Genetic damage in chronic renal failure patients is associated with the glomerular filtration rate index.

Chronic renal failure (CRF) patients are considered to present genomic instability and, as a consequence, elevated levels of genetic damage. An open question is whether this damage is related to the stage of the pathology. To determine the background levels of genetic damage, a large population of 258 Caucasian adults (201 CRF patients and 57 controls) was analysed using the micronucleus (MN) assay. The frequency of MN in CRF patients was significantly higher than in controls and correlated with the progression of the disease, according to the glomerular filtration rate. In addition, a significant association was observed between genetic damage and serum creatinine levels. Genetic damage, measured as frequency of MN, increases when renal function decreases. The fact that an increased level of MN is already observed in patients' Stage 2 seems to indicate a genetic predisposition on these patients. Nevertheless, part of the observed damage can be attributed to the uraemic state itself.

Oxidative DNA damage in chronic renal failure patients.

BACKGROUND: Chronic renal failure (CRF) patients present a high incidence of cardiovascular pathologies and cancer. This has been attributed to the existence of genomic instability in these patients, and consequently they should present elevated levels of genetic damage. METHODS: To determine the background levels of genetic damage and its specific levels of oxidative damage, a large population of 253 CRF patients (77 in dialysis) was analysed using the comet assay. The percentage of DNA in the tail was used as a measure of basal genetic damage. In addition, the use of endo III and FPG enzymes allowed us to determine the levels of specific oxidative damage in DNA bases. RESULTS: This is the first study that uses endo III and FPG enzymes to measure oxidative damage in CRF patients. Overall genetic damage, as well as specific oxidative damage, was higher in dialysis patients than in the CRF patients with different stages of uraemic state; genetic damage increased when serum creatinine levels increased. Genomic damage in dialysis patients decreased in those patients submitted to dialysis for a long time. CONCLUSIONS: Genetic damage increases when renal function decreases, being maximum in haemodialysis patients. Although part of the observed damage can be attributed to the uraemic state itself, other individual genetic factors can influence a state of genomic instability responsible for the observed genomic damage.