December 2022 - Rebecca Herzog

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Dr. Rebecca Herzog

MedUni Wien RESEARCHER OF THE MONTH December 2022

Life-saving renal replacement therapy by peritoneal dialysis (PD) is limited in use and duration by progressive impairment of peritoneal membrane integrity and homeostasis. Preservation of peritoneal membrane integrity during chronic PD remains an urgent but long unmet medical need. PD therapy failure results from peritoneal fibrosis and angiogenesis caused by PD fluid induced mesothelial damage. The study reports that addition of lithium chloride (LiCl) to PD fluid is a translatable intervention to counteract PD-induced membrane damage. LiCl improved mesothelial cell survival and a combined omics analysis identified alpha B-crystallin as mediator of membrane remodeling. LiCl also reduced fibrosis- and angiogenesis-associated processes. LiCl-supplemented PD fluid promoted morphological preservation of mesothelial cells and the submesothelial zone in a mouse model of chronic PD. Thus, repurposing LiCl as a cytoprotective PD fluid additive may offer a translatable therapeutic strategy to combat peritoneal membrane deterioration during PD therapy.

Selected Literature

1. Herzog R, Sacnun JM, González-Mateo G, Bartosova M, Bialas K, Wagner A, Unterwurzacher M, Sobieszek IJ, Daniel-Fischer L, Rusai K, Pascual-Antón L, Kaczirek K, Vychytil A, Schmitt CP, López-Cabrera M, Alper SL, Aufricht C, Kratochwill K. Sci Transl Med. 2021 doi: 10.1126/scitranslmed.aaz9705

2. Li, P. K., et al. Changes in the worldwide epidemiology of peritoneal dialysis, Nat Rev Nephrol, 2017, doi: 10.1038/nrneph.2016.181

3. Teitelbaum, I., Peritoneal Dialysis, N Engl J Med, 2021, doi: 10.1056/NEJMra2100152

4. Bartosova, M., Zhang, C., Schaefer, B., Herzog, R., et al. Glucose Derivative Induced Vasculopathy in Children on Chronic Peritoneal Dialysis, Circ Res., 2021,  doi: 10.1161/CIRCRESAHA.121.319310

5. Herzog, R., et al Dynamic O-linked N-acetylglucosamine modification of proteins affects stress responses and survival of mesothelial cells exposed to peritoneal dialysis fluids, J Am Soc Nephrol, 2014, doi: 10.1681/ASN.2013101128

6. Herzog, R., et al, Effects of Alanyl-Glutamine Treatment on the Peritoneal Dialysis Effluent Proteome Reveal Pathomechanism-Associated Molecular Signatures, Mol Cell Proteomics, 2018, doi: 10.1074/mcp.RA117.000186

7. Vychytil, A.*, Herzog, R.*, et al, A randomized controlled trial of alanyl-glutamine supplementation in peritoneal dialysis fluid to assess impact on biomarkers of peritoneal health, Kidney Int, 2018, doi: 10.1016/j.kint.2018.08.031