Abstract
Infection remains a major cause of morbidity, mortality and technique failure in patients with end stage kidney failure who receive peritoneal dialysis (PD). Recent research suggests that the early inflammatory response at the site of infection carries diagnostically relevant information, suggesting that organ and pathogen-specific “immune fingerprints” may guide targeted treatment decisions and allow patient stratification and risk prediction at the point of care. Here, we recorded microRNA profiles in the PD effluent of patients presenting with symptoms of acute peritonitis and show that elevated peritoneal miR-223 and reduced miR-31 levels were useful predictors of bacterial infection. Cell culture experiments indicated that miR-223 was predominantly produced by infiltrating immune cells (neutrophils, monocytes), while miR-31 was mainly derived from the local tissue (mesothelial cells, fibroblasts). miR-223 was found to be functionally stabilised in PD effluent from peritonitis patients, with a proportion likely to be incorporated into neutrophil-derived exosomes. Our study demonstrates that microRNAs are useful biomarkers of bacterial infection in PD-related peritonitis and have the potential to contribute to disease-specific immune fingerprints. Exosome-encapsulated microRNAs may have a functional role in intercellular communication between immune cells responding to the infection and the local tissue, to help clear the infection, resolve the inflammation and restore homeostasis.
Highlights
Peritoneal dialysis (PD) is an effective and life-saving renal replacement therapy for approximately 250,000 patients with end stage kidney failure worldwide[1]
Our findings shows that miR-223 in particular is a promising biomarker that is produced by neutrophils, increased in acute peritonitis, and associated with extracellular vesicles in infected peritoneal dialysis (PD) effluent
Effluent samples from three different groups of individuals receiving PD were investigated: uninfected stable patients who had not experienced an episode of peritonitis for at least 3 months prior to recruitment into this study, and those presenting with acute peritonitis that was subsequently confirmed by microbiological culture as infection by either coagulase-negative Staphylococcus (CNS) or E. coli
Summary
Peritoneal dialysis (PD) is an effective and life-saving renal replacement therapy for approximately 250,000 patients with end stage kidney failure worldwide[1]. In the absence of rapid and reliable diagnostic tests at the point of care, patients typically receive an empirical first-line treatment of broad-spectrum antibiotics, long before culture results become available and prescription can be tailored toward the causative organism[2] This delay in giving the most appropriate treatment to patients, combined with the exposure to drugs that are not needed, adds to inflammation-related damage, avoidable drug-specific side effects, unnecessary health care costs and the ever-increasing emergence of multidrug resistant microbes[3]. Despite the unmet need to provide early and targeted therapy, no major improvements in the diagnosis of PD-related peritonitis have been implemented in the clinic[1,4] This is even more surprising given the landmark observation from 25 years ago that numbers of neutrophils and levels of CXCL8/IL-8 in the peritoneal effluent, biomarkers that www.nature.com/scientificreports/. Our findings shows that miR-223 in particular is a promising biomarker that is produced by neutrophils, increased in acute peritonitis, and associated with extracellular vesicles in infected PD effluent
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