Genomic damage and circulating AGE levels in patients undergoing daily versus standard haemodialysis

Background. Patients with end-stage renal failure, whether on conservative or haemodialysis therapy, have a high incidence of DNA damage. It is not known if improved control of the uraemic state by daily haemodialysis (DHD) reduces DNA lesions. Methods. DNA damage in peripheral blood lymphocytes (PBLs) was evaluated in a cross-sectional study of 13 patients on DHD (2-3 h, 6 times/week), 12 patients on standard haemodialysis (SHD) therapy (4-5 h, 3 times/week) and 12 healthy age-matched volunteer controls. The biomarker of DNA damage used was micronucleus frequency. The assessed plasma parameters of microinflammation and oxidative stress were C-reactive protein (CRP), interleukin-6 (IL-6), neopterin, advanced oxidation protein products (AOPP), and homocysteine. We also measured plasma concentrations of the circulating advanced glycation end products (AGEs) MGI (methylglyoxal-derived imidazolinone), CML (carboxymethyllysine), imidazolone A (3-deoxyglucosone-derived imidazolinone) and AGE-associated fluorescence. Results. Compared to SHD, DHD was associated with significantly lower DNA damage, approaching the normal range. Micronuclei (MN) frequency averaged 29.1 MN +/- 5.9/1000 binucleated (BN) cells in the SHD group, which is significantly elevated (P < 0.01), 14.8 MN +/- 4.0/1000 BN cells in the DHD group, and 13.2 MN +/- 3.04/1000 BN cells in the controls. CRP and AOPP were in the normal range (and similar between the dialysis groups). In contrast, IL-6 and neopterin were significantly elevated, with lower values associated with DHD as compared with SHD. The increased levels of AGEs tended to be lower in the DHD group, reaching significance for CML and imidazolone A. Conclusions. Overall, it was found that genomic damage in PBLs is lower in patients on DHD than in those on SHD. Lower plasma concentrations of uraemic toxins, including circulating AGEs, may account for the differences. To confirm these data, prospective clinical trials need to be performed.