Dataset Information

Peritoneal macrophage heterogeneity is associated with different peritoneal dialysis outcomes.

ABSTRACT: Peritonitis remains the major obstacle for the maintenance of long-term peritoneal dialysis and dysregulated host peritoneal immune responses may compromise local anti-infectious defense, leading to treatment failure. Whilst, tissue mononuclear phagocytes, comprising macrophages and dendritic cells, are central to a host response to pathogens and the development of adaptive immune responses, they are poorly characterized in the human peritoneum. Combining flow cytometry with global transcriptome analysis, the phenotypic features and lineage identity of the major CD14⁺ macrophage and CD1c⁺ dendritic cell subsets in dialysis effluent were defined. Their functional specialization was reflected in cytokine generation, phagocytosis, and antigen processing/presentation. By analyzing acute bacterial peritonitis, stable (infection-free) and new-starter patients receiving peritoneal dialysis, we identified a skewed distribution of macrophage to dendritic cell subsets (increasing ratio) that associated with adverse peritonitis outcomes, history of multiple peritonitis episodes, and early catheter failure, respectively. Intriguingly, we also noted significant alterations of macrophage heterogeneity, indicative of different maturation and activation states that were associated with different peritoneal dialysis outcomes. Thus, our studies delineate peritoneal dendritic cells from macrophages within dialysate, and define cellular characteristics associated with peritoneal dialysis treatment failure. These are the first steps to unravelling the detrimental adaptive immune responses occurring as a consequence of peritonitis.

SUBMITTER: Liao CT

PROVIDER: S-EPMC5402633 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Peritoneal macrophage heterogeneity is associated with different peritoneal dialysis outcomes.

Liao Chia-Te CT Andrews Robert R Wallace Leah E LE Khan Mohd Wajid A MW Kift-Morgan Ann A Topley Nicholas N Fraser Donald J DJ Taylor Philip R PR

Kidney international 20170105 5

Peritonitis remains the major obstacle for the maintenance of long-term peritoneal dialysis and dysregulated host peritoneal immune responses may compromise local anti-infectious defense, leading to treatment failure. Whilst, tissue mononuclear phagocytes, comprising macrophages and dendritic cells, are central to a host response to pathogens and the development of adaptive immune responses, they are poorly characterized in the human peritoneum. Combining flow cytometry with global transcriptome ...[more]

PMID: 28065517

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Project description:BACKGROUND AND OBJECTIVES:Residual kidney function contributes to the clearance of antibiotics excreted by the kidneys, lowering the antibiotic concentration, which may adversely affect the treatment of peritoneal dialysis-associated peritonitis. The objective of our study was to examine the relationship between residual kidneyfunction and peritonitis treatment outcomes. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:Our study included 181 participants who experienced 339 episodes of Gram-positive, Gram-negative, and culture-negative peritoneal dialysis-associated peritonitis at a single centerfrom 2003 to 2010. Episodes were categorized according to participants' urinary creatinine clearance (0, >0-5, and >5 ml/min). The data were analyzed using generalized estimating equation models to determine the covariate-adjusted association between urinary creatinine clearance and treatment failure (defined as relapse or recurrent peritonitis episodes, peritoneal catheter removal, or death from any cause during peritonitis treatment). RESULTS:Among episodes of peritonitis due to Gram-positive organisms or culture-negative infections, those experienced by participants with urinary creatinine clearance >5 ml/min had significantly higher odds of treatment failure than episodes experienced by anuric participants (27 of 80 versus 20 of 119 episodes resulting in treatment failure for creatinine clearance >5 versus 0 ml/min; odds ratio, 6.80; 95% confidence interval, 2.37 to 19.6). Episodes experienced by participants with creatinine clearance >0-5 ml/min also had significantly higher odds of treatment failure than episodes experienced by anuric participants (14 of 64 episodes resulting in treatment failure for creatinine clearance >0-5 ml/min; odds ratio, 2.87; 95% confidence interval, 1.12 to 7.35). The odds of relapse and recurrent peritonitis among participants with creatinine clearance >5 ml/min was also significantly higher compared with in anuric participants (17 of 80 versus 12 of 119 episodes resulting in relapse and recurrence for creatinine clearance >5 versus 0 ml/min; odds ratio, 6.76; 95% confidence interval, 1.90 to 23.8). Among participants with Gram-negative peritonitis, creatinine clearance was significantly associated with neither treatment failure nor relapse and recurrent peritonitis. CONCLUSIONS:Residual kidney function as measured by greater urinary creatinine clearance was associated with treatment failure among participants with Gram-positive and culture-negative peritonitis.

