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.

Longitudinal Study of Small Solute Transport and Peritoneal Protein Clearance in Peritoneal Dialysis Patients

“…The chief implication of this observation is what it adds to our understanding of the progressive changes to the membrane that occur over time. It supports a view that two processes are occurring-increased vascular surface area and progressive fibrosis-and that research should be done to identify biomarkers of this process (e.g., using the bioresource established for the Global Fluid Study [24]) and develop antifibrotic treatment strategies. There is potential to use this uncoupling as an easily-obtained clinical measurement to identify membrane change and monitor treatment interventions in the future.…”

Baseline Serum Interleukin-6 Predicts Cardiovascular Events in Incident Peritoneal Dialysis Patients

“…Nevertheless, in spite of biologic plausibility, the small effect size observed in our study is consistent with the possibility that the type of PD solution used has no major effect on the systemic inflammatory burden. Those (18). Furthermore, the rate of RRF loss made no significant impact on serum IL-6.…”

Higher Dialysate Matrix Metalloproteinase-2 Levels are Associated with Peritoneal Membrane Dysfunction

“…Fourth, inclusion of incident PD patients minimized the risk of Neyman bias; however, the duration of PD might have been too short to develop peritoneal membrane changes severe enough to detect difference in effect mediated by the use of biocompatible solutions. Fifth, dialysate interleukin-6 (IL-6), which has been recognized as the best predictor of PSTR to date from several studies including the GLOBAL study (27)(28)(29), has not been measured in the current cohort. Therefore, it is plausible that some of the results pertaining to MMP-2's ability to predict PSTR may in fact be driven by the presence of IL-6.…”