Аутофлюоресценция кожи в интегральной оценке клинического и метаболического статуса пациентов с терминальной стадией хронической болезни почек
Аутофлюоресценция кожи в интегральной оценке клинического и метаболического статуса пациентов с терминальной стадией хронической болезни почек
Коновалова Д.Ю., Лебедев П.А., Ушакова О.В., Потякина Е.Е., Корнилин Д.В., Гришанов В.Н., Комарова М.В. Аутофлюоресценция кожи в интегральной оценке клинического и метаболического статуса пациентов с терминальной стадией хронической болезни почек // CardioСоматика. 2024. Т. 15, № 4. С. 329–343. DOI: https://doi.org/10.17816/CS636904
________________________________________________
Konovalova DY, Lebedev PA, Ushakova OV, Potyakina EE, Kornilin DV, Grishanov VN, Komarova MV. Skin autofluorescence as part of the comprehensive assessment of clinical and metabolic status of patients with end-stage chronic kidney disease. CardioSomatics. 2024;15(4):329–343. DOI: https://doi.org/10.17816/CS636904
Аутофлюоресценция кожи в интегральной оценке клинического и метаболического статуса пациентов с терминальной стадией хронической болезни почек
Коновалова Д.Ю., Лебедев П.А., Ушакова О.В., Потякина Е.Е., Корнилин Д.В., Гришанов В.Н., Комарова М.В. Аутофлюоресценция кожи в интегральной оценке клинического и метаболического статуса пациентов с терминальной стадией хронической болезни почек // CardioСоматика. 2024. Т. 15, № 4. С. 329–343. DOI: https://doi.org/10.17816/CS636904
________________________________________________
Konovalova DY, Lebedev PA, Ushakova OV, Potyakina EE, Kornilin DV, Grishanov VN, Komarova MV. Skin autofluorescence as part of the comprehensive assessment of clinical and metabolic status of patients with end-stage chronic kidney disease. CardioSomatics. 2024;15(4):329–343. DOI: https://doi.org/10.17816/CS636904
Обоснование. Хроническая болезнь почек (ХБП) — распространённое заболевание, в терминальной стадии требующее трансплантации почки или диализа, преобладающий вид которого — программный гемодиализ (ПГД). Эти высокозатратные технологии заместительной почечной терапии значительно усовершенствованы в последние десятилетия, однако качество жизни и смертность всё ещё высоки, особенно для пациентов, получающих ПГД. В настоящее время выявлен целый ряд параметров, ассоциированных с негативным прогнозом, среди которых аутофлюоресценция кожи (АФК) — доступный способ определения в тканях конечных продуктов гликирования (гликотоксинов), претендующий на роль интегрального биомаркёра. Цель. Установить взаимосвязь АФК с параметрами клинического, метаболического статуса у пациентов, получающих заместительную почечную терапию. Материалы и методы. Проведено исследование 88 пациентов, получающих ПГД, и 27 реципиентов трансплантированной почки (РТП). В работе использован оригинальный ридер АФК. Результаты. АФК значительно выше у РТП и получающих ПГД. Установлена универсальная выраженная зависимость АФК от возраста и факта курения в группах контроля, ПГД и РТП. Предложены модели детерминантов АФК в каждой изученной группе. АФК связан со степенью нутритивного дефицита (по индексу NRI): r=−0,39, p <0,001; индексом коморбидности Чарлсона: r=0,60, p <0,0001; воспалительной активности по С-реактивному белку: r=0,32, p <0,01 в группе ПГД. Заключение. Предложены модели детерминантов АФК в каждой изученной группе. Также в этой группе установлены высокозначимые прямые коррелятивные связи с параметрами гипертрофии левого желудочка и отрицательные с его фракцией выброса. Эти факты позволяют рассматривать АФК как интегральный параметр ремоделирования сердца и метаболического профиля, прежде всего у пациентов, получающих ПГД, намечая перспективы его оценки как параметра прогноза.