Project description:Background and objectivesPeritoneal dialysis (PD) use increased in the United States with the introduction of a new Medicare prospective payment system in January 2011 that likely reduced financial disincentives for facility use of this home therapy. The expansion of PD to a broader population and facilities having less PD experience may have implications for patient outcomes. We assessed the impact of PD expansion on PD discontinuation and patient mortality.Design, setting, participants, & measurementsA prospective cohort study was conducted of patients treated with PD at 90 days of ESKD. Patients were grouped by study start date relative to the Medicare payment reform: prereform (July 1, 2008 to December 31, 2009; n=10,585), interim (January 1, 2010 to December 31, 2010; n=7832), and reform period (January 1, 2011 to December 31, 2012; n=18,742). Patient characteristics and facility PD experience were compared at baseline (day 91 of ESKD). Patients were followed for 3 years for the major outcomes of PD discontinuation and mortality using Cox proportional hazards models.ResultsPatient characteristics, including age, sex, race, ethnicity, rurality, cause of ESKD, and comorbidity, were similar or showed small changes across the three study periods. There was an increasing tendency for patients on PD to be treated in facilities with less PD experience (from 34% during the prereform period being treated in facilities averaging <14 patients on PD per year to 44% in the reform period). Patients treated in facilities with less PD experience had a higher rate of PD discontinuation than patients treated in facilities with the most experience (hazard ratio [HR], 1.16; 95% confidence interval [95% CI], 1.10 to 1.23 for the first versus fifth quintile of PD experience). Nevertheless, the risk of PD discontinuation fell during the late interim period (HR, 0.88; 95% CI, 0.82 to 0.95) and most of the reform period (from HR, 0.85; 95% CI, 0.79 to 0.91 to HR, 0.94; 95% CI, 0.87 to 1.01). Mortality risk was stable across the three study periods.ConclusionsIn the context of expanding PD use and declining facility PD experience, the risk of PD discontinuation fell, and there was no adverse effect on mortality.PodcastThis article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2019_09_12_CJN01610219.mp3.

Project description:Dialysis prolongs life but augments cardiovascular mortality. Imaging data suggests that dialysis increases myocardial blood flow (BF) heterogeneity, but its causes remain poorly understood. A biophysical model of human coronary vasculature was used to explain the imaging observations, and highlight causes of coronary BF heterogeneity. Post-dialysis CT images from patients under control, pharmacological stress (adenosine), therapy (cooled dialysate), and adenosine and cooled dialysate conditions were obtained. The data presented disparate phenotypes. To dissect vascular mechanisms, a 3D human vasculature model based on known experimental coronary morphometry and a space filling algorithm was implemented. Steady state simulations were performed to investigate the effects of altered aortic pressure and blood vessel diameters on myocardial BF heterogeneity. Imaging showed that stress and therapy potentially increased mean and total BF, while reducing heterogeneity. BF histograms of one patient showed multi-modality. Using the model, it was found that total coronary BF increased as coronary perfusion pressure was increased. BF heterogeneity was differentially affected by large or small vessel blocking. BF heterogeneity was found to be inversely related to small blood vessel diameters. Simulation of large artery stenosis indicates that BF became heterogeneous (increase relative dispersion) and gave multi-modal histograms. The total transmural BF as well as transmural BF heterogeneity reduced due to large artery stenosis, generating large patches of very low BF regions downstream. Blocking of arteries at various orders showed that blocking larger arteries results in multi-modal BF histograms and large patches of low BF, whereas smaller artery blocking results in augmented relative dispersion and fractal dimension. Transmural heterogeneity was also affected. Finally, the effects of augmented aortic pressure in the presence of blood vessel blocking shows differential effects on BF heterogeneity as well as transmural BF. Improved aortic blood pressure may improve total BF. Stress and therapy may be effective if they dilate small vessels. A potential cause for the observed complex BF distributions (multi-modal BF histograms) may indicate existing large vessel stenosis. The intuitive BF heterogeneity methods used can be readily used in clinical studies. Further development of the model and methods will permit personalized assessment of patient BF status.

Dataset Information

Peritoneal macrophage heterogeneity is associated with different peritoneal dialysis outcomes.

Publications

Peritoneal macrophage heterogeneity is associated with different peritoneal dialysis outcomes.

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