BACKGROUND: Patients with end-stage renal disease (ESRD) display very high levels of advanced glycation end products (AGEs). These compounds are suspected to play a pathophysiological role in diabetic nephropathy and late diabetic cardiovascular complications. We investigated to what extent AGE levels can be reduced by high-flux dialysis. PATIENTS AND METHODS: Ten ESRD patients were treated three times each with DIAPES and HF60, two different synthetic, high-flux hemodialysis membranes. The kinetics of AGE removal was studied by fluorescence spectroscopy (excitation 370 nm/ emission 440 nm) and by ELISA of serum samples and the removal of beta2-m was studied by immunonephelometry of plasma samples. Samples were taken during dialysis sessions at t = 0, 30 and 180 min. In addition, molecular weight distribution of AGE products in serum of three patients was analyzed by gel filtration and fluorescence detection. RESULTS: A significant 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/fluorescence; 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% tor DIAPES (p < 0.0001). The corresponding decline measured by ELISA was 23.3 +/- 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 dialysis 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. In the high molecular range (> 12 kDa) no removal but hemoconcentration was observed independent of the dialyzer type used. The reduction of beta2-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: Both high-flux dialyzers were equally effective to remove low-molecular AGE products, while AGE-modified proteins of higher molecular weight were only marginally affected. On the basis of our data we suggest the study of molecular mass-dependent uremic toxicity of AGEs and the examination of the influence of other treatment modalities on the level of high-molecular AGEs.
BACKGROUND:Patients with end-stage renal disease (ESRD) display very high levels of advanced glycation end products (AGEs). These compounds are suspected to play a pathophysiological role in diabetic nephropathy and late diabetic cardiovascular complications. We investigated to what extent AGE levels can be reduced by high-flux dialysis. PATIENTS AND METHODS: Ten ESRDpatients were treated three times each with DIAPES and HF60, two different synthetic, high-flux hemodialysis membranes. The kinetics of AGE removal was studied by fluorescence spectroscopy (excitation 370 nm/ emission 440 nm) and by ELISA of serum samples and the removal of beta2-m was studied by immunonephelometry of plasma samples. Samples were taken during dialysis sessions at t = 0, 30 and 180 min. In addition, molecular weight distribution of AGE products in serum of three patients was analyzed by gel filtration and fluorescence detection. RESULTS: A significant difference could be found when AGE levels in serum of controls (n = 10) were compared with serum AGE levels of ESRDpatients (p < 0.01/fluorescence; 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% tor DIAPES (p < 0.0001). The corresponding decline measured by ELISA was 23.3 +/- 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 dialysis 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. In the high molecular range (> 12 kDa) no removal but hemoconcentration was observed independent of the dialyzer type used. The reduction of beta2-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: Both high-flux dialyzers were equally effective to remove low-molecular AGE products, while AGE-modified proteins of higher molecular weight were only marginally affected. On the basis of our data we suggest the study of molecular mass-dependent uremic toxicity of AGEs and the examination of the influence of other treatment modalities on the level of high-molecular AGEs.
Authors: Andréa E M Stinghen; Ziad A Massy; Helen Vlassara; Gary E Striker; Agnès Boullier Journal: J Am Soc Nephrol Date: 2015-08-26 Impact factor: 10.121
Authors: April C E van Gennip; Natascha J H Broers; Karlien J Ter Meulen; Bernard Canaud; Maarten H L Christiaans; Tom Cornelis; Mariëlle A C J Gelens; Marc M H Hermans; Constantijn J A M Konings; Jeroen B van der Net; Frank M van der Sande; Casper G Schalkwijk; Frank Stifft; Joris J J M Wirtz; Jeroen P Kooman; Remy J H Martens Journal: PLoS One Date: 2019-09-13 Impact factor: 3.240