Addition of alanyl-glutamine to dialysis fluid restores peritoneal cellular stress responses ± a first-in-man trial

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Abstract

© 2016 Kratochwill et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Backgroun Peritonitis and ultrafiltration failure remain serious complications of chronic peritoneal dialysi (PD). Dysfunctional cellular stress responses aggravate peritoneal injury associate with PD fluid exposure, potentially due to peritoneal glutamine depletion. In this randomize cross-over phase I/II trial we investigated cytoprotective effects of alanyl-glutamin (AlaGln) addition to glucose-based PDF Method In a prospective randomized cross-over design, 20 stable PD outpatients underwent paire peritoneal equilibration tests 4 weeks apart, using conventional acidic, single chambe 3.86% glucose PD fluid, with and without 8 mM supplemental AlaGln. Heat-shock protei 72 expression was assessed in peritoneal effluent cells as surrogate parameter of cellula stress responses, complemented by metabolomics and functional immunocompetenc assays Result AlaGln restored peritoneal glutamine levels and increased the primary outcome heat-shoc protein expression (effect 1.51-fold, CI 1.07±2.14; p = 0.022), without changes in peritonea ultrafiltration, small solute transport, or biomarkers reflecting cell mass and inflammation Further effects were glutamine-like metabolomic changes and increased ex-vivo LPS-stimulate cytokine release from healthy donor peripheral blood monocytes. In patients with history of peritonitis (5 of 20), AlaGln supplementation decreased dialysate interleukin-levels. Supplemented PD fluid also attenuated inflammation and enhanced stimulated cytokin release in a mouse model of PD-Associated peritonitis Conclusio We conclude that AlaGln-supplemented, glucose-based PD fluid can restore peritoneal cellula stress responses with attenuation of sterile inflammation, and may improve peritonea host-defense in the setting of PD.

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Kratochwill, K., Boehm, M., Herzog, R., Gruber, K., Lichtenauer, A. M., Kuster, L., … Vychytil, A. (2016). Addition of alanyl-glutamine to dialysis fluid restores peritoneal cellular stress responses ± a first-in-man trial. PLoS ONE, 11(10). https://doi.org/10.1371/journal.pone.0165045

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