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      Using the cytokinesis-block micronucleus cytome assay to evaluate chromosomal DNA damage in chronic renal patients undergoing bicarbonate haemodialysis and haemodiafiltration


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          Chronic Renal Failure (CRF) patients are considered to show genomic instability and are associated with a high risk of both cardiovascular diseases and cancer. We explored DNA damage due to two dialysis treatments in 20 patients undergoing bicarbonate haemodialysis (BD), 20 undergoing haemodiafiltration (HDF) and 40 healthy subjects.


          The cytokinesis-block micronucleus (MN) assay was performed on peripheral blood lymphocytes to evaluate genetic damage.


          A higher frequency of MN in the dialysis groups compared with controls was found. The results do not show a relationship between genetic instability and the type, frequency and duration of haemodialysis. The average BD and HDF treatment time was respectively 3.8 ± 6.3 and 3.7 ± 3.9 yrs. CAT and scintigraphy was independently correlated with high levels of MN.


          Overall, the frequency of MN in CRF patients undergoing dialysis therapy was observed to be higher. Further studies need to be performed on a larger number of patients and for a longer period.

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          Most cited references35

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          Oxidative stress in uremia: nature, mechanisms, and potential consequences.

          Oxidative stress has emerged as a constant feature of chronic renal failure (CRF). The presence of oxidative stress in CRF is evidenced by an overabundance of lipid, carbohydrate, and protein oxidation products in the plasma and tissues of uremic patients and animals. We recently have shown that oxidative stress in CRF animals is associated with and, in part, owing to up-regulation of superoxide-producing enzyme, nicotinamide-adenine dinucleotide phosphate (NAD(P)H) oxidase, and down-regulation of superoxide dismutase (SOD). The functional significance of these findings was confirmed by favorable response to administration of the cell-permeable SOD-mimetic agent, tempol, in CRF rats. Oxidative stress in CRF plays an important role in the pathogenesis of the associated hypertension (oxidation of NO and arachidonic acid and vascular remodeling), cardiovascular disease (oxidation of lipoproteins, atherogenesis), neurologic disorders (nitration of brain proteins, oxidation of myelin), anemia (reduction of erythrocyte lifespan), inflammation (nuclear factor kappa B activation), fibrosis, apoptosis, and accelerated aging. The CRF-induced oxidative stress is aggravated by diabetes, uncontrolled hypertension, and autoimmune diseases, which independently increase production of reactive oxygen intermediates, and frequently are associated with CRF. In addition, dialysis treatment (blood interaction with dialyzer membrane and dialysate impurities), acute and chronic infections (blood access infection, hepatitis, and so forth), and excessive parenteral iron administration intensify CRF-associated oxidative stress and its adverse consequences in patients with end-stage renal disease. The problem is compounded by limited intake of fresh fruits and vegetables (K(+) restriction), which contain numerous natural phytochemicals and antioxidant vitamins.
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            Cardiovascular complications in chronic kidney disease.

            The risk for cardiovascular disease (CVD) morbidity and mortality remains alarmingly high in all stages of chronic kidney disease (CKD). CVD often begins before end-stage renal disease (ESRD), and patients with reduced kidney function are more likely to die of CVD than to develop ESRD. Three pathological forms of CVD should be considered in patients with CKD: alterations in cardiac geometry, including left ventricular hypertrophy, atherosclerosis, and arteriosclerosis. All are highly prevalent in patients with CKD. Although patients with CKD share many of the same risk factors for CVD as the general population, there are a number of uremia-related risk factors, such as anemia and alterations in calcium/phosphorus metabolism, that also play a role in promoting CVD. Treatment of both traditional and uremia-related risk factors should be initiated in the earlier stages of CKD. Additional clinical trials with a goal to reduce CVD are urgently needed in CKD.
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              Chronic kidney disease and risk of major cardiovascular disease and non-vascular mortality: prospective population based cohort study

