Micronucleus frequency in chronic kidney disease patients: A review.

BACKGROUND: Chronic kidney disease (CKD) is defined as a gradual loss of renal function progressing from very mild damage, with no obvious symptoms in stage one, to complete kidney failure in stage five, which ultimately requires kidney replacement therapy by organ transplantation or dialysis. Cancer incidence and other health problems, mainly diabetes and hypertension, are elevated in CKD, ultimately leading to elevated mortality. METHODS: A literature search on the induction of micronuclei (MN) as endpoint for genomic damage in white blood cells and buccal mucosa cells of CKD patients was conducted. Possible associations with disease stage, treatment modalities, and vitamin or antioxidant supplementations were analyzed. RESULTS: In total, 26 studies were enclosed in the data analysis. Patient groups in the predialysis or hemodialysis state of the disease exhibit higher levels of genomic damage, measured as micronucleus frequency in peripheral blood lymphocytes and buccal mucosa cells, than healthy control groups. Genomic damage seems to increase with the disease stage during the predialysis phase. The association with dialysis regimens or with years on dialysis is less clear, but there are indications that efficient removal of uremic toxins is beneficial. Patients with CKD receive a variety of medications, some of which could modulate genomic damage levels and thus contribute to the observed heterogeneity. In addition, supplementation with vitamins or antioxidants may in some cases lower the genomic damage. Meta-Analysis confirmed the high and significant levels of genomic damage present in CKD patients compared to matched healthy controls. CONCLUSION: Genomic damage, as measured by the MN frequency, is elevated in CKD patients. Different strategies, including supplementation with antioxidants and optimizing dialysis processes, can reduce the levels of genomic damage and the different associated pathologies. Whether MN frequency can in the future also be used to assist in certain therapeutic decisions in CKD will have to be investigated further in larger studies.

Influence of Carnicor, Venofer, and Sevelamer on the levels of genotoxic damage in end-stage renal disease patients.

End-stage renal disease (ESRD) patients present high levels of phosphorus and calcium products in serum, which contribute to the development of vascular calcification and cardiovascular disease, and to low iron stores and carnitine deficiency. For these reasons, ESRD patients are generally supplemented with different medicines. Some of the most common treatments include the use of Carnicor, Venofer, and Sevelamer drugs. Carnicor is used as a source of L-carnitine, acting as antioxidant and neuroprotector. Venofer is used to reduce the deficit of iron. Sevelamer is used to treat hyperphosphatemia. To determine the potential harmful genotoxic effects of these drugs, a group of 214 patients included in a hemodialysis program with different intakes of Carnicor, Venofer, and Sevelamer were evaluated. The levels of basal and oxidative DNA damage, as well as chromosomal damage, were measured in all individuals using the comet and the micronucleus assays, respectively. Our results indicate that Carnicor administration was associated with low but significant increases in the frequency of basal DNA damage and micronuclei. Environ. Mol. Mutagen. 59:302-311, 2018. © 2018 Wiley Periodicals, Inc.

Unfermented grape juice reduce genomic damage on patients undergoing hemodialysis.

Chronic kidney disease (CKD) patients in dialysis (HD) are considered to be submitted to a continuous oxidative stress. This stress can cause damage on DNA and, consequently, contribute to the high levels of DNA damage observed in these patients. Due to the well-known role of polyphenols as antioxidant agents we proposed its use to reduce the levels of genotoxicity present in HD-CKD patients. The objective of this study was to evaluate the antigenotoxic effects of unfermented grape juice (UGJ) on HD-CKD patients. The levels of DNA damage were analyzed using different biomarkers, such as breaks and oxidized DNA bases by the comet assay, chromosome damage by the micronucleus test. In addition, TEAC (Trolox equivalent antioxidant capacity) was also evaluated. Thirty-nine patients were followed for six months, of whom 25 were supplemented by UGJ and 14 were not supplemented. The obtained results showed a significant decrease in the underlying levels of oxidative DNA damage, in the supplemented group. Regarding the clinical parameters, LDL and cholesterol, were significantly reduced in the patients studied after the supplementation period, although cholesterol was also decreased in the non-supplemented patients. In conclusion, in our studied group the supplementation with UGJ reduced the levels of oxidative DNA damage of HD-CKD patients.