Measurement of innate immune response biomarkers in peritoneal dialysis effluent using a rapid diagnostic point-of-care device as a diagnostic indicator of peritonitis

Abstract

Peritonitis is the commonest complication of peritoneal dialysis and a major reason for treatment failure. Current diagnosis is based on clinical symptoms, cloudy effluent and a dialysate white cell count (over 100 cells/ml). A rapid point-of-care diagnostic test would accelerate diagnosis and potentially improve outcomes from infection. Here, in a clinical audit project, we used PERiPLEX â , a point-of-care device which detects when levels of matrix metalloproteinase-8 and interleukin-6 are elevated above a threshold within minutes in dialysis effluent, to assess whether it could confirm or exclude peritonitis in 107 patients undergoing peritoneal dialysis. Mean patient age was 64.6 years with a median duration of peritoneal dialysis of 13.3 months (interquartile range 6.3-33.5 months). Presence of peritonitis was confirmed by clinical criteria. There were 49 positive tests of which 41 patients had peritonitis, three had other causes of intra-peritoneal inflammation, three had severe urosepsis and two patients required no treatment. Fifty-eight tests were negative with one patient having a false negative result. The positive predictive value of the test was 83.7% (95% confidence interval 72.8-90.8) and the negative predictive value was 98.3% (89.1-99.8). Sensitivity and specificity were 97.6% (87.4-99.9) and 87.7% (77.2-94.5) respectively. Thus, PERiPLEX â could be used as a rapid point-of-care test that can aid the diagnosis or exclusion of peritonitis with a high negative predictive value.

Mechanisms of Peritoneal Fibrosis: Focus on Immune Cells–Peritoneal Stroma Interactions

“…The majority of peritonitis episodes in PD can be ascribed to Gram-positive bacteria of the skin and, to a minor degree, to Gram-negative bacteria presumably originating from the enteric flora ( 18 ).…”

“…Despite their mesodermal origin, MCs show a cobblestone morphology and actually coexpress in basal conditions epithelial and mesenchymal markers(51,59,81).MCs express tight and adherent junction related molecules such as ZO-1, occludin, claudins and E-cadherin, which is expressed both in plasma membrane and in cytoplasm(82). Moreover, these cells express epithelial intermediate filament proteins such as cytokeratins(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18) that play an important role in maintaining cellular structural integrity. At the same time, MCs constitutively express also mesenchymal intermediate filaments such as vimentin and desmin…”

CytoPy: an autonomous cytometry analysis framework

“…To validate CytoPy we demonstrate its use on the characterisation of immune cells in peritoneal drain fluid and whole blood of peritoneal dialysis (PD) patients with and without acute bacterial infection. We chose this dataset based on a wealth of previous experience in the field (25; 26; 27), the clinical relevance of acute peritonitis in those patients (28), and because of the technical challenges presented by the sample type. Samples were collected between 2017 and 2019 and stained with a comprehensive panel of monoclonal antibodies to identify T lymphocytes, monocytes, dendritic cells, eosinophils and neutrophils as the major constituents of peritoneal immune cells, together with activation and differentiation markers on those populations (Supplementary Tables S2 and S3).…”

Evaluation of a new rapid-diagnostic test for peritonitis in peritoneal dialysis: the PERIPLEX® device.

“…En utilisant des algorithmes auto-apprenants parmi 49 biomarqueurs testés lors de péritonites en dialyse péritonéale, MMP-8 s'est révélé dans le top 5 des biomarqueurs permettant de distinguer une péritonite bactérienne, d'une inflammation péritonéale stérile, ou d'une infection virale[14]. En cas d'inflammation systémique, IL-6 plasmatique augmente, et se retrouve dans le dialysat péritonéal après avoir franchi la membrane péritonéale[10,15,16]. En conséquence, il est possible qu'en l'absence de péritonite, une inflammation systémique positive le test PERIPLEX®.…”

“…Parmi les 12 faux-positifs constatés dans cette étude, 7 d'entre eux concernaient des situations de sepsis sans péritonite, ou d'inflammation péritonéale. Des résultats similaires ont été observés dans l'étude de Goodlab[10].CONCLUSIONCe nouveau test, basé sur la détection directe des biomarqueurs inflammatoires, est un test simple, fiable, rapide, réalisable par les patients eux-mêmes à leur domicile en cas de suspicion de péritonite. Les index statistiques d'évaluation de la valeur diagnostique du test sont excellents.…”