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Functional effector memory T cells enrich the peritoneal cavity of patients treated with peritoneal dialysis.

ABSTRACT: The frequency and severity of episodes of peritonitis adversely affect the structure and function of the peritoneal membrane in patients treated with peritoneal dialysis (PD), but the underlying mechanisms are not well understood. Alterations in the phenotype and function of resident peritoneal cells may contribute. Because effector memory T cells play a pivotal role in maintaining peripheral tissue immunity, we hypothesized that these cells may initiate or perpetuate the peritoneal inflammatory response. Here, we characterized the phenotype and effector function of peritoneal memory T cells. We found that functional effector memory T cells capable of mounting long-term recall responses enrich the peritoneal cavity of PD patients. Peritoneal T cells were able to mount a Th1-polarized response to recall antigens, and these responses were greater in peritoneal T cells compared with T cells in the peripheral blood. We also observed that the peritoneal T cells had altered telomeres; some cells had ultrashort telomeres, suggesting a highly differentiated local population. In summary, we describe a resident population of memory T cells in the peritoneum of PD patients and speculate that these cells form part of the first line of defense against invading pathogens.

SUBMITTER: Roberts GW

PROVIDER: S-EPMC2736769 | biostudies-literature | 2009 Sep

REPOSITORIES: biostudies-literature

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Functional effector memory T cells enrich the peritoneal cavity of patients treated with peritoneal dialysis.

Roberts Gareth W GW Baird Duncan D Gallagher Kathleen K Jones Rhiannon E RE Pepper Christopher J CJ Williams John D JD Topley Nicholas N

Journal of the American Society of Nephrology : JASN 20090827 9

The frequency and severity of episodes of peritonitis adversely affect the structure and function of the peritoneal membrane in patients treated with peritoneal dialysis (PD), but the underlying mechanisms are not well understood. Alterations in the phenotype and function of resident peritoneal cells may contribute. Because effector memory T cells play a pivotal role in maintaining peripheral tissue immunity, we hypothesized that these cells may initiate or perpetuate the peritoneal inflammatory ...[more]

PMID: 19713313

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Project description:BackgroundResults concerning the association between peritoneal dialysis-related peritonitis and mortality in peritoneal dialysis patients are inconclusive, with one potential reason being that the time-dependent effect of peritonitis has rarely been considered in previous studies. This study aimed to evaluate whether peritonitis has a negative impact on mortality in a large cohort of peritoneal dialysis patients. We also assessed the changing impact of peritonitis on patient mortality with respect to duration of follow-up.MethodsThis retrospective cohort study included incident patients who started peritoneal dialysis from 1 January 2006 to 31 December 2011. Episodes of peritonitis were recorded at the time of onset, and peritonitis was parameterized as a time-dependent variable for analysis. We used the Cox regression model to assess whether peritonitis has a negative impact on mortality.ResultsA total of 1321 patients were included. The mean age was 48.1 ± 15.3 years, 41.3% were female, and 23.5% with diabetes mellitus. The median (interquartile) follow-up time was 34 (21-48) months. After adjusting for confounders, peritonitis was independently associated with 95% increased risk of all-cause mortality (hazard ratio, 1.95; 95% confidence interval: 1.46-2.60), 90% increased risk of cardiovascular mortality (hazard ratio, 1.90; 95% confidence interval: 1.28-2.81) and near 4-fold increased risk of infection-related mortality (hazard ratio, 4.94; 95% confidence interval: 2.47-9.86). Further analyses showed that peritonitis was not significantly associated with mortality within 2 years of peritoneal dialysis initiation, but strongly influenced mortality in patients dialysed longer than 2 years.ConclusionsPeritonitis was independently associated with higher risk of all-cause, cardiovascular and infection-related mortality in peritoneal dialysis patients, and its impact on mortality was more significant in patients with longer peritoneal dialysis duration.

