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Kidney Week

Abstract: TH-PO764

The Direct Effect of Mycophenolate Mofetil on Podocytes in Nephrotoxic Serum Nephritis

Session Information

Category: Glomerular Diseases

  • 1403 Podocyte Biology

Authors

  • Hackl, Agnes, Department of Pediatrics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
  • Nüsken, Eva, Department of Pediatrics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
  • Abo Zed, Seif El Din, Department of Pediatrics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
  • Wiesner, Eva, CECAD, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
  • Dafinger, Claudia, CECAD, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
  • Bohl, Katrin, CECAD, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
  • Hackl, Matthias, CECAD, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
  • Nüsken, Kai Dietrich, Department of Pediatrics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
  • Weber, Lutz Thorsten, Department of Pediatrics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
Background

Mycophenolate mofetil (MMF) is applied in proteinuric kidney diseases, but the exact mechanism of its effect on podocytes is still unknown. Our previous in vitro experiments suggested that MMF can ameliorate podocyte damage via restoration of the Ca2+-actin cytoskeleton axis. The goal of this study was to characterize podocyte biology during MMF treatment in proteinuric glomerulopathy.

Methods

Nephrotoxic serum (NTS) nephritis (NTN) was induced in three-week old wild-type mice. On day 3, half of the mice were treated with MMF (100 mg/kgBW/d p.o.) for one week. On day 10, we performed proteomic analysis of glomeruli as well as super-resolution imaging of the slit diaphragm. For multiphoton imaging of Ca2+concentration ([Ca2+]i), the experimental design was repeated in mice expressing podocyte-specific Ca2+ sensor.

Results

MMF ameliorated the proteinuria induced by NTS. We identified significant changes in the abundance of proteins involved in Ca2+ signaling and actin cytoskeleton regulation, which was further confirmed by direct [Ca2+]i imaging in podocytes showing decreased Ca2+levels after MMF treatment. This was associated with a tendency to restoration of podocyte foot process structure.

Conclusion

Here, we provide evidence that MMF has a substantial direct effect on podocytes. MMF contributes to improvement of [Ca2+]i and amelioration of the disorganized actin cytoskeleton in podocytes. These data extend the knowledge of direct effects of immunosuppressants on podocytes that may contribute to a more effective treatment of proteinuric glomerulopathies with the least possible side effects.