Abstract. The European APD Outcome Study (EAPOS) is a 2-yr, prospective, multicenter study of the feasibility and clinical outcomes of automated peritoneal dialysis (APD) in anuric patients. A total of 177 patients were enrolled with a median age of 54 yr (range, 21 to 91 yr). Previous median total time on dialysis was 38 mo (range, 1.6 to 259 mo), and 36% of patients had previously been on hemodialysis for Ͼ90 d. Diabetes and cardiovascular disease were present in 17% and 46% of patients, respectively. The APD prescription was adjusted at physician discretion to aim for creatinine clearance (Ccrea) Ն60 L/wk per 1.73 m 2 and ultrafiltration (UF) Ն750 ml/24 h during the first 6 mo. Baseline solute transport status (D/P) was determined by peritoneal equilibration test. At 1 yr, 78% and 74% achieved Ccrea and UF targets, respectively; median drained dialysate volume was 16.2 L/24 h with 50% of patients using icodextrin. Baseline D/P was not related to UF achieved at 1 yr. At 2 yr, patient survival was 78% and technique survival was 62%. Baseline predictors of poor survival were age (Ͼ65 yr; P ϭ 0.006), nutritional status (Subjective Global Assessment grade C; P ϭ 0.009), diabetic status (P ϭ 0.008), and UF (Ͻ750 ml/24 h; P ϭ 0.047). Time-averaged analyses showed that age, Subjective Global Assessment grade C and diabetic status predicted patient survival with UF the next most significant variable (risk ratio, 0.5/L per d; P ϭ 0.097). Baseline Ccrea, time-averaged Ccrea, and baseline D/P had no effect on patient or technique survival. This study shows that anuric patients can successfully use APD. Baseline UF, not Ccrea or membrane permeability, is associated with patient survival.

Technical innovations in peritoneal dialysis (PD), now used widely for the long-term treatment of ESRD, have significantly reduced therapy-related complications, allowing patients to be maintained on PD for longer periods. Indeed, the survival rate for patients treated with PD is now equivalent to that with in-center hemodialysis. In parallel, changes in public policy have spurred an unprecedented expansion in the use of PD in many parts of the world. Meanwhile, our improved understanding of the molecular mechanisms involved in solute and water transport across the peritoneum and of the pathobiology of structural and functional changes in the peritoneum with long-term PD has provided new targets for improving efficiency and for intervention. As with hemodialysis, almost half of all deaths on PD occur because of cardiovascular events, and there is great interest in identifying modality-specific factors contributing to these events. Notably, tremendous progress has been made in developing interventions that substantially reduce the risk of PD-related peritonitis. Yet the gains have been unequal among individual centers, primarily because of unequal clinical application of knowledge gained from research. The work to date has further highlighted the areas in need of innovation as we continue to strive to improve the health and outcomes of patients treated with PD.

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Several studies of long-term PD in the literature now complement each other in providing a picture of what really happens to PD patients. The links between loss of solute clearance and poor peritoneal ultrafiltration combining to exacerbate sudden or debilitated death and technique failure are emerging. For PD to be successful as a long-term therapy, strategies that maintain nutrition and preserve peritoneal membrane function must be developed.

Comorbidity has a quantitative effect on survival that is independent of age, RRF and membrane function in PD patients. Comorbidity also appears to be associated with increased solute transport at the start of treatment, which is sustained. With the exception of diabetes, grade of comorbidity does not have a profound effect on loss of RRF.

Bioimpedance analysis (BIA) derives two main pieces of information--total tissue fluid content, which when referring to the whole patient is equivalent to the total body water (TBW), and cell mass, which in the limbs mainly reflects muscle. The relationship between these measures, expressed in different ways, is abnormal in dialysis patients due to muscle wasting combined with tissue overhydration. In both dialysis modalities this is associated with aging, comorbidity, and inflammation, and there is a conflict between achieving euvolemia to improve blood pressure control and prevent left ventricular hypertrophy on one hand, but risking episodes of hypovolemia and loss of residual renal function on the other. In peritoneal dialysis, the situation is exacerbated by hypoalbuminemia, whereas in hemodialysis BIA is unable to distinguish between the plasma volume and tissue edema components of interdialytic weight gain. In longitudinal studies BIA can identify changes in hydration following a defined intervention, and spontaneous loss in TBW consequent on muscle wasting not appreciated clinically, resulting in a failure to sufficiently reduce the dry weight. Cardiac biomarkers provide additional information but it is not clear whether this reflects fluid status or underlying structural organ damage. Intervention studies are now needed that show how this information is best used to improve patient outcomes, including meaningful end points such as hospitalization and survival.

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.

Abstract. Worsening fluid balance results in reduced technique and patient survival in peritoneal dialysis. Under these conditions, the glucose polymer icodextrin is known to enhance ultrafiltration in the long dwell. A multicenter, randomized, double-blind, controlled trial was undertaken to compare icodextrin versus 2.27% glucose to establish whether icodextrin improves fluid status. Fifty patients with urine output Ͻ750 ml/d, high solute transport, and either treated hypertension or untreated BP Ͼ140/90 mmHg, or a requirement for the equivalent of all 2.27% glucose exchanges, were randomized 1:1 and evaluated at 1, 3, and 6 mo. Members of the icodextrin group lost weight, whereas the control group gained weight. Similar differences in total body water were observed, largely explained by reduced extracellular fluid volume in those receiving icodextrin, who also achieved better ultrafiltration and total sodium losses at 3 mo (P Ͻ 0.05) and had better maintenance of urine volume at 6 mo (P ϭ 0.039). In patients fulfilling the study's inclusion criteria, the use of icodextrin, when compared with 2.27% glucose, in the long exchange improves fluid removal and status in peritoneal dialysis. This effect is apparent within 1 mo of commencement and was sustained for 6 mo without harmful effects on residual renal function.