Renal transplantation

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Renal transplantation (renal allograft transplantation) is a radical, life-saving procedure used in primarily young and middle-aged dogs with existing terminal renal disease that is non-neoplastic, non-infectious and an alternative to continuous renal dialysis.

This procedure is less successfully employed than in feline transplantation.

First described as a canine procedure in 1902[1], the techniques have not significantly improved until Drs Clare Gregory and Gary Gourley pioneered new techniques in the late 1980s that made this technique clinically feasible[2].

This procedure is highly technically advanced, expensive and is usually reserved for younger canine candidates. Also complicating the use of this procedure is the underlying ethical considerations of donor dogs and the cost-benefit ratio in middle-aged and older dogs versus euthanasia.

In dogs with azotemia and creatinine levels > 30mg/dL that are non-responsive to hemodialysis may be considered candidates if a specialty referral centre is avaialable to perform the procedure.

Indications for renal transplantation include:

Contraindications in candidate dogs include pre-existing heart diseases, metastatic non-renal neoplasia and infectious viral diseases.

Recipients are also routine tested for evidence of parasites, distemper, parvovirus, adenovirus type 2, para-influenza virus, corona virus, rabies and canine papilloma virus[3].

Suitable donors are then tissue-typed with the recipient using microsatellite markers within DLA class I and class II regions[4].

The procedure involves use of a donor kidney which is usually implanted in the caudal abdomen and stabilized using a transverse abdominis muscle flap, which is raised from the abdominal wall and sutured to the renal capsule.

Blood supply to the donor kidney is established through surgical anastomosis of the donor artery and vein to the recipients vasculature (caudal abdominal aorta and vena cava) in an end-to-side anastomosis.

Urine drainage is established by implantation of the ureter into the urinary bladder.

With few exceptions, the native kidneys are not removed in order to allow residual renal function should the allograft die or become dysfunctional due to ischemia/reperfusion injury[5].

Dogs appear to have a high incidence of intussusception following transplantation, which is obviated by enteroplication of the adjacent intestines and use of intraoperative opioid administration.

Post-operative complications include ureteral stenosis, thromboembolism, glomerulonephritis and allograft rejection[6]. Allograft rejection can be monitored by surveillance biopsies or by abnormal laboratory and/or hemodynamic data[7].

Long-term chemotherapy combinations of cyclosporine, azathioprine, capecitabine[8] and prednisolone are required to prevent organ rejection[9][10]. The use of ascorbic acid have been shown to reduce the risk of post-operative renal ischemia and should be considered[11].

Ketoconazole has been shown to be of benefit in some dogs at reducing doses of cyclosporine, but may cause hypoalbuminemia, weight loss and hepatotoxicity[12].

An experimental protocol has been devised using immunological tolerance involving myoablative (whole body) irradiation followed by concurrent donor bone marrow and renal allograft transplantation. Immunosuppressive drugs are then administered initially after transplantation and eventually tapered[13].

In donor dogs, long-term renal complications are uncommon as they are usually thoroughly tested prior to renal donation[14].

Current canine renal transplantation in clinical patients is associated with a high morbidity and mortality (approximately 50% within the first 2 months).

References

  1. Ulmann E (1902) Experimentelle Nierentransplantation. Wien Klin Wochenschr 11281:285
  2. Adin, CA (2009) Renal transplantation. In Kirk's curent veterinary therapy XIV. Saunders Elsevier, St. Louis, Missouri. pp:901-906
  3. Graves SS et al (2007) Stable trichimerism after marrow grafting from 2 DLA-identical canine donors and nonmyeloablative conditioning. Blood 110(1):418-423
  4. Wagner JL et al (1996) Histocompatibility testing of dog families with highly polymorphic microsatellite markers. Transplantation 62:876–877
  5. Polyak MM & Grosche A (2008) Comparison of Vasosol and University of Wisconsin solutions on early kidney function after 24 hours of cold ischemia in a canine autotransplantation model. J Surg Res 150(2):255-260
  6. Hopper K et al (2012) Outcome after renal transplantation in 26 dogs. Vet Surg 41(3):316-327
  7. Parsonnet V et al (2007) Detection of early renal transplant rejection by minimally-invasive monitoring of impedance variability. Biosens Bioelectron 22(11):2749-2753
  8. Milovancev M et al (2007) Use of capecitabine to prevent acute renal allograft rejection in dog erythrocyte antigen-mismatched mongrel dogs. Vet Surg 36(1):10-20
  9. Nam HS et al (2008) Gingival overgrowth in dogs associated with clinically relevant cyclosporine blood levels: observations in a canine renal transplantation model. Vet Surg 37(3):247-253
  10. Zarfoss M et al (2007) Histopathologic evidence of capecitabine corneal toxicity in dogs. Vet Pathol 44(5):700-702
  11. Lee JI et al (2006) Attenuation of ischemia-reperfusion injury by ascorbic acid in the canine renal transplantation. J Vet Sci 7(4):375-379
  12. Katayama M et al (2010) Fluconazole decreases cyclosporine dosage in renal transplanted dogs. Res Vet Sci 89(1):124-125
  13. Kuhr CS et al (2007) Long-term tolerance to kidney allografts in a preclinical canine model. Transplantation 84(4):545-547
  14. Urie BK et al (2007) Evaluation of clinical status, renal function, and hematopoietic variables after unilateral nephrectomy in canine kidney donors. J Am Vet Med Assoc 230(11):1653-1656