Project description:BackgroundExercise has been shown to be of benefit in the general population and in patients with chronic diseases. Despite a lack of compelling evidence, patients with end-stage kidney disease (ESKD) treated with peritoneal dialysis (PD) are often discouraged from participating in exercise programs that include weight lifting due to concerns about the development of hernias and leaks. The actual effects of physical activity with or without structured exercise programs for patients on PD remain unclear.ObjectiveTo determine the risks and benefits of physical activity in the ESKD population treated with PD.DesignSystematic review and meta-analysis.SettingIncluded all studies that met our criteria regardless of country of origin.PatientsAdult patients with ESKD treated with PD.MeasurementsDescriptive and quantitative analysis of our primary and secondary outcome variables.MethodsWe searched MEDLINE, Embase, CINAHL, and Cochrane Central Register of Controlled Trials for observational and interventional studies examining the effects of physical activity in patients on PD. A systematic review and meta-analysis was conducted of the identified studies. The primary outcomes of interest included patient-centered outcomes of mental health, physical functioning, fatigue, quality of life, and adverse events. Secondary outcomes included nutritional measures, lipid profile, blood pressure changes, maximum heart rate, resting heart rate, maximal oxygen consumption, muscle development, cognitive function, and markers of inflammation.ResultsOf 1828 studies identified by the literature search, 12 met the inclusion criteria including 6 interventional and 6 observational studies. There was limited information on the patient important outcomes. However, there is some evidence for improvements in burden of kidney disease, physical function, and some mental health measures with physical activity.LimitationsLack of well-designed randomized controlled trials impaired our ability to determine the benefits and risks of increasing physical activity.ConclusionsThere is limited evidence of benefit with increased levels of physical activity in PD patients. Further research is needed to define the exercise program that is likely to be of most benefit to patients treated with PD.

Project description:The prevalence of moderate to severe cognitive impairment in hemodialysis patients is more than double the prevalence in the general population. This study describes cognitive impairment occurrence in a peritoneal dialysis cohort compared with a cohort without chronic kidney disease (CKD).Cross-sectional study.51 English-speaking peritoneal dialysis patients from 2 urban dialysis units compared with 338 hemodialysis patients from 16 urban dialysis units and 101 voluntary controls without CKD from urban general medicine clinics.45-minute battery of 9 validated neuropsychological tests (cognitive domains memory, executive function, and language).Mild, moderate, or severe cognitive impairment, classified according to a previously designed algorithm.Of the peritoneal dialysis cohort, 33.3% had no or mild, 35.3% had moderate, and 31.4% had severe cognitive impairment; corresponding values were 60.4%, 26.7%, and 12.9% of the non-CKD cohort and 26.6%, 36.4%, and 37.0% of the hemodialysis cohort. A logistic regression model including age, sex, race, education, hemoglobin level, diabetes, and stroke showed that only nonwhite race (P = 0.002) and low education (P = 0.002) were associated with moderate to severe cognitive impairment in the peritoneal dialysis cohort. Compared with hemodialysis patients, more peritoneal dialysis patients had moderate to severe memory impairment (58% vs 51%), but fewer had impaired executive function (one-third vs one-half). Peritoneal dialysis was associated with a more than 2.5-fold increased risk of moderate to severe global cognitive impairment compared with no CKD (OR, 2.58; 95% CI, 1.02-6.53), as was hemodialysis (OR, 3.16; 95% CI, 1.91-5.24), in an adjusted logistic regression model.Small sample size, participation rate somewhat low.Similar to hemodialysis patients, two-thirds of peritoneal dialysis patients had moderate to severe cognitive impairment, enough to interfere with safely self-administering dialysis and adhering to complex medication regimens. These patients could benefit from cognitive assessment before and periodically after dialysis therapy initiation.

