Oxidative DNA Damage Is Elevated in Renal Patients Undergoing Haemodialysis

Twyla Moffitt, Peter J Garrett, Mary PA Hannon-Fletcher

Research output: Contribution to journalArticlepeer-review


Background: End stage renal disease (ESRD) is associated with an increase in oxidative stress, cardiovascular disease and cancer. The main treatment for ESRD is haemodialysis (HD), which induces repetitive bouts of oxidative stress through membrane biocompatibility and endotoxin challenge. The resulting higher levels of reactive oxygen species in turn produce increased levelsof oxidative DNA damage leading to genomic instability which may influence the higher risk of cancer reported in HD patients. Our aims were to measure levels of oxidative DNA damage in HD patients and in age and gender matched control volunteers. Methods: Thirty eight patients receiving HD in the Western Health and Social Services Trust (WHSCT) and 8 healthy volunteers were recruited. Volunteers gave informed consent and non-fasting morning blood samples were taken and assessed for DNA disruption using the comet assay modified to identify oxidative specific damage. Results: The HD patients had significantly elevated levels of alkaline DNA damage (19.46%± 1.37% vs 3.86% ± 1.36% tail DNA, p <0.05) and oxidative DNA damage formamidepyrimidine DNA glycosilase (5.81% ± 1.08% vs 1.23% ± 0.43% tail DNA, p <0.01) and endonuclease III (6.04%± 1.00% vs 1.98% ± 0.70% tail DNA, p <0.01) compared to controls, respectively. A positive correlation was observed between the duration on dialysis (months) and levels of Endo III specific damage (p = 0.041). Conclusion: The significant increase in oxidative DNA damage and the positive correlation with duration of HD treatment and Endo III damage may contribute to the increased cancer risk observed in this patient group. Studies are required to investigate the best way to reduce this damage.
Original languageEnglish
Pages (from-to)421-428
JournalOpen Journal of Preventive Medicine
Issue number6
Publication statusPublished - 11 Jun 2014

