Genotoxic biomarkers in patients on hemodialiasis

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It is generally recognized that genotoxic damage have essential etiopathogenetic significance, and its prevention is an important measure to preserve human life and health. In the framework of this concept, literature information on studies of genotoxic biomarkers in patients with various hemodialysis regiments has been reviewed and summarized, and ways to prevent detectable genotoxicity have been identified. Based on the analysis of the known data, it was concluded that patients of this group have an increased level of DNA and chromosome damage in peripheral blood lymphocytes. Based on the results of individual studies, it was shown that one of the strategies for reducing genotoxicity may be the improvement of hemodialysis therapy methods and regimes, as well as pharmacological and nutritional correction of genotoxic effects.

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About the authors

Natalia V. Eremina

Zakusov Research Institute of Pharmacology

Author for correspondence.
ORCID iD: 0000-0002-7226-5505
SPIN-code: 5224-1968

Russian Federation, Moscow

Cand. Sci. (Biol.) Senior Research Associate of Laboratory of Drug Toxicology

Andrey D. Durnev

Zakusov Research Institute of Pharmacology

ORCID iD: 0000-0003-0218-8580
SPIN-code: 8426-0380
Scopus Author ID: 7006060753
ResearcherId: S-7428-2016

Russian Federation, Moscow

Dr. Sci. (Med.), Professor, Corresponding Member of RAS


  1. Webster AC, Nagler EV, Morton RL, Masson P. Chronic Kidney Disease. Lancet. 2017; 389(10075):1238-1252.
  2. Capitanio U, Bensalah K, Bex A, et al. Epidemiology of Renal Cell Carcinoma. Eur Urol. 2019;75(1):74-84.
  3. Сигитова ОН. Хроническая болезнь почек и хроническая почечная недостаточность: современные подходы к терминологии, классификации и диагностике // Вестник современной клинической медицины. 2008. – Т. 1. – № 1. – С. 83–87. [Sigitova OH. Chronic kidney disease and chronic renal failure: current approaches to terminology, classification and diagnosis. Bulletin of modern clinical medicine. 2008;1(1):83-87 (In Russ.)].
  4. Zhang X, Lerman LO. The metabolic syndrome and chronic kidney disease. Transl Res. 2017;183: 14-25.
  5. Kawada T. Association between metabolic syndrome and chronic kidney disease. Clin Chim Acta. 2018;478:44.
  6. Kittiskulnam P, Thokanit NS, Katavetin P, et al. The magnitude of obesity and metabolic syndrome among diabetic chronic kidney disease population: A nationwide study. PLoS One. 2018;13(5): e0196332.
  7. Himmelfarb J, Ikizler TA. Hemodialysis. N Engl J Med. 2010;363(19):1833-1845.
  8. Абдикаликова ТЖ, Мурсалова ЖШ. Характеристика пациентов с хронической болезнью почек, находящихся на заместительной почечной терапии, в зависимости от степени коморбидности // Кардиоваскулярная терапия и профилактика. – 2019. – Т. 18. № S1. – С. 3. [Abdikalikova TZh, Mursalova ZhSh. Characterization of patients with chronic kidney disease undergoing renal replacement therapy, depending on the degree of comorbidity. Cardiovascular therapy and prevention. 2019;18(S1):3 (In Russ.)].
  9. Jha V, Garcia-Garcia G, Iseki K, et al. Chronic kidney disease: global dimension and perspectives. Lancet. 2013;382(9888):260-272.
  10. Fraser SDS, Roderick PJ. Kidney disease in the Global Burden of Disease Study 2017. Nat Rev Nephrol. 2019;15(4):193-194.
  11. Xie Y, Bowe B, Mokdad AH, et al. Analysis of the Global Burden of Disease study highlights the global, regional, and national trends of chronic kidney disease epidemiology from 1990 to 2016. Kidney Int. 2018;94(3):567-581.
