Name: a rat orthotopic renal transplantation model for renal allograft rejection
Uploaded: 2022-02-02T15:00:00
Description: Watch this Scientific Journal Video about A Rat Orthotopic Renal Transplantation Model for Renal Allograft Rejection at JoVE.com

This work was supported by the National Natural Science Foundation of China (81870304) to Jun Li and by the Else Kr&#246;ner-Fresenius-Stiftung (Nr. 2017_A28) to Marcus Groettrup.

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...

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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&#39...

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. Consequently, the preclinical studies that elucidate the mechanisms of immune and pathologic rejection of renal allografts contribute to finding novel targets and developing relevant effective pharmaceuticals to prevent the rejection of renal allografts and eventually prolong the survival of patients.
Many potential immunological and pathophysiological mechanisms of renal allograft rejection have been proposed recently in rat model studies of orthotopic renal transplantation4,5,6,7,8. These findings propose several novel targets and relevant interfering approaches as promising therapeutics to suppress renal allograft rejection, such as complement regulatory factors and anti-CD59 antibodies6, immunoproteasome, and epoxyketone inhibitors7,8. Thus, rat orthotopic renal transplantation is an ideal preclinical model to investigate the mechanisms of immune rejection and pathologic injury of renal allografts after kidney transplantation.
Rat kidney transplantation has gradually shifted from heterotopic implantation of donor&#39;s kidneys9 to orthotopic renal implantation using end-to-side anastomosis of vessels or using end-to-end anastomosis of the ureter using a cuff method10,11,12. The present study describes detailed protocols of the orthotopic renal transplantation between rats using end-to-end anastomosis to recipients&#39; renal artery and renal vein, and an end-to-side &#34;tunnel&#34; method of ureter-bladder anastomosis, which avoids the ischemia of the lower body and the thrombosis of inferior vena cava and reduces postoperative urine leakage and the twist of the ureter.

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a rat orthotopic renal transplantation model for renal allograft rejection

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.

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...

Watch this Scientific Journal Video about A Rat Orthotopic Renal Transplantation Model for Renal Allograft Rejection at JoVE.com

A Rat Orthotopic Renal Transplantation Model for Renal Allograft Rejection

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.

Renal allograft rejection limits the long-term survival of patients after renal transplantation. Rat orthotopic renal transplantation is an essential ...

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