Independent effects of systemic and peritoneal inflammation on peritoneal dialysis survival

Abstract

Systemic inflammation, as evidenced by elevated inflammatory cytokines, is a feature of advanced renal failure and predicts worse survival. Dialysate IL-6 concentrations associate with variability in peritoneal small solute transport rate (PSTR), which has also been linked to patient survival. Here, we determined the link between systemic and intraperitoneal inflammationwith regards to peritonealmembrane function and patient survival as part of the Global Fluid Study, a multinational, multicenter, prospective, combined incident and prevalent cohort study (n=959 patients) with up to 8 years of follow-up. Data collected included patient demographic characteristics, comorbidity,modality, dialysis prescription, and peritonealmembrane function. Dialysate and plasma cytokinesweremeasured by electrochemiluminescence. A total of 426 survival endpoints occurred in 559 incident and 358 prevalent patients from 10 centers in Korea Canada, and the United Kingdom. On patient entry to the study, systemic and intraperitoneal cytokine networkswere dissociated,with evidence of local cytokine production within the peritoneum. After adjustment for multiple covariates, systemic inflammation was associated with age and comorbidity and independently predicted patient survival in both incident and prevalent cohorts. In contrast, intraperitoneal inflammationwas themost important determinant of PSTR but did not affect survival. In prevalent patients, the relationship between local inflammation andmembrane function persisted but did not account for an increased mortality associated with faster PSTR. These data suggest that systemic and local intraperitoneal inflammation reflect distinctprocesses and consequences in patients treated with peritoneal dialysis, so their preventionmay require different therapeutic approaches; the significance of intraperitoneal inflammation requires further elucidation. Copyright © 2013 by the American Society of Nephrology.