Genomic instability in chronic renal failure patients

Abstract

Patients suffering chronic renal failure (CRF) exhibit a high incidence of cancer, as well as high levels of genetic damage. We hypothesized that these patients show genomic instability as measured by increased radiosensitivity to the induction of genetic damage. The background levels of genetic damage and the net genetic damage after in vitro irradiation with 0.5 Gy were analyzed using the micronucleus assay in peripheral blood lymphocytes of 174 CRF patients and 53 controls. The net radiation-induced genetic damage was significantly higher in CRF patients with respect to controls. Among CRF patients, the levels of genetic damage were higher in those with prior incidence of cancer than in those without cancer; in addition, those CRF patients undergoing hemodialysis presented with higher levels of genetic damage than those in the advanced Stages (4-5) of the pathology. A positive association was observed between basal and net micronucleus frequency among CFR patients. However, no association was found between net genetic damage and parameters linked to the different stages of the pathology, such as urine creatinine levels and glomerular filtration rate. Our results indicate that CRF patients show increased radiosensitivity and that the degree of radiosensitivity is associated with the progression of the pathological stage of the disease.

Genomic instability in patients with autosomal-dominant polycystic kidney disease

“…This hypothesis is consistent with data from patients with chronic renal failure that demonstrated an inverse relationship between renal function and genomic instability. 16 It is known that age, smoking, and physical and chemical assaults are directly associated with genomic stability. 17 Older people have increased apoptosis and basal DNA damage, and are more sensitive to the effects of oxidative damage and g-irradiation.…”

Genomic damage as a biomarker of chronic kidney disease status

“…Therefore, increased levels of DNA damage in the general population could be considered as indicative of a potential risk of developing CKD, as well as other pathologies. This may be a consequence of the genomic instability demonstrated in these patients, who presented a poor response to repair damage induced in their DNA [Sandoval et al, ]. This genomic instability has also been observed when telomere length, considered a classical biomarker of genomic instability, was used.…”

“…In addition to the increased cancer incidence, it has been demonstrated that CKD patients show genomic instability [Sandoval et al, 2012]. In an open literature search, we found 41 studies published between 1988 and 2013 showing that CKD patients present higher levels of DNA damage than controls.…”

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

“…To evaluate the radiosensitivity of the patients, as a measure of genomic instability, lymphocytes were irradiated at a dose of 0.5 Gy at the Unitat Tècnica de Protecci o Radiol ogica (UTPR-UAB) as already published (Sandoval et al, 2012). Irradiated cultures followed the same protocol as described before.…”

“…Especially important are the potential effects on the levels of DNA damage that could be generated. 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). This increased cancer risk is independent of symptom severity or whether they are undergoing dialysis.…”