BACKGROUND: Chronic kidney disease (CKD) is a common end-stage disease requiring kidney transplantation or dialysis, which main type is program hemodialysis (PHD). These high-cost technologies of renal replacement therapy have significantly improved over recent decades, but the quality of life remains low and mortality is still high, especially in patients receiving PHD. Currently, a number of parameters associated with poor prognosis have been identified, including skin autofluorescence (SAF), an affordable method to detect glycation end products (glycotoxins) in tissues, which claims to be an integral biomarker. AIM: To assess relationship of SAF with clinical and metabolic status parameters in patients receiving renal replacement therapy. MATERIALS AND METHODS: The study included 88 patients receiving PHD and 27 transplanted kidney recipients (TKR). The measurements were performed using the original SAF reader. RESULTS: SAF was significantly higher in TKR and patients receiving PHD. A universal, pronounced relationship of SAF with age and smoking was found in the control, PHD, and TKR groups. Models of SAF determinants in each studied group were proposed. SAF was associated with malnutrition stages (by NRI; r=−0.39; p <0.001), the Charlson comorbidity index (r=0.60, p <0.0001), and inflammatory activity based on C-reactive protein in the PHD group (r=0.32, p <0.01). CONCLUSION: Models of SAF determinants in each studied group were proposed. Furthermore, highly significant direct correlations with left ventricular hypertrophy and its negative ejection fraction were established in this group. These facts suggest that SAF is an integral parameter of cardiac remodeling and metabolic profile, primarily in patients receiving PHD, which promotes it as a prognostic parameter.
Keywords: skin autofluorescence, program hemodialysis, transplanted kidney recipients
1. Echefu G., Stowe I., Burka S., et al. Pathophysiological concepts and screening of cardiovascular disease in dialysis patients // Front Nephrol. 2023. N 3. P. 1198560. doi: 10.3389/fneph.2023.1198560
2. Tonelli M., Karumanchi S.A., Thadhani R. Epidemiology and mechanisms of uremia-related cardiovascular disease // Circulation. 2016. Vol. 133, N 5. P. 518–536. doi: 10.1161/CIRCULATIONAHA.115.018713
3. Bello A.K., Okpechi I.G., Osman M.A., et al. Epidemiology of haemodialysisoutcomes // Nat Rev Nephrol. 2022. Vol. 18, N 6. P. 378–395. doi: 10.1038/s41581-022-00542-7
4. Devine P.A., Courtney A.E., Maxwell A.P. Cardiovascular risk in renal transplant recipients // Journal of Nephrology. 2019. Vol. 32, N 3. P. 389–399. doi: 10.1007/s40620-018-0549-4
5. Wojtaszek E., Oldakowska-Jedynak U., Kwiatkowska M., et al. Uremic Toxins, Oxidative Stress, Atherosclerosis in Chronic Kidney Disease, and Kidney Transplantation // Oxid Med Cell Longev. 2021. Vol. 2021. P. 6651367. doi: 10.1155/2021/6651367
6. Ryoji Nagai R., Mori T., Yamamoto Y., et al. Signifiance of Advanced Glycation End Products in Aging-Related Disease // JAAM. 2010. Vol. 7, N 10. P. 112–119. doi: 10.3793/jaam.7.112
7. Liakopoulos V., Roumeliotis S., Gorny X., et al. Oxidative Stress in Hemodialysis Patients: A Review of the Literature // Oxid Med Cell Longev. 2017. Vol. 2017. P. 3081856. doi: 10.1155/2017/3081856
8. Dekker M., Zwiers M., Heuvel E.R., et al. Skin Autoflorescence, a Non-Invasive Marker for AGE Accumulation, Is Associated with the Degree of Atherosclerosis // PLoS One. 2013. Vol. 8, N 12. P. e83084. doi: 10.1371/journal.pone.008308
