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In This Article

  • Summary
  • Abstract
  • Introduction
  • Protocol
  • Representative Results
  • Discussion
  • Acknowledgements
  • Materials
  • References
  • Reprints and Permissions

Summary

The rat orthotopic renal transplantation model contributes to investigating the mechanism of renal allograft rejection. The current model increases the recipients' survival without interference with blood supply and venous reflux of the lower body using an end-to-end anastomosis of kidney implantation and an end-to-side "tunnel" method of ureter-bladder anastomosis.

Abstract

Renal allograft rejection limits the long-term survival of patients after renal transplantation. Rat orthotopic renal transplantation is an essential model to investigate the mechanism of renal allograft rejection in pre-clinical studies and could aid in the development of novel approaches to improve the long-term survival of renal allografts. Donor kidney implantation in rat orthotopic renal transplantation is commonly performed by end-to-side anastomosis to recipients' aorta and inferior vena cava. In this model, the donor's kidney was implanted using end-to-end anastomosis to the recipients' renal artery and renal vein. The donor's ureter was anastomosed to the recipient's bladder in an end-to-side 'tunnel' method. This model contributes to better healing of ureter-bladder anastomosis and increases the recipients' survival by avoiding interference with blood supply and venous reflux of the lower body. This model can be used to investigate the mechanisms of acute and chronic immune and pathologic rejection of renal allografts. Here, the study describes the detailed protocols of this orthotopic renal transplantation between rats.

Introduction

Renal transplantation has become the most effective therapeutic approach for patients with end-stage renal function failure. However, T cell-mediated acute rejection and alloantibody-mediated humoral immune rejection result in the pathologic injury of renal allografts and limit the short-term and long-term survival of patients after kidney transplantation1,2,3. Unfortunately, the effective pharmaceuticals that prevent the rejection of renal allografts are still lacking, because the exact mechanisms of immune and pathologic rejection of renal allografts are not clear. Conseque....

Protocol

Inbred 8-10 weeks old male F344 and Lewis rats (200 g to 250 g) were commercially obtained. Allogeneic left kidney transplantation was performed between male F344 and Lewis rats. F344 rats were used as donors and syngeneic recipients, and Lewis rats served as allogeneic recipients. All animal handling procedures were conducted in compliance with guidelines for the Care and Use of Laboratory Animals published by NIH, and all animal experimental protocols were approved by the Animal Care and Use Committee of Chongqing Univ.......

Representative Results

In this rat orthotopic renal transplantation model, the recipient rats move normally after operation. To observe the chronic rejection of renal allograft, recipient rats are raised for 10 weeks after transplantation, and the total survival rate of recipient rats at this time point is approximately 90%. The major causes of death are bleeding and leakage of urine post-operation. The other major complications include bleeding during the operation, thrombosis in renal vessels, and hydronephrosis, whose respective incidence i.......

Discussion

Renal transplantation in the rat is a challenging work requiring a high level of micro-surgery techniques and the operation techniques have been optimized several times. From the beginning, Gonzalez et al. implanted the donor kidney into the neck of the recipient and anastomosed the donor ureter to the skin9. However, because of the high incidence of urinary infection and stenosis of the donor ureter, the operation was abandoned in a short time. Subsequently, the implant operation of the donor'.......

Acknowledgements

This work was supported by the National Natural Science Foundation of China (81870304) to Jun Li and by the Else Kröner-Fresenius-Stiftung (Nr. 2017_A28) to Marcus Groettrup.

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Materials

NameCompanyCatalog NumberComments
 10-0 Polyamide Monofilament sutureB.Braun Medical Inc.G0090781
 4-0 Polyamide Monofilament sutureB.Braun Medical Inc.C1048451
 8-0 Polyamide Monofilament sutureB.Braun Medical Inc.C2090880
BuprenorphineUS Biological life Sciences352004
ElectrocoagulatorElectrocoagulatorZJ1099
F344 and Lewis ratsCenter of Experimental Animals (Tongji Medical College, Huazhong University of Science and Technology, China)NA
GauzeHenan piaoan group Co., LTD10210402
Heating padGuangzhou Dewei Biological Technology Co., LTDDK0032
HeparinNorth China Pharmaceutical Co., LTD2101131-2
Injection syringe (1 ml and 10 ml)Shandong weigao group medical polymer Co., LTD20211001
IsofluraneRWD Life Science Co., LTD21070201
Penicillin G SodiumWuhan HongDe Yuexin pharmatech co.,Ltd69-57-8
Scalp needle (24 G)Hongyu Medical Group20183150210
ShaverBeyotimeFS600
Small animal anesthesia machineRWD Life ScienceR500
Small Animal Surgery KitBeyotimeFS500
Sodium chloride injectionSouthwest pharmaceutical Co., LTDH50021610
Surgical operation microscopeTiannuoxiang Scientific Instrument Co. , Ltd, Beijing, ChinaSZX-6745
SwabYubei Medical Materials Co., LTD21080274
TapeMinnesota Mining Manufacturing Medical Equipment (Shanghai) Co., LTD1911N68
UW solutionBristol-Myers Squibb Company17HB0002

References

  1. Cooper, J. E., Wiseman, A. C. Novel immunosuppressive agents in kidney transplantation. Clinical Nephrology. 73 (5), 333-343 (2010).
  2. Colaneri, J. An overview of transplant immunosupp....

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