Project description:Unlabelled?BackgroundThe standard treatment of peritoneal dialysis (PD)-associated peritonitis (PD-peritonitis) is intraperitoneal (IP) administration of antibiotics. Only limited data on the pharmacokinetics and appropriateness of contemporary dose recommendations of IP cefalothin and cefazolin exist. The aim of this study was to describe the pharmacokinetics of IP cefalothin and cefazolin in patients treated for PD-peritonitis. ?MethodsAs per international guidelines, IP cefalothin or cefazolin 15 mg/kg once daily was dosed with gentamicin in a 6-hour dwell to patients with PD-peritonitis during routine care. Serial plasma and PD effluent samples were collected over the first 24 hours of therapy. Antibiotic concentrations were quantified using a validated chromatographic method with pharmacokinetic analysis performed using a non-compartmental approach. ?ResultsNineteen patients were included (cefalothin n = 8, cefazolin n = 11). The median bioavailability for both antibiotics exceeded 92%, but other pharmacokinetic parameters varied markedly between antibiotics. Both antibiotics achieved high PD effluent concentrations throughout the antibiotic dwell. Cefazolin had a smaller volume of distribution compared with cefalothin (14 vs 40 L, p = 0.003). The median trough total plasma antibiotic concentration for cefazolin and cefalothin during the dwell differed (plasma 56 vs 13 mg/L, p < 0.0001) despite a similar concentration in PD effluent (37 vs 38 mg/L, p = 0.58). Lower antibiotic concentrations were noted during PD dwells not containing antibiotic, particularly cefalothin, which was frequently undetectable in plasma and PD effluent. The median duration that the unbound antibiotic concentration was above the minimum inhibitory concentration (MIC) was approximately 13% (plasma) and 25% (IP) for cefalothin, and 100% (plasma and IP) for cefazolin, of the dosing interval. ?ConclusionsWhen IP cefalothin or cefazolin is allowed to dwell for 6 hours, sufficient PD effluent concentrations are present for common pathogens during this time. However, with once-daily IP dosing, in contrast to cefazolin, there is a risk of subtherapeutic plasma and PD effluent cefalothin concentrations, so more frequent dosing may be required.

Project description:BACKGROUND: Cardiovascular disease is a frequent cause of death in peritoneal dialysis patients. Biocompatible peritoneal dialysis solutions with neutral pH have been anticipated to reduce cardiovascular disease more than conventional peritoneal dialysis solutions with low pH, but it remains unclear which factors at peritoneal dialysis initiation increase cardiovascular risk in patients using biocompatible peritoneal dialysis solutions. This study was undertaken to investigate which clinical factors at peritoneal dialysis initiation, including peritoneal transport status, are associated with cardiovascular event in patients using biocompatible peritoneal dialysis solution. METHODS: This retrospective cohort study of peritoneal dialysis patients using biocompatible solutions with neutral pH assessed relations of clinical parameters at peritoneal dialysis initiation to cardiovascular event during the subsequent five years. RESULTS: Of 102 patients who started peritoneal dialysis, cardiovascular event occurred in 18. Age, history of cardiovascular disease before peritoneal dialysis initiation, hemoglobin, serum albumin, C-reactive protein, peritoneal permeability defined by the ratio of dialysate to plasma creatinine concentration at 4 hr (D/Pcre) in peritoneal equilibration test (PET), number of patients in each PET category defined by D/Pcre, and peritoneal protein clearance significantly differed between patients with and without cardiovascular event. For patients divided according to PET category using Kaplan-Meier method, the group of high average to high peritoneal transporters exhibited significantly high incidence of cardiovascular event and mortality compared with the groups of low and low-average peritoneal transporters (Log rank; p=0.0003 and 0.005, respectively). A Cox proportional hazards model showed independent association of PET category classification with cardiovascular event. CONCLUSIONS: Peritoneal permeability expressed as PET category at peritoneal dialysis initiation is an independent cardiovascular risk factor in peritoneal dialysis patients using biocompatible peritoneal dialysis solution with neutral pH. Greater peritoneal permeability at peritoneal dialysis initiation might reflect subclinical vascular disorders.

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Functional effector memory T cells enrich the peritoneal cavity of patients treated with peritoneal dialysis.

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Functional effector memory T cells enrich the peritoneal cavity of patients treated with peritoneal dialysis.

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