Peritoneal dialysis

Pathophysiology of the peritoneum and peritoneal dialysis

This line of research has a long tradition in the Department of Pathophysiology and covers both basic problems of peritoneal cell biology those related to their role in peritoneal dialysis. These studies have been the subject of international cooperation many times and focus on:

  1. the role of peritoneal mesothelial cells in maintaining intraperitoneal homeostasis, and contributing to peritoneal inflammation, fibrosis, angiogenesis and transport,
  2. biocompatibility of dialysis fluids towards peritoneal cells,
  3. peritoneal mesothelial cell senescence and phenotypic transition of mesothelial cells into fibroblast-like cells during dialysis,
  4. identification of different subpopulations of fibroblasts residing in the peritoneal membrane.

Selected publications:

  1. Witowski J, Jörres A, Coles GA, Williams JD, Topley N. Superinduction of IL-6 synthesis in human peritoneal mesothelial cells is related to the induction and stabilization of IL-6 mRNA. Kidney Int 1996; 50: 1212-1223.
    doi: 10.1038/ki.1996.430
  2. Bręborowicz A, Rodela H, Karon J, Martis L, Oreopoulos DG: In vitro simulation of the effect of peritoneal dialysis solution on mesothelial cells. Am J Kidney Dis 1997; 29: 404-409.
    doi: 1016/s0272-6386(97)90202-x
  3. Połubinska A, Pawlaczyk K, Kuzlan-Pawlaczyk M, Wieczorowska-Tobis K, Chen C, Moberly JB, Martis L, Breborowicz A, Oreopoulos DG. Dialysis solution containing hyaluronan: Effect on peritoneal permeability and inflammation in rats .Kidney Int 2000; 57:1182-1189.
    doi: 10.1046/j.1523-1755.2000.00946.x
  4. Witowski J, Wiśniewska J, Korybalska K, Bender TO, Bręborowicz A, Gahl GM, Frei U, Passlick-Deetjen J, Jörres A. Prolonged exposure to glucose degradation products impairs viability and function of human peritoneal mesothelial cells. J Am Soc Nephrol 2001; 12: 2434-2441.
    doi: 1681/ASN.V12112434-3
  5. Witowski J, Korybalska K, Książek K, Wiśniewska-Elnur J, Jörres A, Lage C, Schaub T, Passlick-Deetjen J, Bręborowicz A, Grzegorzewska A, Książek A, Liberek T, Lichodziejewska-Niemierko M, Majdan M, Rutkowski B, Stompor T, Sulowicz W. Peritoneal dialysis with solutions low in glucose degradation products is associated with improved biocompatibility profile towards peritoneal mesothelial cells. Nephrol Dial Transplant 2004; 19: 917-924.
    doi: 10.1093/ndt/gfh013
  6. Bręborowicz A, Witowski J, Połubińska A, Pyda M, Oreopoulos D. L-2-Oxothiazolidine-4-carboxylic acid reduces in vitro cytotoxicity of glucose degradation products. Nephrol Dial Transplant 2004; 19: 3005-3011.
    doi: 10.1093/ndt/gfh539
  7. Książek K, Piwocka K, Brzezińska A, Sikora E, Zabel M, Bręborowicz A, Jörres A, Witowski J. Early loss of proliferative potential of human peritoneal mesothelial cells in culture: the role of p16INK4a-mediated premature senescence. J Appl Physiol 2006; 100: 988-995.
    doi: 10.1152/japplphysiol.01086.2005
  8. Witowski J, Książek K, Warnecke C, Kuźlan M, Korybalska K, Tayama H, Wiśniewska-Elnur J, Pawlaczyk K, Trómińska J, Bręborowicz A, Jörres A. Role of mesothelial cell-derived G-CSF in IL-17-induced neutrophil accumulation in the peritoneum. Kidney Int 2007; 71: 514-525.
    doi: 10.1038/sj.ki.5002082
  9. Książek K, Mikuła-Pietrasik J, Jörres A, Witowski J. Oxidative stress-mediated early senescence contributes to the short replicative lifespan of human peritoneal mesothelial cells. Free Radic Biol Med 2008; 45: 460-467.
    doi: 10.1016/j.freeradbiomed.2008.04.032