9. Meerwaldt R., Graaff R., Oomen P.H., et al. Simple non-invasive assessment of advanced glycation end product accumulation // Diabetologia. 2004. Vol. 47, N 7. P. 1324–1330. doi: 10.1007/s00125-004-1451-2
10. Mulder D.J., van Haelst P.L., Graaff R., et al. Skin autoflorescence is elevated in acute myocardial infarction and is associated with the one-year incidence of major adverse cardiac events // Netherlands Heart Journal. 2009. Vol. 17, N 4. P. 162–168. doi: 10.1007/BF03086239
11. Reddy V.P., Aryal P., Darkwah E.K. Advanced glucation end proucts in health and disease // Microorganisms. 2022. Vol. 10, N 9. P. 1848. doi:10.3390/microorganisms10091848
12. Dunaev A.V., Dremin V.V., Zherebtsov E.A., et al. Analysis individual variability of parameters of laser florescence diagnostics // Biotechnosphere. 2013. Vol. 2, N 26. Р. 39–47. doi: 10.1016/j.medengphy.2015.03.011
13. Burikov A., Cuadrat R., Polemiti E., et al. Advanced glucation end-products, measured as skin autofluorescence, associate with vascular stiffness in diabetic, pre-diabetic and normoglycemic individuals; a cross–sectional study // Cardiovascular Diabetol. 2021. Vol. 20, N 1. P. 110. doi: 10.1186/s12933-021-01296-5
14. Cavero-Redondo I., Soriano–Cano A., Alvares-Bueno C., et al. Skin autofluorescence-Indicated Advanced Glucation End Products as Predictors of Cardiovascular and All-Cause Mortality in High‑Risk subjects: A Systematic Review and Meta-analysis // Jam Heart Assoc. 2018. Vol. 7, N 18. P. e009833. doi: 10.1161/JAHA.118.009833
15. Rattanasompattikul M., Feroze U., Molnar M.Z., Dukkipati R., et al. Charlson comorbidity score is a strong predictor of mortality in hemodialysis patients // Int Urol Nephrol. 2012. Vol. 44, N 6. P. 1813–1823. doi: 10.1007/s11255-011-0085-9
16. Barge-Caballero E., García-López F., Marzoa-Rivas R., et al. PrognosticValue of the Nutritional Risk Index in Heart Transplant Recipients // Rev Esp Cardiol (Engl Ed). 2017. Vol. 70, N 8. P. 639–645. doi: 10.1016/j.recesp.2016.11.015
17. Kornilin D.V., Grishanov V.N., Cherepanov K.V. Pulse excitation fluorescence meter for diagnostic purposes. Proc. SPIE 10685, Biophotonics: Photonic Solutions for Better Health Care VI, 1068515 (17 May 2018). doi: 10.1117/12.2306588
18. Isami F., West B.J., Nakajima S., Yamagishi S.I. Association of advanced glycation end products, evaluated by skin autofluorescence, with lifestyle habits in a general Japanese population // J Int Med Res. 2018. Vol. 46, N 3. P. 1043–1051. doi: 10.1177/0300060517736914
19. 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. Vol. 33, N 6. P. 852–861. doi: 10.1111/jhn.12764
20. Vareesangthip K., Fan S., Davenport A. Is the measurement of tissue advanced glycosylation products by skin autofluorescence associated with mortality in patients treated by peritoneal dialysis? // J Nephrol. 2023. Vol. 36, N 1. P. 217–224. doi: 10.1007/s40620-022-01415-9
21. Hayward S.J.L., Chesnaye N.C., Hole B., et al. EQUAL investigators. Protein Biomarkers and Major Cardiovascular Events in Older People with Advanced CKD: The European Quality (EQUAL) Study. KidneyMed. 2023. Vol. 6, N 1. P. 100745. doi: 10.1016/j.xkme.2023.100745
22. O'Lone E., Howell M., Viecelli A.K., et al. Identifying critically important cardiovascular outcomes for trials in hemodialysis: an international survey with patients, caregivers and health professionals // Nephrol Dial Transplant. 2020. Vol. 35, N 10. P. 1761–1769. doi: 10.1093/ndt/gfaa008
