Relation between different treatment modalities and genomic damage of end-stage renal failure patients.
BACKGROUND
Patients with end-stage renal disease display enhanced genomic damage. We investigated the relation between genomic damage and different treatment modalities.


METHODS
In a longitudinal study two groups of patients were analyzed in monthly intervals. We assessed the initiation of hemodialysis in 5 conservatively treated patients, and a switch from hemodialysis to hemodiafiltration in 7 patients. DNA damage was investigated in peripheral blood lymphocytes by micronucleus frequency and by comet assay analysis. With regard to potential genotoxicity of advanced glycation end products (AGEs), levels of imidazolone A and AGE-associated fluorescence (AGE-FL) were determined.


RESULTS
The initiation of hemodialysis did not alter the genomic damage. In patients who switched from hemodialysis to hemodiafiltration, a small but significant reduction in the comet assay but not in the micronucleus frequency was observed. Elevated plasma levels of imidazolone A and AGE-FL were not influenced by the treatment modalities.


CONCLUSIONS
In our small patient group no major reduction of the elevated genomic damage could be reached. Disease factors not influenced by altered dialysis modalities may have contributed considerably in our patient group. The persisting high levels of DNA damage suggest a need for further improvement. Inhibiting AGE formation may be one promising way for the future.
Institute of Pharmacology and Toxicology, University of Würzburg, Würzburg, Germany.
K
K
Kobras
N
N
Schupp
K
K
Nehrlich
M
M
Adelhardt
U
U
Bahner
J
J
Vienken
A
A
Heidland
K
K
Sebekova
H
H
Stopper
D000368:Aged; D020552:Comet Assay; D004249:DNA Damage; D015894:Genome, Human; D017127:Glycation End Products, Advanced / Q000097:blood; D017583:Hemodiafiltration; D006801:Humans; D007093:Imidazoles / Q000097:blood; D007676:Kidney Failure, Chronic / Q000235:genetics* / Q000628:therapy*; D008137:Longitudinal Studies; D008214:Lymphocytes / Q000502:physiology; D008297:Male; D048629:Micronuclei, Chromosome-Defective; D008875:Middle Aged; D006435:Renal Dialysis; D016896:Treatment Outcome; D014511:Uremia / Q000235:genetics / Q000628:therapy
D017127:Glycation End Products, Advanced; D007093:Imidazoles; C117197:imidazolone