Genetic damage in chronic renal failure patients is associated with the glomerular filtration rate index

Sandoval, Silvia Berenice; Stoyanova, Elitsa; Coll, Elisabet; Pastor, Susana; Reyes, Joselyn; Enrique, Andrés; Ballarín, J.; Xamena, N.; Marcos, Ricard

doi:10.1093/mutage/geq047

Cited by 26 publications

(16 citation statements)

References 35 publications

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“…This agrees with Stopper et al (5), who found that in comparison with healthy controls, MN in PBL is increased approximately 2-fold in pre-dialysis CKD patients. Our study concurs with results in previous studies showing increased cytogenetic effects with regards to MN frequencies in pre-dialysis CKD and in patients with a different modality of dialysis treatment (5,14,39–41). …”

Section: Discussionsupporting

confidence: 93%

Genetic damage in patients with chronic kidney disease, peritoneal dialysis and haemodialysis: a comparative study

et al. 2013

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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.

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Section: Discussionsupporting

confidence: 93%

Genetic damage in patients with chronic kidney disease, peritoneal dialysis and haemodialysis: a comparative study

et al. 2013

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“…In patients with ESRD, genomic damage has been shown by numerous biomarkers, such as the analysis of sister chromatid exchange and chromosomal aberrations (Cengiz et al, 1988, Lialiaris et al, 2010, MN frequency (Stopper et al, 1999;Sandoval et al, 2010), comet assay in peripheral lymphocytes (Stopper et al, 2001;Kobras et al, 2006;Aykanat et al, 2011), 8-hydroxy 2-deoxyguanosine content in leukocytes (Tarng et al, 2004), and mitochondrial DNA deletions in skeletal muscle tissue and hair follicles (Liu et al, 2001). Our results also confirmed that patients with ESRD exhibit increased levels of genomic damage, as measured by the MN assay.…”

Section: Discussionsupporting

confidence: 82%

“…In the literature, there are a few previous studies using the MN assay in peripheral blood lymphocytes of patients with chronic renal failure (Stopper et al, 1999;Kobras et al, 2006;Schupp et al, 2008;Sandoval et al, 2010). All of them show increased MN levels in patients with chronic renal failure.…”

Section: Discussionmentioning

confidence: 99%

Relationship Between Genomic Damage and Clinical Features in Dialysis Patients

Güven

Altıparmak

Trabulus

et al. 2013

Genetic Testing and Molecular Biomarkers

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Patients with end-stage renal disease display enhanced genomic damage. We investigated the presence of genomic damage in the peripheral lymphocytes by using the micronucleus (MN) test and the factors associated with the MN frequency in hemodialysis (HD) and peritoneal dialysis (PD) patients. We studied 121 dialysis patients (60 HD and 61 PD) and 129 age- and gender-matched healthy controls. The MN analysis, used as a biomarker of chromosomal/DNA damage, was performed in peripheral lymphocytes by the cytokinesis-block method. Univariate analysis showed a significantly higher MN frequency in all patients in comparison with the controls (7.6% ± 0.3% vs. 4.9% ± 0.2%, respectively, p<0.001). Significantly higher frequency of MN was observed in both HD and PD patients compared to controls (7.7% ± 0.5% vs. 4.9% ± 0.2%, p<0.001 and 7.5% ± 0.5% vs. 4.9% ± 0.2%, p<0.001, respectively). Multivariate analysis was performed, and it showed that the low-density lipoprotein level was the only independent determinant of increasing MN frequency in our patients (β=0.16, t=2.172, p<0.05). There is no significant difference in terms of genomic damage between two dialysis modalities, which suggests that PD may not be a more reliable choice in terms of genomic damage.

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“…The biomarkers used in these studies were micronuclei in peripheral blood lymphocytes (PBL) (7,(25)(26)(27) and BEC (9), chromosome aberrations and sister chromatid exchanges (28,29), and DNA strand breaks (comet assay) (26-28, 30, 31). The only reports regarding children with CKD were our recent studies using the MN and comet assays in PBL of children (15,16).…”

Section: Resultsmentioning

confidence: 99%

Micronuclei and other nuclear anomalies in buccal epithelial cells of children with chronic kidney disease

Aykanat

Demircigil

Buyan

et al. 2016

Archives of Industrial Hygiene and Toxicology

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The objective of this study was to reveal the likely genomic instability in children with chronic kidney disease (CKD) using micronucleus (MN) assay on buccal epithelial cells (BEC). We investigated the frequencies of micronuclei and other nuclear anomalies, such as nuclear buds, binucleated cells, condensed chromatin, and karyorrhectic and pyknotic cells in BEC. Children with CKD were grouped as follows: children in the pre-dialysis (PreD) stage (N=17), children on regular haemodialysis (HD) (N=14), and children who have undergone transplantation (Tx) (N=17). As a control group, twenty age-and gender-matched healthy children were selected. The MN frequency in BEC of all groups of children with CKD was significantly elevated (5-to 7-fold) as compared to the control group (p<0.001). In contrast, the frequencies of nuclear buds were not significantly higher in the study groups compared to the control group. The frequencies of binucleated cells and condensed chromatin cells were significantly higher in all subgroups of children with CKD relative to the control group (p<0.001). Our results show that the BEC of pediatric PreD, HD, and Tx patients with CKD display increased cytogenetic, cytokinetic, and cytotoxic effects. They also point to the sensitivity and usefulness of the BEC MN assay in the assessment of genetic susceptibility of patients with CKD.

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Genetic damage in chronic renal failure patients is associated with the glomerular filtration rate index

Cited by 26 publications

References 35 publications

Genetic damage in patients with chronic kidney disease, peritoneal dialysis and haemodialysis: a comparative study

Genetic damage in patients with chronic kidney disease, peritoneal dialysis and haemodialysis: a comparative study

Relationship Between Genomic Damage and Clinical Features in Dialysis Patients

Micronuclei and other nuclear anomalies in buccal epithelial cells of children with chronic kidney disease

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