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Bladder-Drained Pancreas Transplantation: Urothelial Innate Defenses and UTI Susceptibility

Lookup NU author(s): Matt Byrne, Dr Catherine Mowbray, Dr Phillip Aldridge, Lauren Drage, Ased Ali, Lucy Bates, Dr Judith Hall, Colin Wilson

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Abstract

© 2018 Background: Pancreas transplantation restores insulin secretion in type 1 diabetes mellitus. The graft also produces exocrine secretions that can be drained enterically (enteric drainage [ED]) or via the bladder (bladder drainage [BD]). We suggest that in BD transplants, such secretions destroy bladder innate immunity, specifically host defense peptides/proteins (HDPs), which increases patient susceptibility to recurrent urinary tract infections (rUTIs). Materials and methods: BD and ED patient records were reviewed retrospectively for UTIs. Urine samples from ED and BD transplant recipients were analyzed for pH, the HDPs β-defensin 2 (HBD2) and lipocalin-2, and amylase concentrations. In vitro, bacterial growth curves and antimicrobial assays were used to evaluate the effects of pH, HBD2, and HBD2 + pancreatic digestive enzymes (pancreatin) on uropathogenic Escherichia coli (UPEC) survival and growth. Results: Urinalysis revealed a significant difference in pH between the BD and ED cohorts (7.2 ± 0.8 versus 6.7 ± 0.8; P = 0.012). Urinary HDPs were measured and BD, but not ED, lipocalin-2 concentrations were significantly decreased compared with those of diabetics awaiting transplant (P < 0.05). In vitro, an alkaline environment, pH 8.0, concomitant with the urine of the patient who underwent BD transplantation, significantly reduced UPEC growth (P < 0.05); addition of pancreatin to the growth medium was associated with a significant increase (P < 0.001) in growth rate. Antimicrobial data suggested significant UPEC killing in the presence of HBD2 (P < 0.01), but not in the presence of HBD2 + pancreatin (>12,500 amylase units). Conclusions: These in vivo and in vitro data suggest that BD pancreatic exocrine secretions inactivate the bladder innate defenses, which facilitate UPEC growth and underpins the increased susceptibility of patients who underwent BD pancreas transplantation to rUTIs.


Publication metadata

Author(s): Byrne M, Singh A, Mowbray CA, Aldridge PD, Drage LKL, Ali ASM, Bates L, Hall J, Wilson C

Publication type: Article

Publication status: Published

Journal: Journal of Surgical Research

Year: 2019

Volume: 235

Pages: 288-297

Print publication date: 01/03/2019

Online publication date: 02/11/2018

Acceptance date: 11/09/2018

ISSN (print): 0022-4804

ISSN (electronic): 1095-8673

Publisher: Academic Press Inc.

URL: https://doi.org/10.1016/j.jss.2018.09.028

DOI: 10.1016/j.jss.2018.09.028


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