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.

Figure 1.

Graph of dialysate-to-plasma (D/P) concentration ratio (y-axis) for IL-6 concentrations. The line represents the ratio predicted by the three-pore model (0.145), so all points above this line are predicted to represent local production, which occurs in the majority of patients (87%).

Figure 2.

Scatterplot of PSTR measured as 4-hour dialysate-to-plasma creatinine ratio with dialysate IL-6 demonstrating a center effect. Each line represents a center-specific linear regression slope. Dialysate IL-6 is measured on a logarithmic scale. Despite the center effects seen for many of the measurements in GLOBAL the correlation between dialysate IL-6 and PSTR was always observed.