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Mol Cell Proteomics. 2018 Mar;17(3):516-532. doi: 10.1074/mcp.RA117.000186. Epub 2017 Dec 4.

Effects of Alanyl-Glutamine Treatment on the Peritoneal Dialysis Effluent Proteome Reveal Pathomechanism-Associated Molecular Signatures.

Author information

1
From the ‡Division of Pediatric Nephrology and Gastroenterology, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria.
2
§Christian Doppler Laboratory for Molecular Stress Research in Peritoneal Dialysis, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria.
3
¶CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
4
‖Division of Nephrology, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
5
**Department of Medicine, Harvard Medical School, Boston, Massachusetts.
6
‡‡Department of Medicine III, Division of Nephrology and Dialysis, Medical University of Vienna, Vienna, Austria.
7
From the ‡Division of Pediatric Nephrology and Gastroenterology, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria; klaus.kratochwill@meduniwien.ac.at.

Abstract

Peritoneal dialysis (PD) is a modality of renal replacement therapy in which the high volumes of available PD effluent (PDE) represents a rich source of biomarkers for monitoring disease and therapy. Although this information could help guide the management of PD patients, little is known about the potential of PDE to define pathomechanism-associated molecular signatures in PD.We therefore subjected PDE to a high-performance multiplex proteomic analysis after depletion of highly-abundant plasma proteins and enrichment of low-abundance proteins. A combination of label-free and isobaric labeling strategies was applied to PDE samples from PD patients (n = 20) treated in an open-label, randomized, two-period, cross-over clinical trial with standard PD fluid or with a novel PD fluid supplemented with alanyl-glutamine (AlaGln).With this workflow we identified 2506 unique proteins in the PDE proteome, greatly increasing coverage beyond the 171 previously-reported proteins. The proteins identified range from high abundance plasma proteins to low abundance cellular proteins, and are linked to larger numbers of biological processes and pathways, some of which are novel for PDE. Interestingly, proteins linked to membrane remodeling and fibrosis are overrepresented in PDE compared with plasma, whereas the proteins underrepresented in PDE suggest decreases in host defense, immune-competence and response to stress. Treatment with AlaGln-supplemented PD fluid is associated with reduced activity of membrane injury-associated mechanisms and with restoration of biological processes involved in stress responses and host defense.Our study represents the first application of the PDE proteome in a randomized controlled prospective clinical trial of PD. This novel proteomic workflow allowed detection of low abundance biomarkers to define pathomechanism-associated molecular signatures in PD and their alterations by a novel therapeutic intervention.

PMID:
29208752
PMCID:
PMC5836375
DOI:
10.1074/mcp.RA117.000186
[Indexed for MEDLINE]
Free PMC Article

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