OBJECTIVE: Patients with end-stage renal disease (ESRD) exhibit an enhanced genomic damage which may have pathophysiological relevance for cancer development and cardiovascular complications. The DNA damage has been shown both in the pre-dialysis and dialysis phase by micronucleus (MN) frequency test and single cell gel electrophoresis in peripheral blood lymphocytes (PBLs). A major cause of DNA damage is oxidative stress, which may be induced by various uremic toxins, including advanced glycation end products (AGEs), as well as by activation of the renin-angiotensin system. RESULTS: Genomic damage of ESRD patients can be ameliorated by daily hemodialysis (DHD), as observed in a cross-sectional study. Patients on DHD showed a reduced genomic damage in the MN frequency test in PBLs compared to those treated with standard hemodialysis. Another way to decrease DNA damage in ESRF seems to be the chronic administration of angiotensin II type 1 (AT)1 receptor blockers. In 15 maintenance hemodialysis patients, treatment with candesartan resulted in a significant improvement of DNA damage. According to our in vitro data, these beneficial effects may be a consequence of preventing the genotoxic actions of angiotensin II. Vitamin B1 (benfotiamine) was found to be able to reduce the amount of circulating AGEs in animal experiments. We could show in a pilot study that the application of benfotiamine significantly reduced the genomic damage of dialysis patients. CONCLUSION: There are several possibilities of lowering genomic damage in dialysis patients, which in the long run might lead to lower cancer incidences.
OBJECTIVE:Patients with end-stage renal disease (ESRD) exhibit an enhanced genomic damage which may have pathophysiological relevance for cancer development and cardiovascular complications. The DNA damage has been shown both in the pre-dialysis and dialysis phase by micronucleus (MN) frequency test and single cell gel electrophoresis in peripheral blood lymphocytes (PBLs). A major cause of DNA damage is oxidative stress, which may be induced by various uremic toxins, including advanced glycation end products (AGEs), as well as by activation of the renin-angiotensin system. RESULTS: Genomic damage of ESRDpatients can be ameliorated by daily hemodialysis (DHD), as observed in a cross-sectional study. Patients on DHD showed a reduced genomic damage in the MN frequency test in PBLs compared to those treated with standard hemodialysis. Another way to decrease DNA damage in ESRF seems to be the chronic administration of angiotensin II type 1 (AT)1 receptor blockers. In 15 maintenance hemodialysis patients, treatment with candesartan resulted in a significant improvement of DNA damage. According to our in vitro data, these beneficial effects may be a consequence of preventing the genotoxic actions of angiotensin II. Vitamin B1 (benfotiamine) was found to be able to reduce the amount of circulating AGEs in animal experiments. We could show in a pilot study that the application of benfotiamine significantly reduced the genomic damage of dialysis patients. CONCLUSION: There are several possibilities of lowering genomic damage in dialysis patients, which in the long run might lead to lower cancer incidences.