Oxidative DNA Damage Is Elevated in Renal Patients Undergoing Haemodialysis

Abstract

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 itself induces repetitive bouts of oxidative stress through membrane biocompatibility and endotoxin challenge. The resulting higher levels of reactive oxygen species in turn produce increased levels of 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.

Amino acids exchange obtained from CKD patients via Exome Sequencing differ radically from those of natural variants 1000 genome and genomAD databases

“…It is a congruence of many vascular diseases with patients having dysfunctions of many physiological pathways. The pathology is in ltrated by other diseases like: diabetes, hypertension [43][44][45], cardiovascular morbidity [46,47] as well as many genetic abnormalities like genomic instability [47,[48][49][50][51]and instability which is later translated into chromosomal damage and ultimately culminating to renal pathologies. Recent progress in genome-wide association studies revealed SNPs linked to different pathologies associated to CKD like: hypertension [52], coronary artery disease [53], subclinical vascular disease [54] and overlapping between genetic variants observed in CKD patients and cardiovascular pathologies [55].…”

Amino acids exchange in patients with CKD as obtained via exome sequencing differ radically from those of natural variants 1000 genome and genomAD databases

“…It is a congruence of many vascular diseases with patients having dysfunctions of many physiological pathways. The pathology is in ltrated by other diseases like: diabetes, hypertension [43][44][45], cardiovascular morbidity [46,47] as well as many genetic abnormalities like genomic instability [47,[48][49][50][51]and instability which is later translated into chromosomal damage and ultimately culminating to renal pathologies. Recent progress in genome-wide association studies revealed SNPs linked to different pathologies associated to CKD, like hypertension [52], coronary artery disease [53], subclinical vascular disease [54] and overlapping between genetic variants observed in CKD patients and cardiovascular pathologies [55].…”

Genetic Variants Associated with Chronic Kidney Disease in a Spanish Population

“…This pathology has a complicated interrelationship with other diseases 2,3 . Diabetes (DM) and hypertension (HT) are the primary risk factors for CKD 4 , and CKD is also associated with cardiovascular morbidity and mortality 5,6 , even in early stages and in young patients 7 .CKD patients are also characterized by a high genomic instability [8][9][10][11] . This instability could be translated to high levels of genetic damage measured by the incidence of chromosomal damage (micronuclei) when their cells are challenged with ionizing radiation 12 and could be either the cause or the consequence of renal pathologies.…”

“…CKD patients are also characterized by a high genomic instability [8][9][10][11] . This instability could be translated to high levels of genetic damage measured by the incidence of chromosomal damage (micronuclei) when their cells are challenged with ionizing radiation 12 and could be either the cause or the consequence of renal pathologies.…”