title: 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 inflammation with regards to peritoneal membrane 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 peritoneal membrane function. Dialysate and plasma cytokines were measured 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 networks were 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 inflammation was the most important determinant of PSTR but did not affect survival. In prevalent patients, the relationship between local inflammation and membrane function persisted but did not account for an increased mortality associated with faster PSTR. These data suggest that systemic and local intraperitoneal inflammation reflect distinct processes and consequences in patients treated with peritoneal dialysis, so their prevention may require different therapeutic approaches; the significance of intraperitoneal inflammation requires further elucidation.
authors.affiliation: Institute for Science and Technology in Medicine, Keele University, Stoke on Trent, United Kingdom;
authors.forename: Mark
authors.initials: M
authors.lastname: Lambie
authors.forename: James
authors.initials: J
authors.lastname: Chess
authors.forename: Kieron L
authors.initials: KL
authors.lastname: Donovan
authors.forename: Yong Lim
authors.initials: YL
authors.lastname: Kim
authors.forename: Jun Young
authors.initials: JY
authors.lastname: Do
authors.forename: Hi Bahl
authors.initials: HB
authors.lastname: Lee
authors.forename: Hyunjin
authors.initials: H
authors.lastname: Noh
authors.forename: Paul F
authors.initials: PF
authors.lastname: Williams
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Williams
authors.forename: Sara
authors.initials: S
authors.lastname: Davison
authors.forename: Marc
authors.initials: M
authors.lastname: Dorval
authors.forename: Angela
authors.initials: A
authors.lastname: Summers
authors.forename: John D
authors.initials: JD
authors.lastname: Williams
authors.forename: John
authors.initials: J
authors.lastname: Bankart
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Davies
authors.forename: Nicholas
authors.initials: N
authors.lastname: Topley
mesh_terms: D000328:Adult; D000368:Aged; D015331:Cohort Studies; D015897:Comorbidity; D016207:Cytokines / Q000097:blood / Q000276:immunology; D005260:Female; D006801:Humans; D015994:Incidence; D007249:Inflammation / Q000276:immunology / Q000401:mortality*; D007676:Kidney Failure, Chronic / Q000401:mortality* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010530:Peritoneal Dialysis / Q000401:mortality*; D010537:Peritoneum / Q000276:immunology; D010538:Peritonitis / Q000276:immunology / Q000401:mortality*; D011237:Predictive Value of Tests; D015995:Prevalence
chemical_list: D016207:Cytokines