              Objective To quantify associations of chronic kidney disease stages with major cardiovascular disease and non-vascular mortality in the general adult population. Design Prospective population based cohort study. Setting Reykjavik, Iceland. Participants 16 958 people aged 33-81 years without manifest vascular disease and with available information on stage of chronic kidney disease (defined by both estimated glomerular filtration rate and urinary protein) at study entry. Main outcome measures Hazard ratios for time to major coronary heart disease outcomes and mortality. Results 1210 (7%) of participants had chronic kidney disease at entry. During a median follow-up of 24 years, 4010 coronary heart disease outcomes, 559 deaths from stroke, and 3875 deaths from non-vascular causes were recorded. Compared with the reference group (estimated glomerular filtration rate 75-89 ml/min/1.73 m2 and no proteinuria), people with lower renal function within the normal range of glomerular filtration rate did not have significantly higher risk of coronary heart disease. By contrast, in 1210 (7%) participants with chronic kidney disease at entry, hazard ratios for coronary heart disease, adjusted for several conventional cardiovascular risk factors, were 1.55 (95% confidence interval 1.02 to 2.35) for stage 1, 1.72 (1.30 to 2.24) for stage 2, 1.39 (1.22 to 1.58) for stage 3a, 1.90 (1.22 to 2.96) for stage 3b, and 4.29 (1.78 to 10.32) for stage 4. Information on chronic kidney disease increased discrimination and reclassification indices for coronary heart disease when added to conventional risk factors (P<0.01). The incremental gain provided by chronic kidney disease was lower than that provided by diabetes or smoking (C index increases of 0.0015, 0.0024, and 0.0124 respectively). Hazard ratios with chronic kidney disease were 0.97 (0.82 to 1.15) for cancer mortality and 1.26 (1.07 to 1.50) for other non-vascular mortality. Conclusions In people without manifest vascular disease, even the earliest stages of chronic kidney disease are associated with excess risk of subsequent coronary heart disease. Assessment of chronic kidney disease in addition to conventional risk factors modestly improves prediction of risk for coronary heart disease in this population. Further studies are needed to investigate associations between chronic kidney disease and non-vascular mortality from causes other than cancer.

                Author and article information

                J Prev Med Hyg
                J Prev Med Hyg
                Journal of Preventive Medicine and Hygiene
                Pacini Editore SRL
                September 2016
                : 57
                : 3
                : E178-E184
                [1 ] Laboratory of Hygiene, Department of Biological and Environmental Sciences and Technologies, University of Salento, Lecce, Italy;
                [2 ] Institute of Clinical Physiology, National Research Council, Lecce, Italy;
                [3 ] Nephrology & Dialysis Special Unit, "I. Veris Delli Ponti" Hospital, Scorrano, Lecce Local Health Unit, Italy;
                [4 ] Dialysis Special Unit, "F. Pispico" Hospital, Poggiardo, Lecce Local Health Unit, Italy
                Author notes
                Correspondence: Antonella De Donno, Laboratory of Hygiene, Department of Biological and Environmental Sciences and Technologies, University of Salento, via Prov. Lecce-Monteroni, 73100 Lecce, Italy - Tel. +39 0832 298687 - Fax +39 0832 298626 - Email: antonella.dedonno@ 123456unisalento.it

                Authors' Contributions

                MG, AZ, GS and ADD conceived, designed and coordinated the research. MD'A, AI, FS and TG collected data and samples. MG, AZ, MRT and MD'A performed the data quality control. MG and FB optimized the informatics database. MG performed the statistical analyses. MG, AZ, MRT, GS, MD'A and DDA evaluated the results. MG, AZ and MRT wrote the manuscript. All Authors revised the manuscript and gave their contribution to improve the paper. All authors read and approved the final manuscript.

                © Copyright by Pacini Editore SRL, Pisa, Italy

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License, which permits for noncommercial use, distribution, and reproduction in any digital medium, provided the original work is properly cited and is not altered in any way. For details, please refer to http://creativecommons.org/licenses/by-nc-nd/3.0/

                : 08 December 2015
                : 14 June 2016
                Original Article

                chronic renal failure (crf),dna damage,micronucleus (mn)


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