The roles of complement factor C5a and CINC-1 in glucose transport, ultrafiltration, and neutrophil recruitment during peritoneal dialysis

Abstract

◆ Background: In a recent experimental study, we showed that low molecular weight heparin improved ultrafiltration and blocked complement activation and coagulation in a single peritoneal dialysis (PD) dwell. ◆ Objective: The aim of the present study was to evaluate the possible contribution of the complement factor C5a and the potential interactions between C5a, the coagulation system, and cytokines of the interleukin (IL)-8 family (cytokine-induced neutrophil chemoattractant; CINC-1). ◆ Methods: Nonuremic rats were exposed through an in-dwelling catheter to a single dose of 20 mL glucose- (2.5%) based fifter-sterilized PD fluid, with or without the addition of anti-rat CS antibody. The dwell fluid was analyzed 2 and 4 hours later concerning activation of the coagulation cascades, neutrophil recruitment, ultrafiltration volume; CINC-1, glucose, urea, and histamine concentrations; and ex vivo intraperitoneal chemotactic activity. ◆ Results: The numbers of neutrophils and levels of thrombin-antithrombin complex (TAT) and CINC-1 increased significantly during the PD dwell. C5 blockade significantly reduced the levels of TAT and increased the ultrafiltration volumes at 2 hours. Glucose concentrations were significantly positively correlated to ultrafiltration volumes. ◆ Conclusions: Blockade of C5 Leads to an increase in ultrafiltration, probably by a mechanism that involves a reduction in glucose transport. This effect may form a basis for improving PD efficiency in situations where high glucose transport limits ultrafiltration. Mechanisms connected to complement activation during PD may involve coagulation. Further studies of the intraperitoneal cascade systems under conditions of PD are indicated. Copyright © 2006 International Society for Peritoneal Dialysis.