Abstract: FR-PO1001

Organ-Specific Immunosuppression in Kidney Transplantation

Session Information

Category: Transplantation

  • 1701 Transplantation: Basic and Experimental

Authors

  • Kentrup, Dominik Richard, University Hospital Münster, Münster, Germany
  • Schütte-Nütgen, Katharina, University Hospital Münster, Münster, Germany
  • Pawlski, Helga, University Hospital Münster, Münster, Germany
  • Pavenstädt, Hermann, University Hospital Münster, Münster, Germany
  • Hermann, Sven, European Institute for Molecular Imaging - EIMI, Muenster, Germany
  • Schaefers, Michael, European Institute for Molecular Imaging - EIMI, Muenster, Germany
  • Larbig, Gregor, Merck KGaA,, Darmstadt, Germany
  • Kuebelbeck, Armin, Merck KGaA,, Darmstadt, Germany
  • Reuter, Stefan, University Hospital Münster, Münster, Germany
Background

Severe side effects attributable to immunosuppressive therapy are a major obstacle in organ transplantation. In this study we assessed a kidney-specific drug delivery mechanism and show that prednisolone, coupled to a specific polypeptide is selectively taken up by the kidney in rats which underwent renal transplantation, avoiding adverse systemic effects.

Methods

All experiments were performed using male rats, ten groups of animals were assessed (N=5-6): Syngeneically (Lewis Brown Norway F1 to Lewis Brown Norway F1) and allogeneically (Lewis Brown Norway F1 to Lewis) transplanted rats without immunosuppression, as well as
allogeneically transplanted rats receiving either normal or modified prednisolone at two different concentrations (4mg/kg/12h or 16mg/kg/12h, i.p).
Immunosuppressive treatment was either preventive (continuous treatment until the end of the experiment 4 days post surgery; six groups) or therapeutic (started 4 days after surgery and maintained for 3 days until day 7 post surgery; 4 groups, no low dose treatment).
Treatment efficiency was evaluated by 18F-FDG positron emission tomography in the preventive experimental setting 4 days post surgery, as well as on day 4 (baseline), day 5 and day 7 post surgery in the therapeutic setting. Moreover, histological analyses were performed and blood glucose levels were measured to assess systemic effects.

Results

High dosage treatment with normal prednisolone significantly reduced renal 18F-FDG accumulation and histological signs of rejection both in the preventive and the therapeutic setting, low dose treatment had no effect. In comparison, animals treated with modified prednisolone showed significantly reduced signs of renal graft rejection even under low dose treatment in the preventive setting, high dose treatment was at least as effective as conventional treatment in both the preventive and therapeutic setting.
Moreover, treatment with modified prednisolone did not result in elevated blood glucose levels, contrary to normal prednisolone.

Conclusion

Immunosuppressive treatment with the modified, kidney specific prednisolone proved to be as least as effective as normal prednisolone and may even outperform the latter. In the case of renal transplantations, organ-specific immunosuppression is possible.