outcomes in hemodialysis patients: A multicenter observational study. Iran J Kidney Dis. 2017; 11(3): 229–36. PMID: 28575884.


29. Kitamura H., Yamada S., Hiyamuta H. et al. Serum alkaline phosphatase levels and increased risk of brain hemorrhage in hemodialysis patients: The Q-cohort study. J Atheroscler Thromb. 2022; 29(6): 923–36.


https://doi.org/10.5551/jat.62885. PMID: 34108341. PMCID: PMC9174090.


30. Yang Y., Qin X., Li Y. et al. Relationship between serum uric acid and mortality risk in hemodialysis patients: A multicenter prospective cohort study. Am J Nephrol. 2020; 51(10): 823–32.


https://doi.org/10.1159/000509258. PMID: 33070128.


31. Feldreich T., Nowak C., Fall T. et al. Circulating proteins as predictors of cardiovascular mortality in end-stage renal disease. J Nephrol. 2019; 32(1): 111–19.


https://doi.org/10.1007/s40620-018-0556-5. PMID: 30499038. PMCID: PMC6373380.


32. Bargnoux A.-S, Kuster N., Patrier L. et al. Cardiovascular risk stratification in hemodialysis patients in the era of highly sensitive troponins: Should we choose between hs-troponin I and hs-troponin T? Clin Chem Lab Med. 2016; 54(4): 673–82.


https://doi.org/10.1515/cclm-2015-0071. PMID: 26457775.


33. Song Y.-H., Cai G.-Y., Xiao Y.-F., Chen X.-M. Risk factors for mortality in elderly haemodialysis patients: A systematic review and meta-analysis. BMC Nephrol. 2020; 21(1): 377.


https://doi.org/10.1186/s12882-020-02026-x. PMID: 32867718. PMCID: PMC7457491.


34. Meerwaldt R., Hartog J.W.L., Graaff R. et al. Skin autofluorescence, a measure of cumulative metabolic stress and advanced glycation end products, predicts mortality in hemodialysis patients. J Am Soc Nephrol. 2005; 16(12): 3687–93.


https://doi.org/10.1681/ASN.2005020144. PMID: 16280473.


35. Arsov S., Graaff R., van Oeveren W. et al. Advanced glycation end-products and skin autofluorescence in end-stage renal disease: A review. Clin Chem Lab Med. 2014; 52(1): 11–20.


https://doi.org/10.1515/cclm-2012-0832. PMID: 23612551.


36. Schwedler S.B., Metzger T., Schinzel R., Wanner C. Advanced glycation end products and mortality in hemodialysis patients. Kidney Int. 2002; 62(1): 301–10.


https://doi.org/10.1046/j.1523-1755.2002.00423.x. PMID: 12081592.


37. Viramontes-Hörner D., Selby N.M., Taal M.W. Skin autofluorescence and malnutrition as predictors of mortality in persons receiving dialysis: A prospective cohort study. J Hum Nutr Diet. 2020; 33(6): 852–61.


https://doi.org/10.1111/jhn.12764. PMID: 32383489.


38. Viramontes-Hörner D., Selby N.M., Taal M.W. The association of nutritional factors and skin autofluorescence in persons receiving hemodialysis. J Ren Nutr. 2019; 29(2): 149–55.


https://doi.org/10.1053/j.jrn.2018.07.004. PMID: 30309781.


39. Viramontes-Hörner D., Selby N.M., Taal M.W. Factors associated with change in skin autofluorescence, a measure of advanced glycation end products, in persons receiving dialysis. Kidney Int Rep. 2020; 5(5): 654–62.


https://doi.org/10.1016/j.ekir.2020.02.003. PMID: 32405587. PMCID: PMC7210606.


40. Viramontes-Hörner D., Selby N.M., Taal M.W. Prospective study of change in skin autofluorescence over time and mortality in people receiving hemodialysis. Kidney Int Rep. 2024; 9(7): 2110–16.


https://doi.org/10.1016/j.ekir.2024.03.020. PMID: 39081750. PMCID: PMC1128444.


41. McIntyre N.J. Trend and monitoring of skin autofluorescence in patients receiving hemodialysis. Kidney Int Rep. 2024; 9(8): 2335–36.


https://doi.org/10.1016/j.ekir.2024.06.016. PMID: 39156148. PMCID: PMC11328780.


42. Varikasuvu S.R., Sulekar H., Aloori S., Thangappazham B. The association of non-invasive skin autofluorescence measurements with cardiovascular and all-cause mortality in hemodialysis patients: A meta-analysis. Int Urol Nephrol. 2020; 52(9): 1757–69.


https://doi.org/10.1007/s11255-020-02543-6. PMID: 32661621.


About the Autors


Daria Yu. Konovalova, MD, postgraduate student of the Department of therapy, Institute of Professional Education with a course in functional diagnostics, Samara State Medical University of the Ministry of Healthcare of Russia. Address: 443099, Samara, 89 Chapaevskaya St.
E-mail: snowflake0605@mail.ru
ORCID: https://orcid.org/0009-0002-2964-2675
Petr A. Lebedev, MD, Dr. Sci. (Medicime), professor, head of the Department of therapy of the Institute of professional education with a course in functional diagnostics, Samara State Medical University of the Ministry of Healthcare of Russia. Address: 443099, Samara, 89 Chapaevskaya St.
E-mail: palebedev@yahoo.com
ORCID: https://orcid.org/0000-0003-3501-2354
Mikhail N. Zharkov, MD, transfusiologist of the highest category, head of the Department of blood transfusion, V.D. Seredavin Samara Regional Clinical Hospital, chief specialist of the Ministry of Healthcare of the Samara region. Address: 443095, Samara, 159 Tashkentskaya St.
E-mail: Garkov2000@mail.ru
ORCID: https://orcid.org/0009-0007-9989-1526


Similar Articles


Бионика Медиа