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Kidney Week

Abstract: SA-PO695

Ribonucleases Defend the Peritoneum from Invading Pathogens During Chronic Peritoneal Dialysis

Session Information

  • Peritoneal Dialysis - II
    November 04, 2017 | Location: Hall H, Morial Convention Center
    Abstract Time: 10:00 AM - 10:00 AM

Category: Dialysis

  • 608 Peritoneal Dialysis

Authors

  • Dhingra, Neha, Nationwide Children''s Hospital, Columbus, Ohio, United States
  • Cortado, Hanna H., Nationwide Children''s Hospital, Columbus, Ohio, United States
  • Gupta, Sudipti, Nationwide Childrens Hospital, Columbus, Ohio, United States
  • Li, Birong, Nationwide Children''s Hospital, Columbus, Ohio, United States
  • Jackson, Ashley R., Nationwide Children''s Hospital, Columbus, Ohio, United States
  • Cohen, Ariel, Nationwide Children''s Hospital, Columbus, Ohio, United States
  • Ching, Christina B., Nationwide Childrens Hospital, Columbus, Ohio, United States
  • Spencer, John David, Nationwide Children''s Hospital, Columbus, Ohio, United States
  • Ayoob, Rose M., Nationwide Children''s Hospital, Columbus, Ohio, United States
  • Becknell, Brian, Nationwide Children''s Hospital, Columbus, Ohio, United States
Background

Peritonitis is a rare but serious complication in ESRD patients undergoing chronic peritoneal dialysis (PD). Improvements in standardized technique have reduced but not eliminated the incidence of peritonitis, which remains the leading cause of PD failure and change in dialysis modality. The RNase A superfamily encodes cationic antimicrobial peptides (AMPs) with broad spectrum activity against pathogens implicated in peritonitis in the PD population. Here, we evaluated the expression of these AMPs in the baseline PD effluents of pediatric ESRD patients undergoing chronic PD, in the absence of peritonitis.

Methods

PD effluent was collected from seven pediatric patients undergoing chronic cycling PD, prior to starting nightly dialysis. We also collected ascites fluid from patients with acute kidney injury undergoing paracentesis or acute PD. RNases were analyzed by immunocytochemistry, qRT-PCR Western blotting, and ELISA. RNase localization within omentum was analyzed by immunofluorescence microscopy. RNase bactericidal activity was evaluated by incubation with Staphylococcus epidermidis, followed by plating and colony enumeration.

Results

Viable cells recovered from PD effluent express RNase3, RNase6, and RNase7 mRNA and protein. These AMPs are present in cell-free supernatants from ascites and PD effluent, and RNase7 levels are the most abundant. Immunocytochemistry identifies RNase3+ eosinophils, RNase6+ macrophages, and RNase7+ mesothelial cells as sources of these AMPs. These RNases are distributed similarly in omentum, and RNase7 expression is detected in immortalized mesothelial cells. Functionally, recombinant peptides derived from RNase 3, 6, and 7 exhibit potent bactericidal activity toward S. epidermidis.

Conclusion

Multiple AMPs in the RNase A superfamily are present in peritoneal fluid of patients with ESRD undergoing PD. These AMPs have distinct cellular sources and exhibit antimicrobial activity toward S. epidermidis. The omentum is a source of multiple AMP producing cells, a finding with potential clinical implications given the practice of omentectomy at PD catheter insertion. Strategies aimed at preserving or enhancing RNase levels and antimicrobial activity may comprise a formidable approach to peritonitis prevention and treatment.