Low-molecular but not high-molecular advanced glycation end products (AGEs) are removed by high-flux dialysis

<(Background)under bar>: Patients with end-stage renal disease (ESRD) displ ay very high levels of advanced glycation end products (AGEs). These compou nds an suspected to play a pathophysiological role in diabetic nephropathy and Late diabetic cardiovascular complications. We investigated to what ext ent AGE levels can be reduced by high-flux dialysis. <(Patients and methods )under bar>: Ten ESRD patients were treated three times each with DIAPES an d HF60, two different synthetic, high-flux hemodialysis membranes. The kine tics of AGE removal was studied by fluorescence spectroscopy (excitation 37 0 nm/emission 440 nm) and by ELISA of serum samples and the removal of beta (2)-m was studied by immunonephelometry of plasma samples. Samples were tak en during dialysis sessions at t = 0, 30 and 180 min. In addition, molecula r weight distribution of AGE products in serum of three patients was analyz ed by gel filtration and fluorescence detection. <(Results)under bar>: A si gnificant difference could be found when AGE levels in serum of controls (n = 10) were compared with serum AGE levels of ESRD patients (p < 0.01/fluor escence: p < 0.0001/ELISA). After 3 h of dialysis AGE-related fluorescence in serum decreased by 25.5 +/- 6.8% for HF60 (p < 0.0001) and 24.3 +/- 6.9% for DIAPES (p < 0.0001). The corresponding decline measured by ELISA was 2 3.3 +/- 8.9% for HF60 (p < 0.0001) and 26.1 +/- 7.0% for DIAPES (p < 0.0001 ). Both methods showed no significant differences for both types of dialysi s membranes. Gel filtration revealed that the decrease of fluorescence can be attributed to the removal of AGE peptides with a molecular mass < 12 kDa , only. Tn the high molecular range (> 12 kDa) no removal but hemoconcentra tion was observed independent. of the dialyzer type used. The reduction of beta(2)-m during 3 hours of dialysis was 61.8 +/- 6.9% for HF60 (p < 0.0001 ) and 161.7 +/- 7.0% for DIAPES (p < 0.0001). <(Conclusion)under bar>: Both high-flux dialyzers were equally effective to remove low-molecular AGE pro ducts, while AGE-modified proteins of higher molecular weight were only mar ginally affected. On the basis of our data we suggest the study of molecula r mass-dependent uremic toxicity of AGEs and the examination of the influen ce of other treatment modalities on the level of high-molecular AGEs.