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      High Levels of Soluble C5b-9 Complex in Dialysis Fluid May Predict Poor Prognosis in Peritonitis in Peritoneal Dialysis Patients

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          Abstract

          Background

          We searched for indicators to predict the prognosis of infectious peritonitis by measuring levels of complement proteins and activation products in peritoneal dialysis (PD) fluid (PDF) of patients at early stages of peritonitis. We retrospectively analyzed the relationship between the levels of sC5b-9, C3 and C4 in PDF and the subsequent clinical prognosis.

          Methods

          We measured levels of sC5b-9, C3 and C4 in PDF on days 1, 2 and 5 post-onset of peritonitis in 104 episodes of infectious peritonitis in PD patients from 2008 and retrospectively compared levels with clinical outcomes. Further analysis for the presence of causative microorganisms or to demonstrate bacterial culture negative peritonitis was performed and correlated with change of levels of sC5b-9 in PDF.

          Results

          When PD patients with peritonitis were divided into groups that either failed to recover from peritonitis and were finally withdrawn from PD (group 1; n = 25) or recovered (group 2; n = 79), levels of sC5b-9, C3 and C4 in PDF were significantly higher in group 1 patients compared to those in group 2 on day5. Analysis of microorganisms showed significantly higher sC5b-9 levels in PDF of peritonitis cases caused by culture negative peritonitis in group 1 compared with group 2 when we analyzed for individual microorganisms. Of note, on day5, the sC5b-9 levels in PDF were similarly high in peritonitis caused by fungi or other organisms.

          Conclusion

          Our results suggested that levels of complement markers in PDF, especially sC5b-9, have potential as surrogate markers to predict prognosis of PD-related peritonitis.

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          Most cited references15

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          Peritonitis remains the major clinical complication of peritoneal dialysis: the London, UK, peritonitis audit 2002-2003.

          Over the past two decades, the rate of peritonitis in patients treated by peritoneal dialysis (PD) has been significantly reduced. However, peritonitis remains a major complication of PD, accounting for considerable mortality and hospitalization among PD patients. To compare the outcome of peritonitis in a large unselected group of PD patients with that from single-center and selected groups. We audited the outcome of peritonitis in PD patients attending the 12 PD units in the Thames area in 2002 and 2003. There were 538 patients on continuous ambulatory PD (CAPD) and 325 patients on automated PD (APD) and/or continuous cycling PD (CCPD) at the end of 2002, and 635 CAPD and 445 APD/CCPD patients at the end of 2003. There were 1467 episodes of PD peritonitis during the 2-year period, including 129 recurrent episodes, with the average number of months between peritonitis episodes being 14.7 for CAPD and 18.1 for APD/CCPD, p < 0.05. However there was considerable variation between units. Coagulase-negative staphylococcus (CoNS) was the most common cause, accounting for around 30% of all peritonitis episodes, including recurrences, followed by non-pseudomonas gram negatives and Staphylococcus aureus. Cure rates were 77.2% for CoNS, 46.6% for S. aureus, and 7.7% for methicillin-resistant S. aureus. The cure rate for pseudomonas was 21.4%, and other gram negatives 56.7%. In total, there were 351 episodes of culture-negative peritonitis, with an average cure rate of 76.9%. Cure rates were higher for those centers that used a combination of intraperitoneal gentamicin and cephalosporins than those centers that used oral-based regimes. A total of 296 PD catheters were removed as a direct consequence of PD peritonitis: 121 due to gram-positive and 123 due to gram-negative organisms. Only 49 catheters were reinserted and the patients returned to PD. 52 patients died during or subsequent to their episode of PD peritonitis, with an overall mortality rate of 3.5%. This audit showed that, in a large unselected population of PD patients, the incidence of peritonitis was significantly greater than that reported in single-center short-term studies, and varied from unit to unit. Similarly, the success of treating PD peritonitis varied not only with the cause of the infection but also from unit to unit. PD peritonitis remains a major cause of patients discontinuing PD and switching to hemodialysis.
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            CARD-FISH for Environmental Microorganisms: Technical Advancement and Future Applications

            Fluorescence in situ hybridization (FISH) has become a standard technique in environmental microbiology. More than 20 years have passed since this technique was first described, and it is currently used for the detection of ribosomal RNA, messenger RNA, and functional genes encoded on chromosomes. This review focuses on the advancement and applications of FISH combined with catalyzed reporter deposition (CARD, also known as tyramide signal amplification or TSA), in the detection of environmental microorganisms. Significant methodological improvements have been made in CARD-FISH technology, including its combination with other techniques and instruments.
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              Predictive value of dialysate cell counts in peritonitis complicating peritoneal dialysis.