Bibliographical note

Reference text: Balsam, A., El Kossi, M., Lord, R. and El Nahas, A. (2009) Cardiovascular Disease on Hemodialysis: Predictors of
Atherosclerosis and Survival. Hemodialysis International, 13, 278-285.
[2] Menon, V. and Sarnak, M. (2005) The Epidemiology of Chronic Kidney Disease Stages 1 to 4 and Cardiovascular Disease:
A High-Risk Combination. American Journal of Kidney Disease, 45, 223-232.
[3] Feest, T. (2007) Epidemiology and Causes of Chronic Renal Failure. Medicine, 35, 438-441.
[4] Stoyanova, E., Sandoval, S., Zuniga, L., El-Yamani, N., Coll, E., Pastor, S., Reyes, J., Andrés, E., Ballarin, J., Xamena,
N. and Marcos, R. (2009) Oxidative DNA Damage in Chronic Renal Failure Patients. Nephrology Dialysis Transplantation,
25, 879-885. http://dx.doi.org/10.1093/ndt/gfp575
[5] Maisonneuve, P., Agodoa, L., Gellert, R.J.H., Stewart, G., Buccianti, A.B., Lowenfels, R.A., Wolfe, E., Jones, A.P.,
Disney, D., Briggs, M., McCredie, P. and Boyle, P. (1999) Cancer in Patients on Dialysis for End-Stage Renal Disease:
T. Moffitt et al.
An International Collaborative Study. Lancet, 354, 93-99. http://dx.doi.org/10.1016/S0140-6736(99)06154-1
[6] Locatelli, F., Canaud, B., Eckardt, K.U., Stenvinkel, P., Wanner, C. and Zoccali, C. (2003) Oxidative Stress in End-
Stage Renal Disease: An Emerging Threat to Patient Outcome. Nephrology Dialysis Transplantation, 18, 1272-1280.
[7] Müller, C., Eisenbrand, G., Gradinger, M., Rath, T., Albert, F.W., Vienken, J., Singh, R., Farmer, P.B., Stockis, J.P.
and Janzowski, C. (2004) Effects of Hemodialysis, Dialyser Type and Iron Infusion on Oxidative Stress in Uremic Patients.
Free Radical Research, 38, 1093-1100. http://dx.doi.org/10.1080/10715760400011452
[8] Valentini, J., Grotto, D., Paniz, C., Roehrs, M., Burg, G. and Garcia, S. (2008) The Influence of the Heamodialysis
Treatment Time under Oxidative Stress Biomarkers in Chronic Renal Failure Patients. Biomedicine and Pharmacotherapy,
62, 378-382. http://dx.doi.org/10.1016/j.biopha.2007.10.017
[9] Bossola, M., Muscaritoli, M., Tazza, L., Giungi, S., Tortorelli, A., Rossi Fanelli, F. and Luciani, G. (2005) Malnutrition
in Hemodialysis Patients: What Therapy? American Journal of Kidney Diseases, 46, 371-386.
[10] Tarng, D., Huang, T., Wei, Y., Liu, T., Chen, H., Chen, T. and Yang, W. (2000) 8-Hydroxy-2’-Deoxyguanosine of
Leukocyte DNA as a Marker of Oxidative Stress in Chronic Hemodialysis Patients. American Journal of Kidney Diseases,
36, 934-944. http://dx.doi.org/10.1053/ajkd.2000.19086
[11] Inamoto, H., Ozaki, R., Matsuzaki, T., Wakui, M., Saruta, T. and Osawa, A. (1991) Incidence and Mortality Pattern of
Malignancy and Factors Affecting the Risk of Malignancy in Dialysis Patients. Nephron, 59, 611-617.
[12] Ragheb, N., Port, F. and Schwartz, G. (1991) The Risk of Cancer for Patients on Dialysis: A Review. Seminat in Dialysis,
4, 253-257. http://dx.doi.org/10.1111/j.1525-139X.1991.tb00104.x
[13] Ishikawa, I., Saito, Y., Shikura, N., Kitada, H., Shinoda, A. and Suzuki, S. (1990) Ten-Year Prospective Study on the
Development of Renal Cell Carcinoma in Dialysis Patients. American Journal of Kidney Diseases, 16, 453-458.
[14] Gedik, C. and Collins, A. (2005) ESCODD (European Standards Committee on Oxidative DNA Damage). Establishing
the Background Level of Base Oxidation in Human Lymphocyte DNA: Results of an Interlaboratory Validation Study.
FASEB Journal, 19, 82-84.
[15] Singh, N., McCoy, M., Tice, R. and Schneider, E. (1988) A Simple Technique for Quantitation of Low Levels of DNA
Damage in Individual Cells. Experimental Cell Research, 175, 184-191.
[16] Collins, A.R., Duthie, S.J. and Dobson, V.L. (1993) Direct Enzymic Detection of Endogenous Oxidative Base Damage
in Human Lymphocyte DNA. Carcinogenesis, 14, 1733-1735. http://dx.doi.org/10.1093/carcin/14.9.1733
[17] Hininger, I., Chollat-Namy, A., Sauvaigo, S., Osman, M., Faure, H., Cadet, J., Favier, A. and Roussel, A.M. (2004)
Assessment of DNA Damage by Comet Assay on Frozen Total Blood: Method and Evaluation in Smokers and Non-
Smokers. Mutation Research, 14, 75-80.
[18] Dusïnská, M. and Collins, A. (1996) Detection of Oxidised Purines and UV Induced Photoproducts in DNA of Single
Cells, by Inclusion of Lesionspecific Enzymes in the Comet Assay. Alternatives Laboratory Animals, 24, 405-411.
[19] Stopper, H., Boullay, F., Heidland, A. and Bahner, U. (2001) Comet-Assay Analysis Identifies Genomic Damage in
Lymphocytes of Uremic Patients. American Journal of Kidney Disease, 38, 296-301.
[20] Stopper, H., Meysen, T., Böckenförde, A., Bahner, U., Heidland, A. and Vamvakas, S. (1999) Increased Genomic Damage
in Lymphocytes of Patients before and after Long-Term Maintenance Hemodialysis Therapy. American Journal
of Kidney Disease, 34, 433-437. http://dx.doi.org/10.1016/S0272-6386(99)70069-7
[21] Zevin, D., Malachi, T., Gafter, U., Friedman, J. and Levi, J. (1991) Impaired DNA Repair in Patients with End-Stage
Renal Disease and Its Improvement with Hemodialysis. Mineral and Electrolyte Metabolism, 17, 303-306.
[22] Kobras, K., Schupp, N., Nehrlich, K., Adelhardt, M., Bahner, U., Vienken, J., Heidland, A., Sebekova, K. and Stopper,
H. (2006) Relation between Different Treatment Modalities and Genomic Damage of End-Stage Renal Failure Patients,
Kidney. Blood Pressure Research, 29, 10-17. http://dx.doi.org/10.1159/000092482
[23] Schupp, N., Stopper, H., Rutkowski, P., Kobras, K., Nebel, M., Bahner, U., Vienken, J. and Heidland, A. (2006) Effect
of Different Hemodialysis Regimens on Genomic Damage in End-Stage Renal Failure. Seminars in Nephrology, 26,
28-32. http://dx.doi.org/10.1016/j.semnephrol.2005.06.007
[24] Boxall, M.C., Goodship, T.H., Brown, A.L., Ward, M.C. and von Zglinicki, T. (2006) Telomere Shortening and Hemodialysis.
Blood Purification, 24, 185-189. http://dx.doi.org/10.1159/000090517
[25] Rangel-López, A., Paniagua-Medina, M.E., Urbán-Reyes, M., Cortes-Arredondo, M., Alvarez-Aguilar, C., López-Meza,
J., Ochoa-Zarzosa, A., Lindholm, B., García-López, E. and Paniagua, J.R. (2013) Genetic Damage in Patients with
T. Moffitt et al.
Chronic Kidney Disease, Peritoneal Dialysis and Haemodialysis: A Comparative Study. Mutagenesis, 8, 219-225.
[26] Yamamoto, K., Kobayashi, K., Endo, K., Miyasaka, T., Mochizuki, S., Kohori, F. and Sakai, K. (2005) Hollow-Fiber
Blood-Dialysis Membranes: Superoxide Generation, Permeation, and Dismutation Measured. International Journal of
Artificial Organs, 8, 257-262. http://dx.doi.org/10.1007/s10047-005-0315-y
[27] Tarng, D.C., Huang, T.P., Liu, T.Y., Chen, H.W., Sung, Y.J. and Wei, Y.H. (2000) Effect of Vitamin E-Bonded Membrane
on the 8-Hydroxy 2’-Deoxyguanosine Level in Leukocyte DNA of Hemodialysis Patients. Kidney International,
58, 790-799. http://dx.doi.org/10.1046/j.1523-1755.2000.00228.x
[28] Giardini, O., Taccone-Gallucci, M., Lubrano, R., Ricciardi-Tenore, G., Bandino, D., Silvi, I., Paradisi, C., Mannarino,
O., Citti, G., Elli, M., et al. (1984) Effects of Alpha-Tocopherol Administration on Red Blood Cell Membrane Lipid
Peroxidation in Hemodialysis Patients. Clinical Nephrology, 21, 174-177.


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