Effects of Icodextrin and Glucose Bicarbonate/Lactate-Buffered Peritoneal Dialysis Fluids on Effluent Cell Population and Biocompatibility Markers IL-6 and CA125 in Incident Peritoneal Dialysis Patients.

Icodextrin peritoneal dialysis (PD) solution has been shown to increase interleukin-6 (IL-6) levels in PD effluent as well as leukocyte and mesothelial cell count. Mesothelial cells release cancer antigen 125 (CA125), which is used as a marker of mesothelial cell mass. This 1-year prospective study was designed to compare peritoneal effluent cell population, its inflammatory phenotype and biocompatibility biomarkers IL-6 and CA125 between icodextrin (E) and glucose bicarbonate/lactate (P) based PD solutions. Using baseline peritoneal ultrafiltration capacity, 19 stable incident PD patients were allocated either to P only (N = 8) or to P plus E for the overnight dwell (N = 11). Flow cytometry was used to measure white blood cell count and differential and the expression of inflammatory molecules on peritoneal cells isolated from timed overnight peritoneal effluents. Compared to P, E effluent showed higher leukocyte (10.9 vs. 7.9), macrophages (6.1 vs. 2.5) and mesothelial cells (0.3 vs. 0.1)×10(6) /L count, as well as expression of HLA DR on mesothelial cells and IL-6 (320.5 vs. 141.2 pg/min) on mesothelial cells and CA125 appearance rate (159.6 vs. 84.3 IU/min), all P < 0.05. In the E group, correlation between IL-6 and CA125 effluent levels (r = 0.503, P < 0.05) as well as appearance rates (r = 0.774, P < 0.001) was demonstrated. No effect on systemic inflammatory markers or peritoneal permeability was found. Icodextrin PD solution activates local inflammation without systemic consequences so the clinical relevance of this observation remains obscure. Correlation between effluent IL-6 and CA125 suggests that CA125 might be upregulated due to inflammation and thus is not a reliable marker of mesothelial cell mass and/or biocompatibility.

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.

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.