  12. Андрусев А.М., Перегудова Н.Г., Шинкарев М.Б., Томилина Н.А. Заместительная терапия терминальной хронической почечной недостаточности в Российской Федерации 2014–2018 гг. Краткий отчет по данным Общероссийского Регистра заместительной почечной терапии Российского диализного общества. – О.О.О.Н. «Российское Диализное Общество», 2019. – 19 с. [Andrusev AM, Peregudova NG, Shinkarev MB, Tomilina NA. Zamestitel’naya terapiya terminal’noy khronicheskoy pochechnoy nedostatochnosti v Rossiyskoy Federatsii 2014–2018 gg. Kratkiy otchet po dannym Obshcherossiyskogo Registra zamestitel’noy pochechnoy terapii Rossiyskogo dializnogo obshchestva. O.O.O.N. “Rossiyskoye Dializnoye Obshchestvo”; 2019. 19 р. (In Russ.)]. Доступно по:–2018_short.PDF. Ссылка активна на 15.05.2020.
  13. Lowrance WT, Ordoñez J, Udaltsova N, Russo P, Go AS. CKD and the risk of incident cancer. J Am Soc Nephrol. 2014;25(10):2327-2334.
  14. Tu H, Wen CP, Tsai SP, et al. Cancer risk associated with chronic diseases and disease markers: prospective cohort study. BMJ. 2018;360: k134.
  15. Maisonneuve P, Agodoa L, Gellert R, et al. Cancer in patients on dialysis for end-stage renal disease: an international collaborative study. Lancet. 1999;354(9173):93-99. 10.1016/s0140-6736(99)06154-1.
  16. Park S, Lee S, Kim Y, et al. Risk of cancer in pre-dialysis chronic kidney disease: A nationwide population-based study with a matched control group. Kidney Res Clin Pract. 2019;38(1):60-70.
  17. McKenna DJ, McKeown SR, McKelvey-Martin VJ. Potential use of the comet assay in the clinical management of cancer. Mutagenesis. 2008;23(3):183-190.
  18. Migliore L, Coppedè F, Fenech M, Thomas P. Association of micronucleus frequency with neurodegenerative diseases. Mutagenesis. 2011; 26(1):85-92.
  19. Fenech M. The cytokinesis-block micronucleus technique and its application to genotoxicity studies in human populations. Environ Health Perspect. 1993;101(Suppl 3):101-107.
  20. Collins AR. The comet assay for DNA damage and repair: principles, applications, and limitations. Mol Biotechnol. 2004;26(3):249-261.
  21. Dhawan A, Bajpayee M. Genotoxicity assessment. Methods and protocols. Methods in Molecular Biology. 2nd ed. Humana Press; 2019. 376 р.
  22. ICH E9 statistical principles for clinical trials.
  23. E9 Statistical Principles for Clinical Trials. U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) Center for Biologics Evaluation and Research (CBER); 1998. Available from:
  24. Shan G, Banks S, Miller JB, et al. Statistical advances in clinical trials and clinical research. Alzheimers Dement (N Y). 2018;4:366-371.
  25. Mamur S, Yuzbasioglu D, Altok K, et al. Determination of genotoxic effects in hemodialysis patients with chronic kidney disease and the role of diabetes mellitus and other biochemical parameters. Mutat Res. 2019;844:46-53.
  26. Palazzo RP, Bagatini PB, Schefer PB, et al. Genomic instability in patients with type 2 diabetes mellitus on hemodialysis. Rev Bras Hematol Hemoter. 2012;34(1):31-35.
  27. Schupp N, Rutkowski P, Sebeková K, et al. AT1 receptor antagonist candesartan attenuates genomic damage in peripheral blood lymphocytes of patients on maintenance hemodialysis treatment. Kidney Blood Press Res. 2011;34(3): 167-172.
  28. Sandoval SB, Stoyanova E, Coll E, et al. Genetic damage in chronic renal failure patients is associated with the glomerular filtration rate index. Mutagenesis. 2010;25(6):603-608.
