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There
are numerous hot topics with regards to kidney grafts optimal preservation,
assessment of condition and recondition. This is reflected on the amount of the
relevant literature. Unfortunately, lots of the questions remain without a
definite answer. All the research focuses in improving our understanding of
preservation as well as on identifying ways for ex vivo real-time assessment of
grafts condition while attempting to improve it. The progress made over the
last few decades is impressive. Starting from static cold storage as the only
mode of preservation and then moving to the dynamic methods and their versions
followed by analysis of the perfusate, measurement of the flow, perfusion
pressure and resistance etc. Moreover, use of imaging such as Doppler ultrasonography
and renal scintigraphy   or dynamic MRI has been proposed to assess
graft’s function pre-retrieval or ex-vivo.

 

Furthermore,
biopsy parameters have been shown to be important too and composite scores
combining donors’ comorbid status with renal function parameters and
histological scoring or even clinical donor risk scores are more accurate.
Additionally, advancements in organ reconditioning include “organ painting”,
use of serine plasma proteases, administration of heparin or other pharmacological
manoeuvres. Gene therapy and stem cells have also been recently utilised to
improve those marginal organs. However, despite the above, the kidney
transplant lists are growing faster than the donors, therefore the pressure on
demand for grafts is of a considerable amount.  

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There
are significant questions with regards to the optimal way of kidney
preservation, assessment of condition and recondition.

–         
What is the optimal graft?

–         
Who should be offered the ECD kidneys? How far
the criteria can be expanded?

–         
Which kidney benefits more from MP? What the
settings should be?

–         
What is the optimal perfusion fluid composition?

–         
What is the best tool for assessment of organ
condition?

–         
Are the above methods  cost – effective? 

–         
What are the methods of reconditioning and their
current limitations?

–         
Is the use of stem cells or gene therapy always
beneficial / ethical?

–         
Are the above ethical or significantly
interfering with mother nature?

–         
Are there other ways to improve outcomes on
kidney transplantation (further reduction of warm ischaemia time,
pharmacological agents, supporting haemofiltration, advancements in
immunosuppression etc).

–         
Are there other novel methods of treatment of
renal failure etc that will make need for transplantation less favourable? 

 

Undoubtedly, end-stage renal failure incidence has
increased   over the last decades. On the
other hand, there is full agreement that renal transplantation is cost
effective, prolongs survival and offers an improved quality of life when
compared to dialysis. To reduce the wait for a renal transplant multiple
strategies are being used. The above mentioned strategies include those with focus; to slow the progression of chronic
kidney disease addressing the causative risk factors, treating other
pre-existing contributing pathologies, early diagnosis, optimisation of
monitoring, to increase the number of kidney transplants increase awareness,
ECD, living donors, paid donation, to 
increase graft survival and eliminate transplant losses improved
preservation methods, ways of assessing their condition, pathways for
reconditioning etc,   to improve organ
allocation and post-transplant management Age, sex, human leukocyte antigen
matches, better understanding of delayed graft function, immunosuppression,
nonadherence, malignancies, chronic allograft nephropathy, new onset diabetes
after transplant etc.

 

Ethical aspects in renal transplantation inevitably
are important too. Living donor
transplantation is currently considered an established treatment for end-stage
renal failure and is acceptable nationally and internationally, while
supervising and safeguarding the safety of the donation, information, motivation,
consent and ensuring the absolute absence of profit. Other important decisions
are   related to renal transplantation from
prediabetic living donors or from ECD. This is because outcomes of ECD kidney transplants are known to be superior to dialysis
but clearly inferior to transplant with a standard donor. Similar with
prediabetic living donors. Living kidney donation is complex process and
includes psychiatric implications etc. The ethical issues may vary based on the
form of organ donation; whether it is living-related, living-unrelated, cadaveric,
or from brain-dead individuals. As expected allocation of organs may be
considered as an ethical dilemma too as there may be several burdens around
it.  Information on confidentiality of
donor, fairness and equity in donor selection processes, and access to kidney
transplantation lists etc are huge issues too.

 

Organ
preservation, assessment of condition and recondition also have significant
ethical background. How far are we allowed to go? Is it against natural
selection the use of gene therapy and stems cells? What can the consequences of
the above be? Are we allowed to administer treatment / perform imaging and
other diagnostic modalities to a dying donor in order to optimise his organs
prior to retrieval without benefits for him? Can we discard grafts based on
non-accurate and established yet methods of condition?

 

Taking into
consideration the above, currently it seems that machine perfusion is an agreed
prospect of renal graft preservation, assessment of condition and recondition.
The optimal pressure settings will be identified after intense studies as well
as the ideal perfusate and urine biomarkers. Rapid sample microdialysis and
other techniques will be developed further for accurate real-time measurement
of the above. Imaging modalities use as well as rapid histopathology
examination will assist in accurate assessment of the graft, prediction of its
function and its post transplantation outcome. Similarly, the gold standard
perfusion solution will be found sooner rather than later. What about an early
reperfusion with recipient’s filtrated and nutrient-enriched blood? Further
studies are urgently needed. Moreover, use of gene therapy and stem cells ex
vivo will give us the opportunity to control ischaemia reperfusion cascade and
improve not only borderline grafts but even standard ones. Pharmacological
agents can ensure that if administered ex vivo will cease the cellular ischaemic
injury and its effects, preserve the vasculature and ultimately the grafts
functional status.

 

Clearly, the forthcoming
decade is expected to bring interesting and important advances in the field of
organ transplantation. However, only time will tell whether 

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