23. Calviño J., Cigarran S., Gonzalez-Tabares L., et al. Advanced glycation end products (AGEs) estimated by skin autofluorescence are related with cardiovascular risk in renal transplant // PLoS One. 2018. Vol. 13, N 8. P. e0201118. doi: 10.1371/journal.pone.0201118
24. Crowley L.E., Johnson C.P., McIntyre N., et al. Tissue advanced glycation end product deposition after kidney transplantation // Nephron Clin Pract. 2013. Vol. 124, N 1–2. P. 54–59. doi: 10.1159/000355692
25. 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. Vol. 35, N 2. P. 461–468. doi: 10.20960/nh.1266
26. Gopal P., Reynaert N.L., Scheijen J.L., et al. Plasma advanced glycation end-products and skin autofluorescence are increased in COPD // Eur Respir J. 2014. Vol. 43. P. 430–438. doi: 10.1183/09031936.00135312
27. You X., Huang Y.Y., Wang Y., et al. Prediction model for cardiovascular disease risk in hemodialysis patients // Int Urol Nephrol. 2022. Vol. 54, N 5. P. 1127–1134. doi: 10.1007/s11255-021-02984-7
28. Sun J., Axelsson J., Machowska A., et al. Biomarkers of Cardiovascular Disease and Mortality Risk in Patients with Advanced CKD // Clin J Am Soc Nephrol. 2016. Vol. 11, N 7. P. 1163–1172. doi: 10.2215/CJN.10441015
29. De Roij van Zuijdewijn C.L., ter Wee P.M., Chapdelaine I., et al. A Comparison of 8 Nutrition-Related Tests to Predict Mortality in Hemodialysis Patients // J Ren Nutr. 2015. Vol. 25, N 5. P. 412–419. doi: 10.1053/j.jrn.2015.02.005
30. Kanda E., Kato A., Masakane I., KannoY. A new nutritional risk index for predicting mortality in hemodialysis patients: Nationwide cohort study // PLoS One. 2019. Vol. 14, N. 3. P. e0214524. doi: 10.1371/journal.pone.0214524
31. Chen X., Han P., Zhu X., et al. Comparison of three nutritional screening tools for detecting sarcopenia in patients with maintenance hemodialysis // Front Public Health. 2022. Vol. 10. P. 996447. doi: 10.3389/fpubh.2022.996447
32. 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. Vol. 29, N 2. P. 149–155. doi: 10.1053/j.jrn.2018.07.004
33. Shardlow A., Mclntyre N.J., Kolhe N.V., et al. The association of skin autofluorescence with cardiovascular events and all‑cause mortality in persons with chronic kidney disease stage 3: A prospectivecohort study // PLoS Med. 2020. Vol. 17, N 7. P. e1003163. doi: 10.1371/jornal.pmed.1003163
________________________________________________
1. Echefu G, Stowe I, Burka S, et al. Pathophysiological concepts and screening of cardiovascular disease in dialysis patients. Front Nephrol. 2023;3:1198560. doi: 10.3389/fneph.2023.1198560
2. Tonelli M, Karumanchi SA, Thadhani R. Epidemiology and mechanisms of uremia-related cardiovascular disease. Circulation. 2016;133(5):518–536. doi: 10.1161/CIRCULATIONAHA.115.018713
3. Bello AK, Okpechi IG, Osman MA, et al. Epidemiology of haemodialysisoutcomes. Nat Rev Nephrol. 2022;18(6):378–395. doi: 10.1038/s41581-022-00542-7
4. Devine PA, Courtney AE, Maxwell AP. Cardiovascular risk in renal transplant recipients. Journal of Nephrology. 2019;32(3):389–399. doi: 10.1007/s40620-018-0549-4
5. Wojtaszek E, Oldakowska-Jedynak U, Kwiatkowska M, et al. Uremic Toxins, Oxidative Stress, Atherosclerosis in Chronic Kidney Disease, and Kidney Transplantation. Oxid Med Cell Longev. 2021;2021:6651367. doi: 10.1155/2021/6651367
