DNA Damage in Chronic Kidney Disease: Evaluation of Clinical Biomarkers

Abstract

Patients with chronic kidney disease (CKD) exhibit an increased cancer risk compared to a healthy control population. To be able to estimate the cancer risk of the patients and to assess the impact of interventional therapies thereon, it is of particular interest to measure the patients' burden of genomic damage. Chromosomal abnormalities, reduced DNA repair, and DNA lesions were found indeed in cells of patients with CKD. Biomarkers for DNA damage measurable in easily accessible cells like peripheral blood lymphocytes are chromosomal aberrations, structural DNA lesions, and oxidatively modified DNA bases. In this review the most common methods quantifying the three parameters mentioned above, the cytokinesis-block micronucleus assay, the comet assay, and the quantification of 8-oxo-7,8-dihydro-2′-deoxyguanosine, are evaluated concerning the feasibility of the analysis and regarding the marker's potential to predict clinical outcomes.

Association between urologic malignancies and end‐stage renal disease: A meta‐analysis

“…11,12 In addition, recent evidence has also suggested that patients with CKD and ESRD have deoxyribonucleic acid (DNA) damage and impaired DNA repair, potentially leading to an increased cancer risk. 45 In our meta-analysis, we demonstrated that the incidence of kidney cancer was 0.4% in ESRD patients, which is significantly higher than the currently reported incidence (approximately 0.005%) in the general population. 5 While the association between ESRD and urothelial cancers could be hypothesized as ACKD related, we lack a clear understanding for the high incidence of urothelial cancers in the ESRD population.…”

“…Regardless of its association with renal function, ACKD is a known risk factor for kidney cancer . In addition, recent evidence has also suggested that patients with CKD and ESRD have deoxyribonucleic acid (DNA) damage and impaired DNA repair, potentially leading to an increased cancer risk . In our meta‐analysis, we demonstrated that the incidence of kidney cancer was 0.4% in ESRD patients, which is significantly higher than the currently reported incidence (approximately 0.005%) in the general population …”

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

“…It is well known that CKD patients present an elevated incidence of different types of cancer (mainly cervical, bladder, thyroid, and renal), as well as cardiovascular pathologies (Di Angelantonio et al, 2010;Stengel, 2010). With regard to the comet assay this has been demonstrated to be a potent tool in human biomonitoring studies (Collins et al, 2014), and it has been already used to evaluate genetic damage levels in CKD patients (Corredor et al, 2015;Schupp et al, 2015;Mamur et al, 2016). Previous studies have demonstrated increased levels of DNA damage and genomic instability in CKD patients (Sandoval et al, , 2012Stoyanova et al, 2010Stoyanova et al, , 2014Rodr ıguez-Ribera et al, 2014).…”

“…It must be remembered that the frequency of MN is considered one of the best and most reliable biomarkers to detect genotoxic agents (Kirsch-Volders et al, 2014), and it has been widely used for the study of chronic renal failure patients (Roth et al, 2008;Sandoval et al, 2012;Rodr ıguez-Ribera et al, 2014). With regard to the comet assay this has been demonstrated to be a potent tool in human biomonitoring studies , and it has been already used to evaluate genetic damage levels in CKD patients (Corredor et al, 2015;Schupp et al, 2015;Mamur et al, 2016).…”

The Cycle of Kinetochore-Negative Micronuclei and Chromosome Fragments Occurred in Mitosis of Hela Cells

“…Elevated frequencies of MNi are also found in patients with cancer and other diseases [3,4]. MNi are formed from an entire chromosome or from a chromosomal fragment.…”