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.