Effect of cold storage on immediate graft function in an experimental model of renal transplantation in cats

Rebecca A. Csomos Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53706.

Search for other papers by Rebecca A. Csomos in
Current site
Google Scholar
PubMed
Close
 VMD, PhD
,
Robert J. Hardie Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53706.

Search for other papers by Robert J. Hardie in
Current site
Google Scholar
PubMed
Close
 DVM
,
Chad W. Schmiedt Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53706.

Search for other papers by Chad W. Schmiedt in
Current site
Google Scholar
PubMed
Close
 DVM
,
Fern A. Delaney Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53706.

Search for other papers by Fern A. Delaney in
Current site
Google Scholar
PubMed
Close
 BS
, and
Jonathan F. McAnulty Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53706.

Search for other papers by Jonathan F. McAnulty in
Current site
Google Scholar
PubMed
Close
 DVM, PhD

Abstract

OBJECTIVE To assess the effect of cold storage (CS) on immediate posttransplantation function of renal autografts in cats.

ANIMALS 15 healthy 1-year-old cats.

PROCEDURES Cats were assigned to 2 groups and underwent autotransplantation of the left kidney followed by nephrectomy of the right kidney. The left kidney was autotransplanted either immediately (IT group; n = 6) or after being flushed with a cold sucrose phosphate solution and stored on ice while the implant site was prepared (CS group; 9). Serum creatinine and BUN concentrations were monitored daily and autografts were ultrasonographically examined intermittently for 14 days after surgery.

RESULTS Mean duration of CS was 24 minutes for the CS group. Posttransplantation serum creatinine and BUN concentrations for the CS group had lower peak values, returned to the respective reference ranges quicker, and were generally significantly lower than those for the IT group. Mean posttransplantation autograft size for the CS group was smaller than that for the IT group.

CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that immediate posttransplantation function of renal autografts following a short period of CS was better than that of renal autografts that did not undergo CS, which suggested CS protected grafts from ischemic injury and may decrease perioperative complications, speed recovery, and improve the long-term outcome for cats with renal transplants.

IMPACT FOR HUMAN MEDICINE Cats metabolize immunosuppressive drugs in a manner similar to humans; therefore, renal transplantation in cats may serve as a desirable model for investigating the effects of renal transplantation in human patients.

Abstract

OBJECTIVE To assess the effect of cold storage (CS) on immediate posttransplantation function of renal autografts in cats.

ANIMALS 15 healthy 1-year-old cats.

PROCEDURES Cats were assigned to 2 groups and underwent autotransplantation of the left kidney followed by nephrectomy of the right kidney. The left kidney was autotransplanted either immediately (IT group; n = 6) or after being flushed with a cold sucrose phosphate solution and stored on ice while the implant site was prepared (CS group; 9). Serum creatinine and BUN concentrations were monitored daily and autografts were ultrasonographically examined intermittently for 14 days after surgery.

RESULTS Mean duration of CS was 24 minutes for the CS group. Posttransplantation serum creatinine and BUN concentrations for the CS group had lower peak values, returned to the respective reference ranges quicker, and were generally significantly lower than those for the IT group. Mean posttransplantation autograft size for the CS group was smaller than that for the IT group.

CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that immediate posttransplantation function of renal autografts following a short period of CS was better than that of renal autografts that did not undergo CS, which suggested CS protected grafts from ischemic injury and may decrease perioperative complications, speed recovery, and improve the long-term outcome for cats with renal transplants.

IMPACT FOR HUMAN MEDICINE Cats metabolize immunosuppressive drugs in a manner similar to humans; therefore, renal transplantation in cats may serve as a desirable model for investigating the effects of renal transplantation in human patients.

Contributor Notes

Dr. Csomos’ present address is Med-Vet Medical and Cancer Centers for Pets, 2611 Florida St, Mandeville, LA 70448.

Dr. Schmiedt's present address is the Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens, GA 30602.

Address correspondence to Dr. McAnulty (jonathan.mcanulty@wisc.edu).
  • 1. Fahner PJ, Idu MM, van Gulik TM, et al. Systematic review of preservation methods and clinical outcome of infrainguinal vascular allografts. J Vasc Surg 2006; 44:518–524.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 2. Jiao B, Liu S, Liu H, et al. Hypothermic machine perfusion reduces delayed graft function and improves one-year graft survival of kidneys from expanded criteria donors: a meta-analysis. PLoS One 2013; 8:e81826.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 3. Gregory CR, Bersteen L. Organ transplantation in clinical veterinary practice. In: Douglas SA, ed. Textbook of small animal surgery. 3rd ed. Philadelphia: WB Saunders Co, 2003;122–136.

