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.

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.

the snuffbox AV fistula gives a long segment of arterialised vein for needling and preserves proximal vessels. It is feasible in 50% of patients requiring primary access and has good long-term patency, especially in men. A more proximal fistula may be preferable in women with smaller vessels.

Accurate and timely diagnosis of bacterial infection is crucial for effective and targeted treatment, yet routine microbiological identification is inefficient and often delayed to an extent that makes it clinically unhelpful. The immune system is capable of a rapid, sensitive and specific detection of a broad spectrum of microbes, which has been optimized over millions of years of evolution. A patient's early immune response is therefore likely to provide far better insight into the true nature and severity of microbial infections than conventional tests. To assess the diagnostic potential of pathogen-specific immune responses, we characterized the local responses of 52 adult patients during episodes of acute peritoneal dialysis (PD)-associated peritonitis by multicolor flow cytometry and multiplex ELISA, and defined the immunologic signatures in relation to standard microbiological culture results and to clinical outcomes. We provide evidence that unique local "immune fingerprints" characteristic of individual organisms are evident in PD patients on the day of presentation with acute peritonitis and discriminate between culture-negative, Gram-positive, and Gram-negative episodes of infection. Those humoral and cellular parameters with the most promise for defining disease-specific immune fingerprints include the local levels of IL-1b, IL-10, IL-22, TNF-a, and CXCL10, as well as the frequency of local gd T cells and the relative proportion of neutrophils and monocytes/macrophages among total peritoneal cells. Our data provide proof of concept for the feasibility of using immune fingerprints to inform the design of point-of-care tests that will allow rapid and accurate infection identification and facilitate targeted antibiotic prescription and improved patient management.

The immune system has evolved to sense invading pathogens, control infection, and restore tissue integrity. Despite symptomatic variability in patients, unequivocal evidence that an individual's immune system distinguishes between different organisms and mounts an appropriate response is lacking. We here used a systematic approach to characterize responses to microbiologically well-defined infection in a total of 83 peritoneal dialysis patients on the day of presentation with acute peritonitis. A broad range of cellular and soluble parameters was determined in peritoneal effluents, covering the majority of local immune cells, inflammatory and regulatory cytokines and chemokines as well as tissue damage–related factors. Our analyses, utilizing machine-learning algorithms, demonstrate that different groups of bacteria induce qualitatively distinct local immune fingerprints, with specific biomarker signatures associated with Gram-negative and Gram-positive organisms, and with culture-negative episodes of unclear etiology. Even more, within the Gram-positive group, unique immune biomarker combinations identified streptococcal and non-streptococcal species including coagulase-negative Staphylococcus spp. These findings have diagnostic and prognostic implications by informing patient management and treatment choice at the point of care. Thus, our data establish the power of non-linear mathematical models to analyze complex biomedical datasets and highlight key pathways involved in pathogen-specific immune responses.

The antimicrobial responsiveness and function of unconventional human T cells are poorly understood, with only limited access to relevant specimens from sites of infection. Peritonitis is a common and serious complication in individuals with end-stage kidney disease receiving peritoneal dialysis. By analyzing local and systemic immune responses in peritoneal dialysis patients presenting with acute bacterial peritonitis and monitoring individuals before and during defined infectious episodes, our data show that Vγ9/Vδ2+ γδ T cells and mucosal-associated invariant T cells accumulate at the site of infection with organisms producing (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate and vitamin B2, respectively. Such unconventional human T cells are major producers of IFN-γ and TNF-α in response to these ligands that are shared by many microbial pathogens and affect the cells lining the peritoneal cavity by triggering local inflammation and inducing tissue remodeling with consequences for peritoneal membrane integrity. Our data uncover a crucial role for Vγ9/Vδ2 T cells and mucosal-associated invariant T cells in bacterial infection and suggest that they represent a useful predictive marker for important clinical outcomes, which may inform future stratification and patient management. These findings are likely to be applicable to other acute infections where local activation of unconventional T cells contributes to the antimicrobial inflammatory response.

BackgroundThe incidence of chronic kidney disease (CKD) is rising and is likely to continue to do so for the foreseeable future, with the fastest growth seen among adults ≥75 years of age. Elderly patients with advanced CKD are likely to have a higher burden of comorbidity and frailty, both of which may influence their disease outcome. For these patients, treatment decisions can be complex, with the current lack of robust prognostic tools hindering the shared decision-making process. The current study aims to assess the impact of comorbidity and frailty on the outcomes of patients referred for pre-dialysis education.MethodsWe performed a single-centre study of patients (n = 283) referred for pre-dialysis education between 2010 and 2012. The Charlson Comorbidity Index (CCI) and Clinical Frailty Scale (CFS) were used to assess comorbid disease burden and frailty, respectively. Follow-up data were collected until February 2015.ResultsThe CCI and CFS scores at the time of referral to the pre-dialysis service were independent predictors of mortality. Within the study follow-up period, 76% of patients with a high CFS score at the time of pre-dialysis education had died, with 63% of these patients not commencing dialysis before death.ConclusionA relatively simple frailty scale and comorbidity score could be used to predict survival and better inform the shared decision-making process for patients with advanced kidney disease.

This analysis supports observational data that changes in fluid status are associated with changes in urine volume. Icodextrin was not associated with a greater fall in urine output despite its larger effect on ECFv. Changes in fluid status could not be explained or did not appear to influence systemic inflammation. Nor can they be explained by individual variability in plasma concentrations of icodextrin that are in turn inversely proportional to the volume of distribution.