Amadori Albumin and Advanced Glycation End-Product Formation in Peritoneal Dialysis using Icodextrin

Abstract

To study the influence of peritoneal dialysis (PD) solutions on the formation of early glycated products and advanced glycation end-products (AGEs). The formation of both Amadori albumin and AGEs in glucose- and icodextrin-based PD fluids was analyzed in vitro and in peritoneal effluents of continuous cyclic peritoneal dialysis (CCPD) patients. Albumin incubated with glucose-based PD fluids showed a time- and glucose concentration-dependent formation of Amadori albumin and AGEs. Aminoguanidine completely inhibited AGE but not Amadori albumin formation. Albumin incubated in icodextrin resulted in the lowest levels of Amadori albumin and AGE. Amadori albumin levels in effluents of 24 CCPD patients (12 glucose and 12 icodextrin for their daytime dwells) were similar. Dialysate samples collected during a mass transfer area coefficient test in 16 CCPD patients (8 glucose, 8 icodextrin) showed an increase in Amadori albumin formation from baseline (p < 0.0001), without a difference between the groups. In the total group, there was a positive relationship between duration on PD and dialysate Amadori albumin concentration at 240 minutes (p = 0.03). The Amadori albumin dialysate-to-plasma (D/P) ratio at 240 minutes was 0.82+/-0.11, and its clearance amounted to 7.71+/-1.14 mL/min, while the albumin D/P ratio was 0.010+/-0.003 and its clearance was 0.089+/-0.017 mL/min. In a peritoneal biopsy of a CCPD patient, Amadori albumin was observed in the mesothelial layer and the endothelium of the peritoneum. Using icodextrin-based instead of glucose-based PD fluids can largely reduce the formation of Amadori albumin and AGEs. However, CCPD patients using icodextrin during daytime dwells do not have lower effluent levels of Amadori albumin and AGEs, probably due to the exposure to glucose during their nighttime exchanges. Kinetic studies suggest washout of locally produced Amadori albumin.