    • Search Google Scholar
    • Export Citation
  • 4. Mehl ML, Kyles AE, Reimer SB, et al. Evaluation of the effects of ischemic injury and ureteral obstruction on delayed graft function in cats after renal autotransplantation. Vet Surg 2006; 35:341–346.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 5. Bernsteen L, Gregory CR, Pollard RE, et al. Comparison of two surgical techniques for renal transplantation in cats. Vet Surg 1999; 28:417–420.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 6. Schmiedt CW, Mercurio AD, Glassman MM, et al. Effects of renal autograft ischemia and reperfusion associated with renal transplantation on arterial blood pressure variables in clinically normal cats. Am J Vet Res 2009; 70:1426–1432.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 7. Belzer FO, Ashby BS, Dunphy JE. 24-hour and 72-hour preservation of canine kidneys. Lancet 1967; 2:536–538.

  • 8. Bartels-Stringer M, Kramers C, Wetzels JF, et al. Hypothermia causes a marked injury to rat proximal tubular cells that is aggravated by all currently used preservation solutions. Cryobiology 2003; 47:82–91.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 9. Ambiru S, Uryuhara K, Talpe S, et al. Improved survival of orthotopic liver allograft in swine by addition of trophic factors to University of Wisconsin solution. Transplantation 2004; 77:302–319.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 10. Amemiya H, Suzuki S, Niiya S, et al. Viability estimation of preserved dog kidneys based on the LDH activity in the preservation perfusate. Nihon Jinzo Gakkai Shi 1989; 31:643–649.

    • Search Google Scholar
    • Export Citation
  • 11. Belzer FO, Southard JH. Organ preservation and transplantation. In: Meryman HT, ed. Transplantation: approaches to graft rejection. New York: Alan R. Liss Inc, 1986;291–303.

    • Search Google Scholar
    • Export Citation
  • 12. McAnulty JF. Hypothermic storage of feline kidneys for transplantation: successful ex vivo storage up to 7 hours. Vet Surg 1998; 27:312–320.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 13. McAnulty JF, Reid TW, Waller KR, et al. Successful six-day kidney preservation using trophic factor supplemented media and simple cold storage. Am J Transplant 2002; 2:712–718.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 14. McAnulty JF, Vreugdenhil PK, Lindell S, et al. Successful 7-day perfusion preservation of the canine kidney. Transplant Proc 1993; 25:1642–1644.

    • Search Google Scholar
    • Export Citation
  • 15. Schilling M, Saunder A, Southard JH, et al. Five-to-seven-day kidney preservation with aspirin and furegrelate. Transplantation 1993; 55:955–958.

    • Search Google Scholar
    • Export Citation
  • 16. Pollard R, Nyland TG, Bernsteen L, et al. Ultrasonographic evaluation of renal autografts in normal cats. Vet Radiol Ultrasound 1999; 40:380–385.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 17. Rivers BJ, Walter PA, O'Brien TD, et al. Duplex Doppler estimation of Pourcelot resistive index in arcuate arteries of sedated normal cats. J Vet Intern Med 1996; 10:28–33.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 18. Rivers BJ, Walter PA, Polzin DJ, et al. Duplex Doppler estimation of intrarenal Pourcelot resistive index in dogs and cats with renal disease. J Vet Intern Med 1997; 11:250–260.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 19. Newell SM, Ellison GW, Graham JP, et al. Scintigraphic, sonographic, and histologic evaluation of renal autotransplantation in cats. Am J Vet Res 1999; 60:775–779.

    • Search Google Scholar
    • Export Citation
  • 20. Schmiedt CW, Delaney FA, McAnulty JF. Ultrasonographic determination of resistive index and graft size for evaluating clinical feline renal allografts. Vet Radiol Ultrasound 2008; 49:73–80.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 21. McArthur C, Geddes CC, Baxter GM. Early measurement of pulsatility and resistive indexes: correlation with long-term renal transplant function. Radiology 2011; 259:278–285.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 22. Parolini C, Noce A, Staffolani E, et al. Renal resistive index and long-term outcome in chronic nephropathies. Radiology 2009; 252:888–896.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 23. Lam FT, Mavor AI, Potts DJ, et al. Improved 72-hour renal preservation with phosphate-buffered sucrose. Transplantation 1989; 47:767–771.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 24. Beyer W. CRC standard mathematical tables. 28th ed. Boca Raton, Fla: CRC Press, 1989.