6. Ryoji Nagai R, Mori T, Yamamoto Y, et al. Signifiance of Advanced Glycation End Products in Aging-Related Disease. JAAM. 2010;7(10):112–119. doi: 10.3793/jaam.7.112
7. Liakopoulos V, Roumeliotis S, Gorny X, et al. Oxidative Stress in Hemodialysis Patients: A Review of the Literature. Oxid Med Cell Longev. 2017;2017:3081856. doi: 10.1155/2017/3081856
8. Zwiers M, Heuvel ER, et al. Skin Autoflorescence, a Non‑Invasive Marker for AGE Accumulation, Is Associated with the Degree of Atherosclerosis. PLoS One. 2013;8(12):e83084. doi: 10.1371/journal.pone.008308
9. Meerwaldt R, Graaff R, Oomen PH, et al. Simple non-invasive assessment of advanced glycation end product accumulation. Diabetologia. 2004;47(7):1324–1330. doi: 10.1007/s00125-004-1451-2
10. Mulder DJ, van Haelst PL, Graaff R, et al. Skin autoflorescence is elevated in acute myocardial infarction and is associated with the one-year incidence of major adverse cardiac events. Netherlands Heart Journal. 2009;17(4):162–168. doi: 10.1007/BF03086239
11. Reddy VP, Aryal P, Darkwah EK. Advanced glucation end proucts in health and disease. Microorganisms. 2022;10(9);1848. doi:10.3390/microorganisms10091848
12. Dunaev AV, Dremin VV, Zherebtsov EA, et al. Analysis individual variability of parameters of laser florescence diagnostics. Biotechnosphere. 2013;2(26):39–47. doi: 10.1016/j.medengphy.2015.03.011
13. Burikov A, Cuadrat R, Polemiti E, et al. Advanced glucation end-products, measured as skin autofluorescence, associate with vascular stiffness in diabetic, pre-diabetic and normoglycemic individuals; a cross–sectional study. Cardiovascular Diabetol. 2021;20(1):110. doi: 10.1186/s12933-021-01296-5
14. Cavero-Redondo I, Soriano-Cano A, Alvares-Bueno C, et al. Skin autofluorescence-Indicated Advanced Glucation End Products as Predictors of Cardiovascular and All-Cause Mortality in High-Risk subjects: A Systematic Review and Meta-analysis. Jam Heart Assoc. 2018;7(18):e009833. doi: 10.1161/JAHA.118.009833
15. Rattanasompattikul M, Feroze U, Molnar MZ, Dukkipati R, et al. Charlson comorbidity score is a strong predictor of mortality in hemodialysis patients. IntUrolNephrol. 2012;44(6):1813–1823. doi: 10.1007/s11255-011-0085-9
16. Barge-Caballero E, García-López F, Marzoa-Rivas R, et al. PrognosticValue of the Nutritional Risk Index in Heart Transplant Recipients. Rev Esp Cardiol. (Engl Ed.) 2017;70:639–645. doi: 10.1016/j.recesp.2016.11.015
17. Kornilin DV, Grishanov VN, Cherepanov KV. «Pulse excitation fluorescence meter for diagnostic purposes»; Proceedings SPIE 10685, Biophotonics: Photonic Solutions for Better Health Care VI, 1068515. 2018. doi: 10.1117/12.2306588
18. Isami F, West BJ, Nakajima S, Yamagishi SI. Association of advanced glycation end products, evaluated by skin autofluorescence, with lifestyle habits in a general Japanese population. J Int Med Res. 2018;46(3):1043–1051. doi: 10.1177/0300060517736914
19. Viramontes Hörner D, Selby NM, Taal MW. Skin autofluorescence and malnutrition as predictors of mortality in persons receiving dialysis: a prospective cohort study. J Hum Nutr Diet. 2020;33(6):852–861. doi: 10.1111/jhn.12764
20. Vareesangthip K, Fan S, Davenport A. Is the measurement of tissue advanced glycosylation products by skin autofluorescence associated with mortality in patients treated by peritoneal dialysis? J Nephrol. 2023;36(1):217–224. doi: 10.1007/s40620-022-01415-9
