Genomic Damage and Malignancy in End-Stage Renal Failure: Do Advanced Glycation End Products Contribute?

Abstract

In end-stage renal disease (ESRD) there is not only excessive morbidity and mortality due to cardiovascular disease but also an enhanced occurrence of various types of cancer. Both are characterized by oxidative stress and inflammation as two of the central underlying causes of the disease states. In cancer, genomic damage has been demonstrated to be of high pathogenetic relevance. DNA lesions may induce mutations of oncogenes and tumor-suppressor genes which, in the long-run, may lead to malignancies if mutagenicity is not mitigated by repair mechanisms. A high incidence of genomic damage in ESRD patients has been validated by various biomarkers of DNA lesions. We reviewed the mechanisms of DNA damage, focusing in particular on the role of advanced glycation end products (AGEs) which accumulate markedly in renal insufficiency. Considering the in vitro and in vivo findings to date, one has to assume a significant role of AGEs in DNA damage and the potential development of cancer.

Hepatocyte growth factor prevents advanced glycation end products-induced injury and oxidative stress through a PI3K/Akt-dependent pathway in human endothelial cells

“…ROS promote formation of AGEs, which cause AGEreceptor-mediated ROS generation with activation of signaling pathways leading to tissue injury and further AGEs accumulation. AGEs have been demonstrated to interact with specific receptors and induce oxidative stress, enhance vascular cell adhesion molecule-1 expression, and increase endothelial adhesiveness for monocytes (Sebeková et al 2007). Our observations demonstrated that AGEs resulted in a significant overproduction of ROS in HUVECs.…”

Oxidative Stress and Nucleic Acid Oxidation in Patients with Chronic Kidney Disease

“…Oxidative stress and inflammation have been demonstrated to be of high pathogenetic relevance to cancer, especially because of the contribution of genomic damage. Oxidative damage to DNA may cause mutations of oncogenes and tumor-suppressor genes and may represent one mechanism underlying carcinogenesis [119–121]. AGEs are thought to be genotoxic.…”

Immune Dysfunction in Uremia—An Update

“…Dialysis treatment, per se , is a potential source of damage and may be responsible for the T-cell specific immunodeficiency correlated with uremia [190]. DNA damage by AGEs may also be important in the development of several forms of cancer, a disease with increased occurrence in CKD patients [191]. …”