  10. Książek K, Mikuła-Pietrasik J, Olijslagers S, Jörres A, von Zglinicki T, Witowski J. Vulnerability to oxidative stress and different patterns of senescence in human peritoneal mesothelial cell strains. Am J Physiol 2009; 296: R374-R382.
    doi: 10.1152/ajpregu.90451.2008
  11. Witowski J, Tayama H, Książek K, Wanic-Kossowska M, Bender TO, Jörres A. Human peritoneal fibroblasts are a potent source of neutrophil-targeting cytokines: a key role of IL-1β Lab Invest 2009; 89: 414-424.
    doi: 10.1038/labinvest.2009.1
  12. Catar R, Witowski J, Wagner P, Schramm IA, Kawka E, Philippe A, Dragun D, Jörres A. The proto-oncogene c-Fos transcriptionally regulates VEGF production during peritoneal inflammation. Kidney Int 2013; 84: 1119-1128.
    doi: 10.1038/ki.2013.217
  13. Pawlaczyk K, Baum E, Schwermer K , Hoppe K , Lindholm B , Breborowicz A Animal Models of Peritoneal Dialysis: Thirty Years of Our Own Experience. Biomed Res Int 2015;2015:261813.
    doi: 10.1155/2015/261813
  14. Bartosova M, Rudolf A, Pichl S, Schmidt K, Okun JG, Straub B, Rutkowski R, Witowski J, Schmitt Increased storage and secretion of phosphatidylcholines by senescent human peritoneal mesothelial cells. Clin Exp Nephrol 2016; 20: 544-551.
    doi: 10.1007/s10157-015-1192-1
  15. Catar R, Witowski J, Zhu N, Lücht C, Soria A, Fernandez J, Chen L, Jones SA, Fielding CA, Rudolf A, Topley N, Dragun D, Jörres A. IL-6 trans-signaling links inflammation with angiogenesis in the peritoneal membrane. J Am Soc Nephrol 2017; 28: 1188-1199.
    doi: 10.1681/ASN.2015101169
  16. Lopez-Anton M, Rudolf A, Baird DM, Roger L, Robinson RE, Witowski J, Fraser DJ, Bowen T. Telomere length profiles in primary human peritoneal mesothelial cells are consistent with senescence. Mech Ageing Dev 2017; 164: 37-40.
    doi: 10.1016/j.mad.2017.03.010
  17. Kawka E, Witowski J, Bartosova M, Catar R, Rudolf A, Philippe A, Rutkowski R, Schaefer B, Schmitt CP, Dragun D, Jörres A. Thy-1+/- fibroblast subsets in the human peritoneum. Am J Physiol 2017; 313: F1116-F1123.
    doi: 10.1152/ajprenal.00274.2017
  18. Kawka E, Witowski J, Sandoval P, Rudolf A, Rynne Vidal A, Lopez-Cabrera M, Jörres A. Epithelial-to-mesenchymal transition and migration of human peritoneal mesothelial cells undergoing senescence. Perit Dial Int 2019; 39: 35-41.
    doi: 10.3747/pdi.2017.00244
  19. Witowski J, Sikorska D, Rudolf A, Miechowicz I, Kamhieh-Milz J, Jörres A, Bręborowicz A. Quality of design and reporting of animal research in peritoneal dialysis: A scoping review. Perit Dial Int 2020; 40: 394-404.
    doi: 10.1177/0896860819896148
  20. Catar RA, Chen L, Cuff SM, Kift-Morgan A, Eberl M, Kettritz R, Kamhieh-Milz J, Moll G, Li Q, Zhao H, Kawka E, Zickler D, Parekh G, Davis P, Fraser DJ, Dragun D, Eckardt K-U, Jörres A, Witowski J. Control of neutrophil influx during peritonitis by transcriptional cross-regulation of chemokine CXCL1 by IL-17 and IFN-γ. J Pathol 2020; 251: 175-180.
    doi:10.1002/path.5438
  21. Catar R, Bartosova M, Kawka E, Chen L, Marinovic I, Zhang C, Zhao H, Wu D, Zickler D, Stadnik H, Karczewski M, Kamhieh-Milz J, Jörres A, Moll G, Schmitt CP and Witowski J. Angiogenic role of mesothelium-derived chemokine CXCL1 during unfavorable peritoneal tissue remodeling in patients receiving peritoneal dialysis as renal replacement therapy. Front Immunol 13: 821681.
    doi: 10.3389/fimmu.2022.82168
  22. Trionfetti, F.; Marchant, V.; González-Mateo, G.T.; Kawka, E.; Márquez-Expósito, L.; Ortiz, A.; López-Cabrera, M.; Ruiz-Ortega, M.; Strippoli, R. Novel Aspects of the Immune Response Involved in the Peritoneal Damage in Chronic Kidney Disease Patients under Dialysis. Int. J. Mol. Sci. 2023, 24, 5763. https://doi.org/10.3390/ijms24065763