21. Hayward SJL, Chesnaye NC, Hole B, et al. EQUAL investigators. Protein Biomarkers and Major Cardiovascular Events in Older People With Advanced CKD: The European Quality (EQUAL) Study. KidneyMed. 2023;6(1):100745. doi: 10.1016/j.xkme.2023.100745
22. O'Lone E, Howell M, Viecelli AK, et al. Identifying critically important cardiovascular outcomes for trials in hemodialysis: an international survey with patients, caregivers and health professionals. Nephrol Dial Transplant. 2020;35(10):1761–1769. doi: 10.1093/ndt/gfaa008
23. Calviño J, Cigarran S, Gonzalez-Tabares L, et al. Advanced glycation end products (AGEs) estimated by skin autofluorescence are related with cardiovascular risk in renal transplant. PLoS One. 2018;13(8):e0201118. doi: 10.1371/journal.pone.0201118
24. Crowley LE, Johnson CP, McIntyre N, et al. Tissue advanced glycation end product deposition after kidney transplantation. Nephron ClinPract. 2013;124(1–2):54–59. doi: 10.1159/000355692
25. Epifânio APS, Balbino KP, Ribeiro SMR, et al. Clinical-nutritional, inflammatory and oxidative stress predictors in hemodialysis mortality: a review. Nutr Hosp. 2018;35(2):461–468. English. doi: 10.20960/nh.1266
26. Gopal P, Reynaert NL, Scheijen JL, et al. Plasma advanced glycation end-products and skin autofluorescence are increased in COPD. Eur Respir J. 2014;43:430–438. doi: 10.1183/09031936.00135312
27. You X, Huang YY, Wang Y, et al. Prediction model for cardiovascular disease risk in hemodialysis patients. Int Urol Nephrol. 2022;54(5):1127–1134. doi: 10.1007/s11255-021-02984-7
28. Sun J, Axelsson J, Machowska A, et al. Biomarkers of Cardiovascular Disease and Mortality Risk in Patients with Advanced CKD. Clin J Am Soc Nephrol. 2016;11(7):1163–1172. doi: 10.2215/CJN.10441015
29. De Roij van Zuijdewijn CL, ter Wee PM, Chapdelaine I, et al. A Comparison of 8 Nutrition-Related Tests to Predict Mortality in Hemodialysis Patients. J Ren Nutr. 2015;25(5):412–419. doi: 10.1053/j.jrn.2015.02.005
30. Kanda E, Kato A, Masakane I, KannoY. A new nutritional risk index for predicting mortality in hemodialysis patients: Nationwide cohort study. PLoS One. 2019;14(3):e0214524. doi: 10.1371/journal.pone.0214524
31. Chen X, Han P, Zhu X, et al. Comparison of three nutritional screening tools for detecting sarcopenia in patients with maintenance hemodialysis. Front Public Health. 2022;10:996447. doi: 10.3389/fpubh.2022.996447
32. Viramontes Hörner D, Selby NM, Taal MW. The Association of Nutritional Factors and Skin Autofluorescence in Persons Receiving Hemodialysis. J Ren Nutr. 2019;29(2):149–155. doi: 10.1053/j.jrn.2018.07.004
33. Shardlow A, Mclntyre NJ, Kolhe NV, et al. The association of skin autofluorescence with cardiovascular events and all-cause mortality in persons with chronic kidney disease stage 3: A prospective cohort study. PLoS Med. 2020:17(7):e1003163. doi: 10.1371/jornal.pmed.1003163
1Самарский государственный медицинский университет, Самара, Россия; 2Самарская областная клиническая больница им. В.Д. Середавина, Самара, Россия; 3Самарский национальный исследовательский университет им. акад. С.П. Королева, Самара, Россия
*snowflake0605@mail.ru
________________________________________________
Darya Y. Konovalova*1, Petr A. Lebedev1, Olga V. Ushakova2, Elena E. Potyakina2, Dmitriy V. Kornilin3, Vladimir N. Grishanov3, Maria V. Komarova3
1Samara State Medical University, Samara, Russia; 2Samara Regional Clinical Hospital named after V.D. Seredavin, Samara, Russia; 3Samara National Research University n.a. S.P. Korolev, Samara, Russia
*snowflake0605@mail.ru