title: Genetic damage in patients with chronic kidney disease, peritoneal dialysis and haemodialysis: a comparative study.
abstract: Patients with chronic kidney disease (CKD) have signs of genomic instability and, as a consequence, extensive genetic damage, possibly due to accumulation of uraemic toxins, oxidative stress mediators and other endogenous substances with genotoxic properties. We explored factors associated with the presence and background levels of genetic damage in CKD. A cross-sectional study was performed in 91 CKD patients including pre-dialysis (CKD patients; n = 23) and patients undergoing peritoneal dialysis (PD; n = 33) or haemodialysis (HD; n = 35) and with 61 healthy subjects, divided into two subgroups with the older group being in the age range of the patients, serving as controls. Alkaline comet assay and cytokinesis-block micronucleus assay in peripheral blood lymphocytes were used to determine DNA and chromosome damage, respectively, present in CKD. Markers of oxidative stress [malondialdehyde (MDA), advanced glycation end products (AGEs), thiols, advanced oxidation protein products and 8-hydroxy-2'-deoxyguanosine] and markers of inflammation (C-reactive protein, interleukin-6 and tumour necrosis factor alpha) were also measured. Micronucleus (MN) frequency was significantly higher (P < 0.05) in the CKD group (46±4‰) when compared with the older control (oC) group (27.7±14). A significant increase in MN frequency (P < 0.05) was also seen in PD patients (41.9±14‰) versus the oC group. There was no statistically significant difference for the HD group (29.7±15.6‰; P = NS) versus the oC group. Comet assay data showed a significant increase (P < 0.001) of tail DNA intensity in cells of patients with CKD (15.6±7%) with respect to the total control (TC) group (11±1%). PD patients (14.8±7%) also have a significant increase (P < 0.001) versus the TC group. Again, there was no statistically significant difference for the HD group (12.5±3%) compared with the TC group. Patients with MN values in the upper quartile had increased cholesterol, triglycerides, AGEs and MDA levels and lower albumin levels. Multiple logistic regression analysis showed that male gender, diabetes and treatment modality were independently associated with higher levels of DNA damage. Our results suggest that oxidative stress, diabetes, gender and dialysis modality in CKD patients increased DNA and chromosome damage. To confirm these data, prospective clinical trials need to be performed.
authors: Medical Research Unit on Nephrological Diseases, Specialties Hospital, National Medical Centre, Century XXI, Mexican Institute for Social Security (IMSS), Mexico City, Mexico. ragn62@prodigy.net.mx
authors: Angélica
authors: A
authors: Rangel-López
authors: Maria Eugenia
authors: ME
authors: Paniagua-Medina
authors: Marcia
authors: M
authors: Urbán-Reyes
authors: Martha
authors: M
authors: Cortes-Arredondo
authors: Cleto
authors: C
authors: Alvarez-Aguilar
authors: Joel
authors: J
authors: López-Meza
authors: Alejandra
authors: A
authors: Ochoa-Zarzosa
authors: Bengt
authors: B
authors: Lindholm
authors: Elvia
authors: E
authors: García-López
authors: José Ramón
authors: JR
authors: Paniagua
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis / Q000378:metabolism; D043171:Chromosomal Instability; D020552:Comet Assay; D003430:Cross-Sectional Studies; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000097:blood; D005260:Female; D017127:Glycation End Products, Advanced / Q000097:blood; D006801:Humans; D007249:Inflammation; D015850:Interleukin-6 / Q000097:blood; D016015:Logistic Models; D008214:Lymphocytes / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D015162:Micronucleus Tests; D008875:Middle Aged; D018384:Oxidative Stress; D010530:Peritoneal Dialysis / Q000009:adverse effects*; D006435:Renal Dialysis / Q000009:adverse effects*; D051436:Renal Insufficiency, Chronic / Q000235:genetics / Q000503:physiopathology*; D012709:Serum Albumin / Q000032:analysis; D014280:Triglycerides / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D015415:Biomarkers; D017127:Glycation End Products, Advanced; D015850:Interleukin-6; D012709:Serum Albumin; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; D008315:Malondialdehyde; D000080242:8-Hydroxy-2'-Deoxyguanosine; D002097:C-Reactive Protein; D003849:Deoxyguanosine