Abstract

Renal transplantation is the definitive treatment for the end-stage renal failure.
Despite concerted efforts to increase the number of available organs there
remains a wide gap. Kidneys with small renal cell carcinoma have been used
for transplantation after ex vivo resection of tumours with excellent results.
Concerns regarding the behaviour of tumour under standard
immunosuppression prevent this source from being popularised. We studied
tumour behaviour with standard immunosuppression and immunosuppressives
with anti-proliferative properties and the effect of MHC matching on tumour
behaviour. Luciferase labelled Wistar rat kidney tumour cells were injected
subcutaneously into Wistar or Lewis rats to mimic well and poorly matched
groups. These were divided into groups receiving Cyclosporine, Sirolimus high
and Sirolimus low dose and Leflunomide. Effects of matching on tumour
rejection were studied by immunosuppression withdrawal in half of the animals
within each group. Tumour progression was monitored with IVIS spectrum
imaging system.
When the immunosuppression was continued for the length of the study period
with Cyclosporine immunosuppression, the tumour continued to grow in both
strains. With high dose Sirolimus, the tumour was eradicated within 2 weeks in
both Wistar and Lewis rats (p <0.05). Both strains receiving low dose Sirolimus
also eradicated the tumour within four weeks of treatment (p <0.05). In
Leflunomide group, 4/7 animals rejected the tumour within the 4 weeks of
study period (p <0.05).
To study the effects of rejection and matching on the tumour behaviour, the
immunosuppression was stopped after 2 weeks of treatment and the animals
followed for another two weeks to study these effects. After treatment
withdrawal, the tumour rejection was noted which was significantly stronger in
poorly matched animals than in well-matched animals (p <0.05) in cyclosporine
treated animals.
These results appeared to be in line with our hypothesis, that newer
immunosuppressive medications with anti-neoplastic effects may be better
options after transplanting kidneys after small tumour ex-vivo resection.
Acute rejection showed significant ability to lead to tumour eradication, more
effectively in less well-matched animals than well-matched combinations. Thus
perhaps clinically, recipients of such restored kidneys should be less well
matched and immunosuppressed with agents with anti-proliferative properties.
These results will need to be replicated with further studies including closely
monitored clinical studies before it can be popularised at a significant new
source of precious organs.