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Genetic damage in patients with chronic kidney disease, peritoneal dialysis and haemodialysis: a comparative study
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...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3570793/ https://www.ncbi.nlm.nih.gov/pubmed/23408844 http://dx.doi.org/10.1093/mutage/ges075 |
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author | Rangel-López, Angélica Paniagua-Medina, Maria Eugenia Urbán-Reyes, Marcia Cortes-Arredondo, Martha Álvarez-Aguilar, Cleto López-Meza, Joel Ochoa-Zarzosa, Alejandra Lindholm, Bengt García-López, Elvia Paniagua, José Ramón |
author_facet | Rangel-López, Angélica Paniagua-Medina, Maria Eugenia Urbán-Reyes, Marcia Cortes-Arredondo, Martha Álvarez-Aguilar, Cleto López-Meza, Joel Ochoa-Zarzosa, Alejandra Lindholm, Bengt García-López, Elvia Paniagua, José Ramón |
author_sort | Rangel-López, Angélica |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-3570793 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-35707932013-02-25 Genetic damage in patients with chronic kidney disease, peritoneal dialysis and haemodialysis: a comparative study Rangel-López, Angélica Paniagua-Medina, Maria Eugenia Urbán-Reyes, Marcia Cortes-Arredondo, Martha Álvarez-Aguilar, Cleto López-Meza, Joel Ochoa-Zarzosa, Alejandra Lindholm, Bengt García-López, Elvia Paniagua, José Ramón Mutagenesis Original Manuscript 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. Oxford University Press 2013-03 2013-02-25 /pmc/articles/PMC3570793/ /pubmed/23408844 http://dx.doi.org/10.1093/mutage/ges075 Text en © The Author 2013. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/3.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com. |
spellingShingle | Original Manuscript Rangel-López, Angélica Paniagua-Medina, Maria Eugenia Urbán-Reyes, Marcia Cortes-Arredondo, Martha Álvarez-Aguilar, Cleto López-Meza, Joel Ochoa-Zarzosa, Alejandra Lindholm, Bengt García-López, Elvia Paniagua, José Ramón Genetic damage in patients with chronic kidney disease, peritoneal dialysis and haemodialysis: a comparative study |
title | Genetic damage in patients with chronic kidney disease, peritoneal dialysis and haemodialysis: a comparative study |
title_full | Genetic damage in patients with chronic kidney disease, peritoneal dialysis and haemodialysis: a comparative study |
title_fullStr | Genetic damage in patients with chronic kidney disease, peritoneal dialysis and haemodialysis: a comparative study |
title_full_unstemmed | Genetic damage in patients with chronic kidney disease, peritoneal dialysis and haemodialysis: a comparative study |
title_short | Genetic damage in patients with chronic kidney disease, peritoneal dialysis and haemodialysis: a comparative study |
title_sort | genetic damage in patients with chronic kidney disease, peritoneal dialysis and haemodialysis: a comparative study |
topic | Original Manuscript |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3570793/ https://www.ncbi.nlm.nih.gov/pubmed/23408844 http://dx.doi.org/10.1093/mutage/ges075 |
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