Injury-induced inflammation and inadequate HSP expression in mesothelial cells upon repeat exposure to dual-chamber bag peritoneal dialysis fluids.
OBJECTIVE
Peritoneal dialysis fluids (PDFs) may induce inadequate heat-shock protein (HSP) expression and injury-related inflammation in exposed mesothelial cells. The aim of this study was to relate cellular injury to these cellular responses in mesothelial cells following repeated exposure to 3 commercial PDFs with different biocompatibility profiles.


METHODS
Primary cultures of human peritoneal mesothelial cells (HPMC) were exposed to a 1:2 mixture of cell culture medium and CAPD2 (single-chamber bag PDF; Fresenius, Bad Homburg, Germany), Physioneal (dual-chamber bag PDF; Baxter, Deerfield, IL, USA) or Balance (dual-chamber bag PDF, Fresenius) for up to 10 days exposure time (4 dwells). Supernatant was analyzed for LDH, IL-6, and IL-8, cells for HSP-72 expression, and protein content.


RESULTS
PDF exposure resulted in a biphasic pattern of cell damage switching from an earlier phase with increased injury by single-chamber PDF to a delayed phase with increased susceptibility to dual-chamber PDF. Sterile inflammation was related to LDH release over time and could be reproduced by exposure to necrotic cellular material. PDF exposure resulted in low HSP-72 expression in all tested PDFs.


CONCLUSIONS
Exposure to single-chamber as well as to dual-chamber bag PDFs induce increased vulnerability of mesothelial cells to repeated exposure of the same solution. These effects were delayed with dual-chamber PDFs. Injury-induced inflammation and impaired HSP expression upon PDF exposure might initiate a vicious cycle with progredient mesothelial cell damage upon repeated PDF exposure. Certainly, interventional studies and translation of these results into the in vivo system is needed.
Department of Nephrology and Medical Intensive Care, Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin - Germany.
Thorsten O
TO
Bender
Department of Pediatrics, Medical University, Vienna - Austria.
Klaus
K
Kratochwill
Department of Pediatrics, Medical University, Vienna - Austria.
Rebecca
R
Herzog
Department of Pediatrics, Medical University, Vienna - Austria.
Andrea
A
Ulbrich
Department of Pediatrics, Medical University, Vienna - Austria.
Michael
M
Böhm
Department of Nephrology and Medical Intensive Care, Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin - Germany.
Achim
A
Jörres
Department of Pediatrics, Medical University, Vienna - Austria.
Christoph
C
Aufricht
D015314:Dialysis Solutions / Q000494:pharmacology*; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D050884:HSP72 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D009852:Omentum / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010530:Peritoneal Dialysis
D015314:Dialysis Solutions; D050884:HSP72 Heat-Shock Proteins; D015850:Interleukin-6; D016209:Interleukin-8