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.

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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