Plasma levels of advanced glycation end products during haemodialysis, haemodiafiltration and haemofiltration: potential importance of dialysate quality.

ABSTRACT

BACKGROUND: Advanced glycation end products (AGEs) accumulate in patients with end-stage renal disease (ESRD). The aim of this study was to investigate the potential influence of different modalities of renal replacement therapies on plasma AGE levels. METHODS: The removal of AGEs by high-flux haemodialysis (HD) using standard and ultrapure dialysis fluid (SDF and UDF), by haemodiafiltration (HDF) and by haemofiltration (HF) was studied by fluorescence spectroscopy and by a carboxymethyllysine (CML)-specific ELISA. In addition, molecular weight distribution of fluorescent AGE products in serum of several patients was analysed by gel filtration. RESULTS: The highest AGE-typical fluorescence was found in the serum of patients on HD using SDF (114,667+/-18,967 arbitrary units (AU)), followed by patients on HDF (86,912+/-24,411 AU, P<0.005), by patients on HD using UDF (74,953+/-21,152 AU, P<0.0001) and by patients on HF (74 039+/-17 027 AU, P<0.0001). Similar results were found for serum CML levels with the highest values in HD patients on SDF (1609+/-504 ng/ml), followed by patients on HF (1354+/-614 ng/ml, P<0.001), then by HD patients on UDF (1310+/-403 ng/ml, P<0.001) and by patients on HDF (1132+/-338 ng/ml, P<0.001). The removal rate of AGEs, as evaluated by the determination of the pre-/post-dialysis AGE differences, was comparable across all groups. CONCLUSION: These findings suggest that factors other than removal are responsible for the lower pre-dialysis AGE levels found in patients on convective dialysis as well as on HD with UDF. A role of water quality is assumed. This is corroborated by the finding that the high molecular weight AGE-fraction is preferentially lowered in comparison with patients on HD with SDF, as analysed by gel filtration chromatography. These findings could be best explained by a less severe oxidative stress (i.e. resulting in decreased AGE generation) with HF and HDF, as well as with ultrapure HD.