High Levels of Soluble C5b-9 Complex in Dialysis Fluid May Predict Poor Prognosis in Peritonitis in Peritoneal Dialysis Patients

Abstract

BackgroundWe searched for indicators to predict the prognosis of infectious peritonitis by measuring levels of complement proteins and activation products in peritoneal dialysis (PD) fluid (PDF) of patients at early stages of peritonitis. We retrospectively analyzed the relationship between the levels of sC5b-9, C3 and C4 in PDF and the subsequent clinical prognosis.MethodsWe measured levels of sC5b-9, C3 and C4 in PDF on days 1, 2 and 5 post-onset of peritonitis in 104 episodes of infectious peritonitis in PD patients from 2008 and retrospectively compared levels with clinical outcomes. Further analysis for the presence of causative microorganisms or to demonstrate bacterial culture negative peritonitis was performed and correlated with change of levels of sC5b-9 in PDF.ResultsWhen PD patients with peritonitis were divided into groups that either failed to recover from peritonitis and were finally withdrawn from PD (group 1; n = 25) or recovered (group 2; n = 79), levels of sC5b-9, C3 and C4 in PDF were significantly higher in group 1 patients compared to those in group 2 on day5. Analysis of microorganisms showed significantly higher sC5b-9 levels in PDF of peritonitis cases caused by culture negative peritonitis in group 1 compared with group 2 when we analyzed for individual microorganisms. Of note, on day5, the sC5b-9 levels in PDF were similarly high in peritonitis caused by fungi or other organisms.ConclusionOur results suggested that levels of complement markers in PDF, especially sC5b-9, have potential as surrogate markers to predict prognosis of PD-related peritonitis.

A Clinical Risk Prediction Tool for Peritonitis-Associated Treatment Failure in Peritoneal Dialysis Patients

“…Published studies suggest a promising role for novel biomarkers as risk predictors of adverse outcomes in patients with peritonitis 25 – 27 . Research in this field may yield information that can be incorporated into our predictive model to establish the prognostic value of these markers, primarily at the early presentation stage of PD-related peritonitis.…”

The Complement System in Dialysis: A Forgotten Story?

“…Complement activation products have also been suggested as a biomarker during peritonitis. Mizuno et al showed that C4, C3, and sC5b-9 levels in the peritoneal fluid are significantly higher in PD patients with poor prognosis after peritonitis ( 105 ). Complement markers in peritoneal fluid have, therefore, the potential to serve as a biomarker for the prediction of the prognosis of PD-related peritonitis.…”

Complement system activation and peritoneal membrane alterations: Culprit or innocent bystander?

“…Signs of complement and coagulation cascades activation were noted after exposure to PD fluids or in case of peritonitis, both in rat models but were also reduced after either complement or coagulation inhibition by anti-C5a molecule or low molecular weight heparin (LMWH), respectively, and inversely after enhanced complement activation. 19,51,52 However, few data on the coagulation system’s implication in PD are available and the relevance of coagulation and complement systems interconnection on various PD aspects still remains unknown. Still, human peritoneal mesothelial cells can produce several coagulation factors; among them, plasminogen activator inhibitor 1 could play a role in peritoneal membrane damage such as fibrosis and angiogenesis as well as peritonitis and EPS.…”

“…38,39,50 In a retrospective analysis, high levels of complement proteins, particularly C5b-9, in PD effluent of patients suffering from early stages of peritonitis were also associated with poor prognosis, defined as withdrawal from PD. 19 Although, it is still unclear whether increased complement activation is itself responsible for the poorer outcomes or if it is the signature of a more severe infection associated with a worse prognosis. On the other hand, it has also been proposed that reduced complement components levels due to intraperitoneal activation could impair host defense and thus increase the risk of peritonitis.…”