  29. Roth JM, Restani RG, Gonçalves TT, et al. Genotoxicity evaluation in chronic renal patients undergoing hemodialysis and peritoneal dialysis, using the micronucleus test. Genet Mol Res. 2008;7(2):433-443.
  30. Fragedaki E, Nebel M, Schupp N, et al. Genomic damage and circulating AGE levels in patients undergoing daily versus standard haemodialysis. Nephrol Dial Transplant. 2005;20(9):1936-1943.
  31. Stopper H, Meysen T, Böckenförde A, et al. Increased genomic damage in lymphocytes of patients before and after long-term maintenance hemodialysis therapy. Am J Kidney Dis. 1999;34(3):433-437.
  32. Sirota NP, Zhanataev AK, Kuznetsova EA, et al. Some causes of inter-labolatory variation in the results of comet assay. Mutation Res. 2014;770:16-22.
  33. Mamur S, Unal F, Altok K, et al. DNA damage in hemodialysis patients with chronic kidney disease; a test of the role of diabetes mellitus; a comet assay investigation. Mutat Res Genet Toxicol Environ Mutagen. 2016;800-801:22-27.
  34. Ersson C, Odar-Cederlöf I, Fehrman-Ekholm I, Möller L. The effects of hemodialysis treatment on the level of DNA strand breaks and oxidative DNA lesions measured by the comet assay. Hemodial Int. 2013;17(3):366-373.
  35. Stoyanova E, Pastor S, Coll E, et al. Base excision repair capacity in chronic renal failure patients undergoing hemodialysis treatment. Cell Biochem Funct. 2014;32(2):177-182.
  36. Bagatini PB, Palazzo RP, Rodrigues MT, et al. Induction and removal of DNA damage in blood leukocytes of patients with type 2 diabetes mellitus undergoing hemodialysis. Mutat Res. 2008;657(2):111-115.
  37. Horoz M, Bolukbas C, Bolukbas FF, et al. Assessment of peripheral DNA damage by alkaline comet assay in maintenance hemodialysis subjects with hepatitis C infection. Mutat Res. 2006;596(1-2):137-142.
  38. Domenici FA, Vannucchi MT, Jordão AA Jr, Meirelles MS, Vannucchi H. DNA oxidative damage in patients with dialysis treatment. Ren Fail. 2005;27(6):689-694.
  39. Kan E, Undeğer U, Bali M, Başaran N. Assessment of DNA strand breakage by the alkaline COMET assay in dialysis patients and the role of Vitamin E supplementation. Mutat Res. 2002;520(1-2):151-159.
  40. Stopper H, Boullay F, Heidland A, et al. Comet-assay analysis identifies genomic damage in lymphocytes of uremic patients. Am J Kidney Dis. 2001;38(2):296-301.
  41. Cengiz K, Block AM, Hossfeld DK, et al. Sister chromatid exchange and chromosome abnormalities in uremic patients. Cancer Genet Cytogenet. 1988;36(1):55-67. 10.1016/0165-4608(88)90075-1.
  42. Aykanat B, Demircigil GC, Buyan N, et al. Micronuclei and other nuclear anomalies in buccal epithelial cells of children with chronic kidney disease. Arh Hig Rada Toksikol. 2016;67(4):317-325.
  43. Aykanat B, Demircigil GC, Fidan K, et al. Basal damage and oxidative DNA damage in children with chronic kidney disease measured by use of the comet assay. Mutat Res. 2011;725 (1-2):22-28.
  44. Cakmak Demircigil G, Aykanat B, Fidan K, et al. Micronucleus frequencies in peripheral blood lymphocytes of children with chronic kidney disease. Mutagenesis. 2011;26(5):643-650.
  45. Gandhi G, Tung G. Sensitivity and specificity prediction of the buccal micronucleus cytome assay in end-stage renal disease patients on dialysis: A case-control study. Mutat Res. 2017;822:1-9.
  46. Ersson C, Thorman R, Rodhe Y, et al. DNA damage in salivary gland tissue in patients with chronic kidney disease, measured by the comet assay. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2011;112(2):209-215.
