Glucose degradation products in patients on hemodialysis. Interventional studies

Hemodialysis (HD) is the most frequently used treatment for end-stage renal disease. Despite all efforts to improve the outcomes, the mortality of patients on HD is still high, and this is especially related to cardiovascular diseases (CVD). Glucose degradation products accumulate in plasma and tissue; such accumulation is strongly related to the risk of developing CVD. Tissue deposits of advanced glycation end products (AGE) can be easily assessed by a skin autofluorescence (SAF) technique. This thesis examines if various interventions can reduce the load of AGE in HD patients. In Study 1 SAF and plasma fluorescence (PAF) were measured before and after a single HD in 35 patients on maintenance HD using glucose containing dialysate. A single HD did not change SAF, while PAF was reduced by 14%. Women had lower values than men. Study 2 investigated if there was a difference performing HD as in study 1 using high-flux (HF) versus low-flux (LF) dialyzers in 28 patients in a cross-over design. SAF was measured non-invasively before and after HD. Total and free/non-protein-bound PAF were measured. The different treatments did not change SAF either after LFor HF-HD. Total, free, and protein-bound PAF after a single HD were reduced but only to a limited amount by HD. The least effective was that on protein bound PAF using HF dialyzers in a setting using HD with glucose-containing dialysate. In Study 3 the effect on SAF was investigated using either glucose containing or glucose-free (GF) dialysate. SAF and PAF were measured in 24 HD patients with glucose-containing dialysate during standard treatment, and after 4 weeks switched over to a GF dialysate for a 2-week period. SAF decreased after a single HD using GF dialysate and was significant at the one-week measurement. This was the first evidence that a progressive increase in AGE deposition and consequently CVD could be hampered using GF dialysate. Protein bound PAF was best reduced with GF-HD. Study 4 investigated whether there was a seasonal variation in SAF in a HD population with special focus on the grilling season (June-August) since grilled foods contains more AGE than boiled foods. Skin-AF was measured before HD and at 4 times throughout 13 months. Unexpectedly there were seasonal variations in SAF with a 6% increase during the winter and a 11% reduction during the summer. Thus, a protective effect on SAF was found during the summer season. In conclusion, the studies indicate that GF-HD is preferable to limit AGE deposition and consequently CVD as determined indirectly by SAF values. The effect and variables of a summer season have a beneficial impact. Future studies of GF-HD, sun exposure and/or vitamin D are recommended.