Low glucose degradation product peritoneal dialysis regimen is associated with lower plasma EN-RAGE and HMGB-1 proinflammatory ligands of receptor for advanced glycation end products

Abstract

Intraperitoneal glucose degradation products (GDP) load influences systemic advanced glycation end products (AGEs) but the effects on soluble receptor for AGEs (s-RAGE) and its proinflammatory ligands: extracellular newly identified receptor for advanced glycation end-products binding protein(EN-RAGE) and high mobility group box-1 protein (HMGB-1) are unknown. We aimed to compare plasma and peritoneal s-RAGE, EN-RAGE and HMGB-1 between three peritoneal dialysis (PD) prescription regimens with different intraperitoneal GDP loads. High GDP load (glucose-lactate PD fluid, D; N = 8) was compared with a low (glucose-bicarbonate/lactate with icodextrin for overnight dwell, E; N = 9) and a very low GDP load (glucose-bicarbonate/lactate, P; N = 16). D group demonstrated higher plasma EN-RAGE, 77.8 ng/mL, vs. both E, 11.2, P < 0.001 and P, 27.0, P < 0.001 as well as higher plasma HMGB-1, 2.2 ng/mL vs. both E, 1.1, P < 0.01 and P, 1.5, P < 0.01. Plasma s-RAGE, which did not differ between D, E and P, correlated with its effluent levels. Patients with faster peritoneal transport (D/Pcr > 0.65) tended to have higher plasma s-RAGE compared to slow transporters (2300 vs. 1762 pg/mL, P = 0.056). Peritoneal clearance of s-RAGE and EN-RAGE was higher with E compared to both D and P (P < 0.001 resp. P < 0.01). Subgroup of PD patients with CRP above median demonstrated higher plasma HMGB-1 and EN-RAGE, P < 0.05 for both. A lower intraperitoneal GDP load is associated with decreased plasma levels of EN-RAGE and HMGB-1. Peritoneal transport, microinflammation and the capability of icodextrin to increase peritoneal clearance of middle molecular weight substances might also exert an effect on plasma s-RAGE and its proinflammatory ligands levels.

Keywords: Advanced glycation end products; Extracellular newly identified receptor for advanced glycation end products-binding protein; High mobility group box-1 protein; Peritoneal dialysis; Receptor for advanced glycation end products.