  47. Horoz M, Bolukbas FF, Bolukbas C, et al. The association of circulating leptin level with peripheral DNA damage in hemodialysis subjects. Clin Biochem. 2006;39(9):918-922.
  48. Stopper H, Hempel K, Reiners C, et al. Pilot study for comparison of reticulocyte-micronulei with lymphocyte-micronuclei in human biomonitoring. Toxicol Lett. 2005;156(3):351-360.
  49. Buemi M, Costa C, Floccari F, et al. Genomic damage in endothelial progenitor cells from uremic patients in hemodialysis. J Nephrol. 2010;23(3):328-334.
  50. Pruett B, Johnson S, O’Keefe N. Improving IV iron and anemia management in the hemodialysis setting: a collaborative CQI approach. Nephrol Nurs J. 2007;34(2):206-213.
  51. Vaziri ND. Toxic effects of IV iron preparations in CKD patients. Nephrol News Issues. 2014;28(2):4-5.
  52. Дурнев А.Д., Жанатаев А.К., Шредер О.В., Середенина В.С. Генотоксические поражения и болезни // Молекулярная медицина. – 2013. – № 3. – С. 3–19. [Durnev AD, Zhanatayev AK, Schroeder OV, Seredenina VS. Genotoxic events and diseases. Molecular medicine. 2013;(3):3-19. (In Russ.)]
  53. Kobras K, Schupp N, Nehrlich K, et al. Relation between different treatment modalities and genomic damage of end-stage renal failure patients. Kidney Blood Press Res. 2006;29(1):10-17.
  54. Corredor Z, Rodríguez-Ribera L, Silva I, et al. Levels of DNA damage in peripheral blood lymphocytes of patients undergoing standard hemodialysis vs on-line hemodiafiltration: A comet assay investigation. Mutat Res Genet Toxicol Environ Mutagen. 2016;808:1-7. 008.
  55. Rodríguez-Ribera L, Pastor S, Corredor Z, et al. Genetic damage in patients moving from hemodialysis to online hemodiafiltration. Mutagenesis. 2016;31(2):131-135.
  56. Schupp N, Stopper H, Rutkowski P, et al. Effect of different hemodialysis regimens on genomic damage in end-stage renal failure. Semin Nephrol. 2006;26(1):28-32.
  57. Müller C, Eisenbrand G, Gradinger M, et al. Effects of hemodialysis, dialyser type and iron infusion on oxidative stress in uremic patients. Free Radic Res. 2004;38(10):1093-1100.
  58. Stopper H, Treutlein AT, Bahner U, et al. Reduction of the genomic damage level in haemodialysis patients by folic acid and vitamin B12 supplementation. Nephrol Dial Transplant. 2008;23(10):3272-3279.
  59. Schardong J, Brito VB, Dipp T, et al. Intradialytic neuromuscular electrical stimulation reduces DNA damage in chronic kidney failure patients: a randomized controlled trial. Biomarkers. 2018;23(5):495-501.
  60. Rodríguez-Ribera L, Corredor Z, Silva I, et al. Vitamin E-coated dialysis membranes reduce the levels of oxidative genetic damage in hemodialysis patients. Mutat Res. 2017;815:16-21.
  61. Spormann TM, Albert FW, Rath T, et al. Anthocyanin/polyphenolic-rich fruit juice reduces oxidative cell damage in an intervention study with patients on hemodialysis. Cancer Epidemiol Biomarkers Prev. 2008;17(12): 3372-3380.
  62. Corredor Z, Rodríguez-Ribera L, Coll E, et al. Unfermented grape juice reduce genomic damage on patients undergoing hemodialysis. Food Chem Toxicol. 2016;92:1-7.
  63. Bonassi S, Znaor A, Ceppi M, et al. An increased micronucleus frequency in peripheral blood lymphocytes predicts the risk of cancer in humans. Carcinogenesis. 2007;28(3):625-631.
  64. Corredor Z, Stoyanova E, Rodríguez-Ribera L, et al. Genomic damage as a biomarker of chronic kidney disease status. Environ Mol Mutagen. 2015;56(3):301-312. 21911.
  65. Stopper H, Schupp N, Bahner U, et al. Genomic damage in end-stage renal failure: potential involvement of advanced glycation end products and carbonyl stress. Semin Nephrol. 2004;24(5):474-478.