              Early prediction of outcomes has major potential implications regarding the management of dialysis-related peritonitis. The outcomes of 565 consecutive episodes of peritonitis complicating peritoneal dialysis between August 2001 and July 2005 were evaluated in relation to the dialysate cell counts. Discriminatory power, based on the area under the receiver-operating characteristic (ROC) curves, of the cell counts was assessed. The findings then were validated externally in a cohort of 217 peritonitis episodes from another dialysis unit. During the study period, 565 episodes of peritonitis were included for analysis, 465 of which had treatment success defined as complete resolution of peritonitis without the need for Tenckhoff catheter removal. Of the remaining 100 episodes (treatment failure), 70 required Tenckhoff catheter removal and 30 had peritonitis-related death. The peritoneal dialysate total white blood cell count on day 3 of peritonitis predicted treatment failure independent of standard risk factors, and it had a higher area under the ROC curve than the dialysate white cell count on day 1 (0.80 versus 0.58; P or = 1090/mm3 on day 3, the sensitivity was 75% and the specificity was 74% for the prediction of treatment failure (defined as catheter loss or peritonitis-related death). In multiple logistic regression analyses, peritoneal dialysate white count > or = 1090/mm3 on day 3 was an independent prognostic marker for treatment failure after adjustment for conventional risk factors (hazard ratio 9.03; 95% confidence interval 4.40 to 18.6; P < 0.0001). Number of years on peritoneal dialysis; diabetes; gram-negative organisms; and Pseudomonas, fungal, or Mycobacterium species were other independent risk factors that were predictive of treatment failure. Findings from an independent validation set of peritonitis (217 episodes after exclusion of Mycobacterium and fungal causes) also favored the peritoneal dialysate white count on day 3, as compared with day 1 and day 2, to predict treatment failure. Area under the ROC curve for the white counts on day 3 was 0.98 (95% confidence interval 0.95 to 0.99) in the validation set. This study demonstrated and cross-validated the superiority of peritoneal dialysate white cell count on day 3 to predict outcomes of dialysis-related peritonitis. These results call attention to the value of validating prognostic factors of peritonitis complicating peritoneal dialysis.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                3 January 2017
                2017
                : 12
                : 1
                : e0169111
                Affiliations
                [1 ]Renal Replacement Therapy, Nagoya University Graduate School of Medicine, Nagoya, Japan
                [2 ]Division of Nephrology, Nagoya University Graduate School of Medicine, Nagoya, Japan
                [3 ]Daiyukai-daiichi Hospital, Ichinomiya, Japan
                [4 ]Complement Biology Group, Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, United Kingdom
                University of Leicester, UNITED KINGDOM
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                • Conceptualization: MM S. Matsuo BPM.

                • Data curation: MM DI.

                • Formal analysis: MM DI FS.

                • Funding acquisition: MM BPM S. Matsuo.

                • Investigation: MM Y. Sei KH FS YI.

                • Methodology: MM S. Maruyama MH.

                • Resources: MM Y. Suzuki MH YI.

                • Validation: MM DI.

                • Writing – original draft: MM BPM.

                • Writing – review & editing: MM BPM.

                Article
                PONE-D-16-25974
                10.1371/journal.pone.0169111
                5207753
                28046064
                b2994b05-930e-4dd2-9bce-c33c14019d83
                © 2017 Mizuno et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 29 June 2016
                : 12 December 2016
                Page count
                Figures: 7, Tables: 3, Pages: 18
                Funding
                Funded by: the Ministry of Education, Culture, Sports, Science and Technology in Japan Grants-in-Aid
                Award ID: 24591227 and 15K09288
                Award Recipient :
                Funded by: a research grant of the Japanese association for complement research
                Award Recipient :
                Funded by: the research grants from the Japanese association of dialysis physician
                Award ID: JADP Grants 2012-07 and 2014-03
                Award Recipient :
                Funded by: a Ministry of Health, Labour and Welfare of Japan grant-in-aid for Progressive Renal Diseases Research, Research on Rare and Intractable Disease
                Award Recipient :
                Funded by: the Great Britain Sasakawa Foundation 2015 Butterfield Award for UK-Japan collaboration in Medicine and Health
                Award ID: B90
                Award Recipient :
                Funded by: the Great Britain Sasakawa Foundation 2015 Butterfield Award for UK-Japan collaboration in Medicine and Health
                Award ID: B90
                Award Recipient :
                This work was in part supported in part by the Ministry of Education, Culture, Sports, Science and Technology in Japan Grants-in-Aid 24591227 and 15K09288 for Scientific Research, by a research grant of the Japanese association for complement research, by the research grants from Japanese association of dialysis physician (JADP Grants 2012-07 and 2014-03), by a Ministry of Health, Labour and Welfare of Japan grant-in-aid for Progressive Renal Diseases Research, Research on Rare and Intractable Disease, and by the Great Britain Sasakawa Foundation 2015 Butterfield Award for UK-Japan collaboration in Medicine & Health to Mizuno M and Morgan BP (No. B90). Mizuno M, Suzuki Y and Ito Y worked in the Department of Renal Replacement Therapy as positions endowed by Baxter Japan at Nagoya University Graduate School of Medicine. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Medicine and Health Sciences
                Diagnostic Medicine
                Signs and Symptoms
                Peritonitis
                Medicine and Health Sciences
                Pathology and Laboratory Medicine
                Signs and Symptoms
                Peritonitis
                Medicine and Health Sciences
                Diagnostic Medicine
                Prognosis
                Biology and Life Sciences
                Microbiology
                Bacteriology
                Gram Positive Bacteria
                Biology and Life Sciences
                Anatomy
                Abdomen
                Peritoneum
                Medicine and Health Sciences
                Anatomy
                Abdomen
                Peritoneum
                Biology and Life Sciences
                Microbiology
                Bacteriology
                Gram Negative Bacteria
                Biology and Life Sciences
                Organisms
                Fungi
                Medicine and Health Sciences
                Infectious Diseases
                Fungal Diseases
                Medicine and Health Sciences
                Nephrology
                Medical Dialysis
                Custom metadata
                All relevant data are within the paper and its raw data are attached as a supplementary table ( S1 Table).

                Uncategorized
                Uncategorized

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