  • 25. Sutherland BJ, McAnulty JM, Hardie RJ. Ureteral papilla implantation as a technique for neoureterocystostomy in cats undergoing renal transplantation: 30 cases. Vet Surg 2016; 45:443–449.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 26. Halling KB, Graham JP, Newell SP, et al. Sonographic and scintigraphic evaluation of acute renal allograft rejection in cats. Vet Radiol Ultrasound 2003; 44:707–713.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 27. Kyles AE, Gregory CR, Wooldridge JD, et al. Management of hypertension controls postoperative neurologic disorders after renal transplantation in cats. Vet Surg 1999; 28:436–441.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 28. Southard JH. Improving early graft function: role of preservation. Transplant Proc 1997; 29:3510–3511.

  • 29. Veres G, Hegedüs P, Barnucz E, et al. Graft preservation with heparinized blood/saline solution induces severe graft dysfunction. Interact Cardiovasc Thorac Surg 2015; 20:594–600.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 30. Southard JH, Belzer FO. Control of canine kidney cortex slice volume and ion distribution at hypothermia by impermeable anions. Cryobiology 1980; 17:540–548.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 31. Amersi F, Shen XD, Anselmo D, et al. Ex vivo exposure to carbon monoxide prevents hepatic ischemia/reperfusion injury through p38 MAP kinase pathway. Hepatology 2002; 35:815–823.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 32. Southard JH, Lindell SL, Belzer FO. Energy metabolism and renal ischemia. Ren Fail 1992; 14:251–255.

  • 33. Southard JH, Lutz MF, Ametani MS, et al. Stimulation of ATP synthesis in hypothermically perfused dog kidneys by adenosine and PO4. Cryobiology 1984; 21:13–19.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 34. McAnulty JF, Southard JH, Belzer FO. Comparison of the effects of adenine-ribose with adenosine for maintenance of ATP concentrations in 5-day hypothermically perfused dog kidneys. Cryobiology 1988; 25:409–416.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 35. McAnulty JF, Ploeg RJ, Southard JH, et al. Successful five-day perfusion preservation of the canine kidney. Transplantation 1989; 47:37–41.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 36. Kim JS, Southard JH. Alteration in cellular calcium and mitochondrial functions in the rat liver during cold preservation. Transplantation 1998; 65:369–375.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 37. Southard JH, den Butter B, Marsh DC, et al. The role of oxygen free radicals in organ preservation. Klin Wochenschr 1991; 69:1073–1076.

  • 38. Southard JH, Senzig KA, Belzer FO. Effects of hypothermia on canine kidney mitochondria. Cryobiology 1980; 17:148–153.

  • 39. Stringham JC, Southard JH, Hegge J, et al. Limitations of heart preservation by cold storage. Transplantation 1992; 53:287–294.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 40. Southard JH, Marsh DC, McAnulty JF, et al. Oxygenderived free radical damage in organ preservation: activity of superoxide dismutase and xanthine oxidase. Surgery 1987; 101:566–570.

    • Search Google Scholar
    • Export Citation
  • 41. Tullius SG, Heemann UW, Azuma H, et al. Alloantigen-independent factors lead to signs of chronic rejection in long-term kidney isografts. Transpl Int 1994; 7(suppl 1):S306–S307.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 42. Paul LC. Pathophysiology of chronic renal allograft rejection. Transplant Proc 1999; 31:2715–2716.

  • 43. Matas AJ, Humar A, Gillingham KJ, et al. Five preventable causes of kidney graft loss in the 1990s: a single-center analysis. Kidney Int 2002; 62:704–714.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 44. Kasiske BL. Clinical correlates to chronic renal allograft rejection. Kidney Int Suppl 1997; 63:S71–S74.

  • 45. Heemann UW, Tullius SG, Azuma H, et al. The relationship between reduced functioning kidney mass and chronic rejection in rats. Transpl Int 1994; 7(suppl 1):S328–S330.

    • Crossref
    • Search Google Scholar
    • Export Citation

Advertisement