SummaryFibrosis in response to tissue damage or persistent inflammation is a pathological hallmark of many chronic degenerative diseases. By using a model of acute peritoneal inflammation, we have examined how repeated inflammatory activation promotes fibrotic tissue injury. In this context, fibrosis was strictly dependent on interleukin-6 (IL-6). Repeat inflammation induced IL-6-mediated T helper 1 (Th1) cell effector commitment and the emergence of STAT1 (signal transducer and activator of transcription-1) activity within the peritoneal membrane. Fibrosis was not observed in mice lacking interferon-γ (IFN-γ), STAT1, or RAG-1. Here, IFN-γ and STAT1 signaling disrupted the turnover of extracellular matrix by metalloproteases. Whereas IL-6-deficient mice resisted fibrosis, transfer of polarized Th1 cells or inhibition of MMP activity reversed this outcome. Thus, IL-6 causes compromised tissue repair by shifting acute inflammation into a more chronic profibrotic state through induction of Th1 cell responses as a consequence of recurrent inflammation.

Box 1 | Prevailing attitudes of medical professionals emerging from public review and participant survey Agreement with goal of standardizing nomenclature, with acknowledgment of challenges Regarded multiplicity of terms and lack of adherence to established definitions as confusing and potentially leading to errors Anticipated that a standardized nomenclature would help foster consistency in trial design, execution, and reporting Judged consistency between terms used in scholarly and patient communities to be an important goal, but not one overriding the need for precision and efficiency Journal editors strongly agreed that having a more standardized nomenclature for kidney disease would be useful for their journals, but they anticipated time constraints of journal personnel to be the biggest barrier to implementation Qualified endorsement of replacing "renal" with "kidney" Felt that foregrounding "kidney" would be easier for patients and their families Perceived a greater likelihood of raising awareness, attracting funding, and influencing public policy with consistent use of "kidney" Cautioned against a wholesale switch because "renal" may be less awkward in some contexts and may be necessary in others (e.g., ESRD as a CMS definition) Dissatisfaction with "end-stage" as a descriptor of kidney disease Recognized that this wording can be demoralizing and stigmatizing for patients Considered the implication of imminent death to be outdated Frustrated by imprecision in its use (ranging from being a synonym for dialysis patients to a descriptor of patients with kidney failure with or without kidney replacement therapy) Recognition of the need for ongoing attention to nomenclature issues Noted that standardization of nomenclature is dependent on uptake of consensus definitions B where definitions are in flux or are more contentious, standardization of that nomenclature set may be premature B enhancing adoption of definitions requires continued effort Highlighted the need for harmonization with ongoing, broader-scope ontology efforts Expected that improved understanding of molecular mechanisms will lead to more-precise definitions and nomenclature CMS, Centers for Medicare & Medicaid Services; ESRD, end-stage renal disease.

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.

3. To reach a consensus that should be given to nephrologists and their patients about the length of time that is advisable to remain on PD. GUIDELINES FOR EPSGuidelines on the topic of EPS have been issued by the Japanese Society for Peritoneal Dialysis (8), the UK Renal Association (9), and the Dutch EPS Registry (10). When reading the guidelines, it is clear that issuing evidence-based guidelines on EPS is being hampered by: