Our Research Achievements

1. With colleagues we have defined the impediments to deceased organ donation in NSW. (1,2,3,4,5)

Applications

• A software programme for the measurement of potential organ donors has been successfully introduced in Australia and the UK.
• This programme has helped intensive care specialists and organ donor coordinators to build an exemplary organ donation programme in the HNELHD which has achieved the highest yearly donor rate in NSW for the last 4 years.

2. We have found a molecule, an integrin αvβ6 that is expressed in the kidney when it is injured. (6)

Application

• It can be used to study ischaemia reperfusion injury in transplanted kidneys with a view to testing treatments that may minimize the injury.

3. We have developed a web based point of clinical care software programme called Transnet for transplantation, dialysis and renal medicine; it has replaced the paper record.

Applications

• It improves the standard of clinical transplant care by providing accurate and complete data on line, by improving staff communication and by enabling linkage to rural districts.
• It allows us to analyse our performance and answer our clinical research questions.

4. With colleagues we have found a novel transplant immunosuppressive agent, Castanospermine that impairs rejecting cells binding to the blood vessels and entering the transplant. (7, 8) It works in partnership with cyclosporin A or tacrolimus, standard immunosuppressive agents.

Applications

• It may be used in transplantation because it reduces the toxicity of cyclosporine or tacrolimus by reducing the drug dose.
• It may be used to reduce ischaemia reperfusion injury.

5. We have found that transplant recipients who have been treated with immunosuppressive agents before transplantation have an increased risk of contracting four different cancers during transplantation. (9, 10)

Applications

• Prospective recipients should be informed of these risks before any immunosuppressive drug treatment.
• Just like vaccination against cervical cancer, vaccines need to be developed against two cancer inducing viruses in transplantation – EBV and HPV.

6. Tolerance in transplantation is the “holy grail” as it would remove the need for immunosuppressive drugs. We have evidence that it may be related to the inability of antibodies in the recipient to bind complement. (11) We have also found that well established transplant recipients excrete increased levels of a product from cells necessary for tolerance. (12)

Application

• Monitoring of transplant recipients for markers of tolerance with a view to detecting tolerant recipients is in progress.

7. We have found that unexpected compression of renal transplants early after the operation can lead to their loss. (13)

Application

• We have developed a surgical technique to prevent this happening.

8. With colleagues we have shown that deposition of a complement derivative in the glomerulus (or filter) in the transplanted kidney carries a poor outlook and is probably a rejection event. (14)

Application

• Further evaluation of these findings is proceeding as early detection of glomerular rejection may herald better transplant outcomes.

9. By a randomized controlled we established that a generic derivative of cyclosporin A was a safe effective substitute for the standard drug in stable renal transplant recipients. (15)

Application

• This study facilitated the introduction of generic derivatives of standard immunosuppressive drugs in transplantation for the first time in Australia. Cost savings followed and these were reinvested in information technology for transplantation in our own transplant programme.

10. We have diversified the source of kidneys available for transplantation: we are the first Unit in Australia to successfully transplant against a positive T cell cross match (1999); first in NSW to successfully transplant across an ABO incompatible barrier (2006); second in Australia to successfully transplant kidneys after cancer excision (2009); and, we led the initiative to introduce non directed renal donation in NSW (started in 2008).

Application

• Transplant rates are increased by these successful procedures: lives are saved, long term costs reduced and patients released from dialysis.
• Other transplant units in Australia have benefited from this expertise.

References

1. Hibberd AD, Pearson IY, McCosker CJ, Chapman JR, Macdonald GJ, Thompson JF, O’Connell DL, Mohacsi PJ, McLoughlin MP, Spratt PM, Compton JS, Brown MA. The potential for cadaveric organ retrieval in New South Wales. BMJ 1992; 304:1339-43.
2. Thompson JF, Hibberd AD, Pearson IY, McCosker CJ, Chapman JF, Macdonald GJ, O’Connell DL, Mohacsi PJ, McLoughlin MP, Spratt PM, Compton JS, Brown MA. Can the demand for renal transplantation be met? Transplant Proc 1992; 24: 2270-1.
3. Chapman JR, Hibberd AD, McCosker C, Thompson JF, Ross W, Byth P, Macdonald GJ. Obtaining consent for organ donation in nine NSW metropolitan hospitals. Anaesthesia and Intensive Care. 1995; 23: 81-7.
4. Thompson JF, Hibberd AD, Mohacsi PJ, Chapman JR, Macdonald GJ, Mahony JF. Can cadaveric organ donation rates be improved? Anaesthesia and Intensive Care. 1995; 23: 99-103
5. Thompson JF, McCosker CJ, Hibberd AD, Chapman JF, MacDonald GJ, O’Connell DL, Mohacsi PJ, Spratt PM, Mahoney J. Identification of the cadaveric potential organ donors in New South Wales. Anaesthesia and Intensive Care. 1995; 23: 75-80.
6. Trevillian PR, Paul H, Millar E, Hibberd AD, Agrez MV αv β6 integrin expression in diseased and transplanted kidneys. Kidney international 2004; 66:1423-33.
7. Grochowicz PM, Hibberd AD, Bowen KM, Clark DA, Cowden WB, Willenborg DO. Castanospermine an oligosaccharide processing inhibitor reduces membrane expression of adhesion molecules and prolongs heart allograft survival in rats. Transplant Immunology 1996; 4: 275-285.
8. Hibberd AD, Clark DA, Trevillian PR, Mcelduff P, Cowden WB. Castanospermine, an oligosaccharide processing inhibitor reduces lymphocyte – endothelial cell binding and the membrane expression of adhesion molecules. Transplant Immunology 2012; 27: 39-47.
9. Hibberd AD, Trevillian PR, Wlodarcyzk JH, Stein AM, Gillies AHB, Sheil AGR, Disney APS. Predialysis immunosuppression is an independent risk factor for some cancers in renal transplantation. Transplant Proc 2001; 33: 1846-1847.
10. Hibberd AD, Trevillian PR, Wlodarczyk JH, Kemp, D, Heer MK, Stein AM Gillies AH, Sheil AGR. The Effect of Immunosuppression for Primary Renal Disease upon the Risk of Cancer in Subsequent Renal Transplantation: a Population Based Retrospective Cohort Study. Transplantation 2012 (in press).
11. R Cervantes, PR Trevillian, B Young, AD Hibberd. Clinical Recovery from Acute antibody mediated rejection and chronic antibody mediated rejection is associated with early loss of C1q fixation by class II donor specific antibodies. Transplantation Society Australia and New Zealand June 2012. Immunology and Cell Biology 2012 (abstract).
12. Wong M, Scott R, Hibberd AD, Trevillian PR, Clark D, Meldrum C. Measurement of Foxp3 gene expression in renal transplant recipients. Transplantation Society of Australia and New Zealand, June 2011. Immunology and Cell Biology 2011 (abstract).
13. Heer MK, Hibberd AD, Trevillian PR, Hardy DB. Salvage of kidneys with renal transplant compartment syndrome. Transplant International 2012; 25: e47-e49.
14. Vilayur E, Trevillian P, Nanra R, Gillies A, Heer M, Hibberd AD. A systematic study of linear C4D deposition in glomerular capillary loops in renal transplant biopsies. The Transplantation Society August 2008 Transplantation 2008 (abstract).
15. Hibberd AD, Trevillian PR, Roger S D, Wlodarczyk JH, Stein AM, Bohringer EG, Milson Hawke SM Assessment of the bioequivalence of a generic derivative of cyclosporin A by a randomized controlled trial in stable renal transplant recipients. Transplantation 2006; 81 (5); 711- 7.