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Volume: 19 Issue: 6 June 2021

FULL TEXT

CASE REPORT
Technical and Immunological Challenges in Early Kidney Regrafting

Abstract

Few reports concerning early organ regrafting are available in the literature, and those dedicated to kidney regrafting do not focus on allocation policies or retrieval surgical strategies. This report describes an unsuccessful living donor kidney transplant, where a 12-year-old female recipient who had received a kidney from her mother died on postoperative day 2 due to cerebral ischemia and became a brain-dead donor. The family agreed to a multiorgan donation since the previously transplanted kidney was highly performing. The organ had initially been allocated according to the blood group of the recipient (AB), although the donor’s (her mother) blood group was B; however, human leukocyte antigen matching was performed considering the donor’s human leukocyte antigen typing. The new recipient of the kidney was a 53-year-old man. Organ procurement was performed with adjunctive cannulation of the iliac vessels, to flush the transplanted kidney with preservation solution; the graft was then procured, including the previous vascular anastomoses. Implantation of the graft was performed on the iliac vessels of the recipient, which were anastomosed to the iliac vessels of the donor, leaving the previous vascular anastomoses untouched. Two years after the transplant, the patient is alive with a functioning graft. Early kidney regrafting is a safeand feasible procedure, on both the surgical and immunological sides. Although kidney recipients who experience brain death in the early postoperative period are few, they should be considered as viable organ donors. Also, allocating and retrieving such organs require few precautions compared with standard allocation and retrieval processes.


Key words : Multiorgan donation, Renal transplant

Case Report

Case description
A 12-year-old girl with Bardet-Biedl syndrome (obesity, psychomotor retardation, pigmentosa retinitis, polydactyly, renal impairment) was admitted to our hospital to receive a kidney transplant from a living donor (her mother). She had already undergone a previous kidney transplant 11 years before, with preservation of native kidneys. Subsequently, she developed chronic nephropathy due to arterial stenosis of the transplanted kidney, which was unsuccessfully treated with angioplasty.

On the scheduled day, she underwent a living donor kidney transplant from her 43-year-old mother. The blood group of the recipient was AB positive, with the following HLA antigen typing: HLA-A 01,24; HLA-B 51,52; and HLA-DRB 13,15. The blood group of the donor was B positive, with the following HLA antigen typing: HLA-A 24,32; HLA-B 35,51; and HLA-DR 11,13. A crossmatch was repeated 3 times and always resulted as negative.

The left kidney was retrieved from the donor with a retroperitoneal approach and was preserved in hypothermic solution (Celsior®, Institut Georges Lopez). Vascular anastomoses were performed in a standard fashion: terminolaterally on the external iliac vein and artery. The graft reperfusion occurred after 110 minutes of cold ischemia, and intraoperative diuresis was observed. A ureterovesical anastomosis was performed according to the Lich-Gregoir technique using a double J stent.

The immunosuppressive regimen consisted of 20 mg of basiliximab after reperfusion, 4 mg of tacrolimus every 12 hours, and 500 mg of steroids. The postoperative course was characterized by a prompt recovery of renal function in terms of good diuresis and serum creatinine and urea levels of 2.2 mg/dL and 130 mg/dL, respectively.

On postoperative day 2, the recipient suddenly went into a deep coma; she was reintubated and a cerebral computed tomography scan was performed showing an ischemic area in the right cerebellar hemisphere. Angiography was then performed, which demonstrated no intracerebral vascular flow. After the assessment of brain death according to the national legislation1 and with family consent to donation, she underwent organ procurement.

Among the neurological complications following organ transplant, cerebral hemorrhage may develop, and the transplanted recipient may become a brain-dead donor2-6; however, usually only organs other than the transplanted ones are considered for a new transplant. In the present case, the transplanted kidney was properly functioning, and we considered it correct to evaluate it for transplant. Moreover, the parents of the girl were kindly encouraging us to continue with a further donation of the previously donated kidney, with the intent to obtain a successful transplant from a living donation.

Our concerns about this type of procedure were mainly focused on the surgical technical and immunological aspects. No solid and reliable reports from the scientific literature were available to guide our decision-making process. The problems that we encountered and our proposed solutions are discussed below. Eventually, the kidney was transplanted in a 53-year-old man after 13 hours of cold ischemia. A standard immunosuppressive regimen was used: induction with thymoglobulin and steroids and maintenance therapy with tacrolimus and mycop­henolic acid. His renal function recovered progressively without necessity of hemodialysis, and he was discharged in good condition after 17 days without any severe surgical complication. Two years after the transplant, the patient was alive with a functioning graft.

Surgical issues
The first surgical problem that we encountered concerned the procurement of the transplanted kidney together with other organs (heart and liver). Usually, to perfuse all the abdominal organs (liver, kidney, pancreas, and small bowel) with hypothermic solution, an arterial cannula is placed inside the abdominal aorta at the origin of the inferior mesenteric artery, which is ligated to reduce the dispersion of the solution. In the present case, we needed to perfuse the transplanted kidney, which was anastomosed on the left external iliac vessels. Furthermore, the caliber of the iliac arteries was too small for cannulation and could not ensure an adequate perfusion to the liver and the transplanted kidney. Therefore, we decided to cannulate the aortic arch to perfuse the celiac axis, superior mesenteric artery, and left iliac artery.

We proceeded with a standard technique of liver procurement,7 and the transplanted kidney was procured together with the iliac vessels of the recipient, where the anastomoses were performed (Figure 1A). The ureter was disconnected at the level of the vesical anastomoses, and, during the bench surgery, the iliac vessels of the recipient and the left artery and vein of the living kidney were prepared for transplantation, leaving the previous vascular anastomoses untouched. Our concerns were focused on the length of the graft vessels; therefore, we decided to preserve the previous vascular anastomoses.

The vein anastomosis of the second kidney transplant was performed between the right external iliac vein of the second recipient and a vein patch of the external iliac vein of the first recipient, maintaining the vein anastomosis of the living-donor graft (Figure 1B). Thereafter, we checked for the best position for the arterial anastomoses to avoid any kinking of the vessels; we then closed the distal part of the external iliac artery of the first recipient with a running suture of polypropylene 6-0, close to the previous anastomoses with the artery of the living donor graft. We finally performed an arterial anastomosis between the right external iliac artery of the second recipient and the proximal part of the iliac artery of the first recipient (Figure 1C).

In conclusion, we used the first recipient’s iliac vessels as interposed vascular grafts to perform the second transplant with the living donor graft; in this way, the vascular anastomoses were performed in a standard fashion: terminolaterally on the external iliac vein and artery of the second recipient. At the end of the procedure, we checked the anastomoses and reperfused the graft after 40 minutes of warm ischemia time. The ureter of the graft showed adequate bleeding, suggesting good perfusion, so we performed a standard ureterovesical anastomosis according to the Lich-Gregoir technique using a double J stent.

Immunological issues
Usually in our transplant center, according to the local transplant organization (InterRegional Transplant Association), kidneys from deceased donors are allocated according to the following criteria: blood group identity, age (delta age inferior to 15 years), better HLA antigen match (at least 1 match in HLA class I and 1 match in HLA class II), and a negative T-cell crossmatch.8 The immunological issues that we faced concerned allocation criteria for this organ and the possible increased immune response it could trigger in the second recipient.

First, we decided to retransplant the kidney in an adult patient, instead of a pediatric one, because of the adult age of the living donor. We then decided to select the potential recipient among patients with AB blood group, as was the deceased donor, to minimize the risk of rejection from preformed antibodies. Next, we decided to consider the mother’s HLA typing instead of the first recipient’s typing to optimize the tolerance toward the graft.

According to the above-described decisions, the kidney from the girl was allocated to a 53-year-old man with polycystic kidney diseases undergoing hemodialysis. His blood group was AB positive, and the HLA typing was the following: HLA-A 1,24; HLA-B 63,39; and HLA-DR 11,13. A negative T-cell crossmatch was verified.

No rejection episodes were observed, and the “reused” graft had a prompt recovery with
serum creatinine level of 1.3 mg/dL at discharge and at the last follow-up (6 months after transplant). The immunosuppression regimen consisted of thymog­lobulin 1 mg/kg (75 mg) in 3 administrations (posttransplant days 0, 3, and 5), steroids (methylprednisolone 500 mg at day 0, 125 mg at days 1 and 2, 80 mg at days 3 and 4, 60 mg at days 5 and 6, 40 mg at days 7 and 8, and oral prednisone 20 mg/day tapered to 5 mg/day at day 30), tacrolimus 0.2 mg/kg/day to achieve blood levels of 10 to 15 ng/mL in the first month and then 5 to 8 ng/mL, and mycophenolic acid 1440 mg/day up to day 14 and then 720 mg/day.

A few conditions may have promoted the good graft recovery in the second recipient. First, the benign nephropathy of the 2 recipients may have allowed a better tolerance to the new graft in both cases. Second, although the graft experienced a double ischemia and reperfusion trauma, the addition of the 2 events may not have been detrimental because the procedure of living donation for the first transplant ensured a minimal cold ischemia time to the graft. Finally, the immunosuppressive drugs administered to the first recipient before brain death may have blunted the ischemia and reperfusion injury on the kidney.9

Discussion

As of this writing, renal transplant has the longest wait lists among solid-organ transplants, and many strategies have been proposed to reduce wait list time and optimize donor procurement, such as the utilization of extended criteria donors or donors after cardiac death.10 Regrafting of previously transplanted organ donors can contribute, even if marginally, to extend the donor pool and increase the number of available organs.


References:

  1. Geraci PM, Sepe V. Non-heart-beating organ donation in Italy. Minerva Anestesiol. 2011;77(6):613-623.
    CrossRef - PubMed
  2. Oliveras A, Roquer J, Puig JM, et al. Stroke in renal transplant recipients: epidemiology, predictive risk factors and outcome. Clin Transplant. 2003;17(1):1-8. doi:10.1034/j.1399-0012.2003.02042.x
    CrossRef - PubMed
  3. Nemec P, Bedanova H, Ostrizek T. Successful re-use of the transplanted heart. Ann Thorac Surg. 2010;90(4):1337-1338. doi:10.1016/j.athoracsur.2010.03.025
    CrossRef - PubMed
  4. Arvieux C, Cornforth B, Gunson B, et al. Use of grafts procured from organ transplant recipients. Transplantation. 1999;67(7):1074-1077. doi:10.1097/00007890-199904150-00025
    CrossRef - PubMed
  5. Tantawi B, Cherqui D, Duvoux C, Dhumeaux D, Fagniez PL. Reuse of a liver graft five days after initial transplantation. Transplantation. 1996;62(6):868-869. doi:10.1097/00007890-199609270-00029
    CrossRef - PubMed
  6. Castellote J, Llado L, Xiol X, et al. Successful reuse of liver grafts after death of the first recipient. Clin Transplant. 2006;20(5):604-608. doi:10.1111/j.1399-0012.2006.00524.x
    CrossRef - PubMed
  7. Ravaioli M, Grazi GL, Cescon M, et al. Liver transplantations with donors aged 60 years and above: the low liver damage strategy. Transpl Int. 2009;22(4):423-433. doi:10.1111/j.1432-2277.2008.00812.x
    CrossRef - PubMed
  8. Ferrari P, Lim W, Dent H, McDonald SP. Effect of donor-recipient age difference on graft function and survival in live-donor kidney transplantation. Nephrol Dial Transplant. 2011;26(2):702-708. doi:10.1093/ndt/gfq383
    CrossRef - PubMed
  9. Cicora F, Roberti J, Vasquez D, et al. Preconditioning donor with a combination of tacrolimus and rapamacyn to decrease ischaemia-reperfusion injury in a rat syngenic kidney transplantation model. Clin Exp Immunol. 2012;167(1):169-177. doi:10.1111/j.1365-2249.2011.04487.x
    CrossRef - PubMed
  10. Ravaioli M, De Pace V, Comai G, et al. Preliminary experience of sequential use of normothermic and hypothermic oxygenated perfusion for donation after circulatory death kidney with warm ischemia time over the conventional criteria - a retrospective and observational study. Transpl Int. 2018;31(11):1233-1244. doi:10.1111/tri.13311
    CrossRef - PubMed


Volume : 19
Issue : 6
Pages : 613 - 616
DOI : 10.6002/ect.2018.0326


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From the 1Division of General Surgery and Transplantation, and the 2Division of Nephrology, Dialysis and Transplantation, IRCCS Azienda Ospedaliero-Universitaria di Bologna, University of Bologna, Bologna, Italy
Acknowledgements: The authors contributed equally to the manuscript. The authors have not received any funding or grants in support of the presented research or for the preparation of this work and have no declarations of potential conflicts of interest.
Corresponding author: Matteo Ravaioli, Division of General Surgery and Transplantation, IRCCS Azienda Ospedaliero-Universitaria di Bologna, University of Bologna, Via Massarenti 9, 40138 Bologna, Italy
Phone: +39 051 2144810
E-mail: matteo.ravaioli@aosp.bo.it; mrava1@hotmail.com