  66. Coll E, Stoyanova E, Rodríguez-Ribera L, et al. Genomic damage as an independent predictor marker of mortality in hemodialysis patients. Clin Nephrol. 2013;80(2):81-87.
  67. Lee YC, Hung SY, Wang HK, et al. Is there different risk of cancer among end-stage renal disease patients undergoing hemodialysis and peritoneal dialysis? Cancer Med. 2018;7(2):485-498.
  68. Heidland A, Bahner U, Vamvakas S. Incidence and spectrum of dialysis-associated cancer in three continents. Am J Kidney Dis. 2000;35(2):347-353.
  69. Wu CF, Pang ST, Shee JJ, et al. Identification of genetic alterations in upper urinary tract urothelial carcinoma in end-stage renal disease patients. Genes Chromosomes Cancer. 2010;49(10): 928-934.
  70. Liu SL, Qi L, Han WQ, et al. Shorter hemodialysis duration is a risk factor for the recurrence of urothelial carcinoma of the bladder in patients on maintenance hemodialysis. Clin Transl Oncol. 2016;18(3):304-309.
  71. Стецюк Е.А., Третьяков Б.В., Калашников С.В., Петров С.Н. Прощание с классическим гемодиализом и гемодиализ XXI века // Нефрология. – 2003. – Т. 7. – № 2. – С. 25–30. [Stetsyuk EA, Tretyakov BV, Kalashnikov SV, Petrov SN. Farewell to classical hemodialysis and the hemodialysis of the XXI century. Nephrology. 2003;7(2):25-30. (In Russ.)]
  72. Дурнев А.Д. Антимутагенез и антимутагены // Физиология человека. – 2018. – Т. 44. – № 3. – С. 116–137. [Durnev AD. Antimutagenesis and antimutagens. Human Physiology. 2018;44(3):116-137. (In Russ.)].
  73. Дурнев А.Д., Середенин С.Б. Мутагены (Скрининг и фармакологическая профилактика воздействий). – М.: Медицина, 1998. – 326 с. [Durnev AD, Seredenin SB. Mutageny (Skrining i farmakologicheskaya profilaktika vozdeystviy). Moscow: Meditsina; 1998. 326 р. (In Russ.)]
  74. Мавлонхужаев А.Н., Умарова З.Ф. Качество жизни у больных с хронической почечной недостаточностью в 5 стадии, получающих программный гемодиализ и возможные пути ее коррекции // Авиценна. – 2019. – № 38. – С. 18–20. [Mavlonkhuzhayev AN, Umarova ZF. Quality of life in patients with chronic kidney disease in the 5 stage receiving program hemodialysis and possible ways of its correction. Avicenna. 2019;(38):18-20. (In Russ.)]
  75. Pastor S, Coll E, Rodríguez-Ribera L, et al. Influence of Carnicor, Venofer, and Sevelamer on the levels of genotoxic damage in end-stage renal disease patients. Environ Mol Mutagen. 2018;59(4):302-311.
  76. Жанатаев А.К., Дурнев А.Д., Середенин С.Б. Сравнительное изучение антимутагенной активности афобазола при различных режимах применения // Бюллетень экспериментальной биологии и медицины. – 2000. – Т. 130. – № 11. – С. 539–542. [Zhanataev AK, Durnev AD, Seredenin SB. Antimutagenic activity of afobazole in various regimens of treatment. Bulletin of Experimental Biology and Medicine. 2000;130(11): 539-542. (In Russ.)]
  77. Rangel-López A, Paniagua-Medina ME, Urbán-Reyes M, et al. Genetic damage in patients with chronic kidney disease, peritoneal dialysis and haemodialysis: a comparative study. Mutagenesis. 2013;28(2):219-225. 1093/mutage/ges075.

Supplementary files

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Figure: 1. Frequency of micronuclei in lymphocytes of patients on hemodialysis therapy and control groups, mean ± SEM (n = 7, p <0.05)

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Figure: 2. Correlation of the frequency of micronuclei (MN) in binucleated lymphocytes in patients undergoing hemodialysis and control groups. Each point on the graph represents the mean for one study (n = 7)

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