This document provides information on kidney transplantation and organ preservation techniques. It discusses: - The shortage of donor organs compared to demand for transplantation. Donors can be living or deceased. - Methods for preserving organs including static cold storage, hypothermic machine perfusion, normothermic regional perfusion, and normothermic machine perfusion. Preservation aims to suppress metabolism and minimize injury during storage. - Factors that can damage donor organs including brain death, circulatory death, warm ischemia, and reperfusion injury upon transplantation. - Commonly used preservation solutions like University of Wisconsin, HTK, and Celsior and their mechanisms of action. - Guidelines for maximum cold ischemia times

1. KIDNEY
PRESERVATION
Dr. Praveen. B
Institute of Urology
MMC & RGGGH

2. Allograft Renal Transplantation
■ Treatment of choice for ESRD.
■ Successful kidney transplantation can be expected to significantly increase a
patient’s quality of life.
■ History

3. Organ Donation
■ The number of organs required to satisfy the needs of transplantation far
exceeds the number of donor organs available.

4. Donors
■ Living Donors
■ Deceased Donors
– Donation after Brain death ( Brain stem dead, heart beating donors)
– Donation after Circulatory death

5. DBD Donors
■ Standard Criteria Donors ( SCD)
– Under 50 yrs old
■ Expanded Criteria Donors (ECD)
– Over 60 yrs old
– 50-69 yrs old with atleast two of the following
■ Hypertension
■ Cerebrovascular cause of brain death
■ Pre retrieval Serum Creatinine >1.5mg/dl

6. DCD Donors
■ Maastricht Criteria

7. Overcoming shortage of organs
■ Maximising DBD donation
■ Use of Marginal or Extended criteria DBD donors
■ Use of DCD donor
■ Increased Living donor transplantation

8. Graft Injury in Transplant
ISCHEMIA
REPERFUSION

10. Organ damage after Brain death
■ Cerebral injury and brain death are associated with the release of
cytokines and the initiation of inflammatory processes that can directly injure
organs
■ Can lead to further immune damage at reperfusion in the recipient.
■ Hormonal changes after brain death include reduced levels of antidiuretic
hormone and thyroid hormones
■ Myocardial suppression and decreased vascular tone results in hypotension and
inadequate perfusion of organs.
■ Kidneys – Inflammatory cytokines can lead to necrosis of renal tubules and
fibrous proliferation of the arterial intima.

11. Organ damge after Circulatory Death
■ Organs from DCD are exposed to inflammatory cytokines, but in a less
profound way to DBD
■ Undergo a significant period of warm ischemia before retrieval

12. Metabolic derangements
■ When a kidney is removed from the donor’s body, perfusion completely ceases,
leading to an absence of oxygen and nutrient delivery to the renal cells, which
will rapidly lead to serious metabolic problems.
■ Suppression of metabolism is therefore essential to maintain organ viability
during the preservation period

13. Why Preservation?
■ Preservation BUYS TIME!!!
■ Good organ preservation – Major determinant of Graft outcome after
Revascularisation

14. Key - Suppression of metabolism
■ Suppression of metabolism is essential to maintain organ viability
■ Reduction of the core temperature of the kidney below 4°C will result in a
reduction of metabolism to 5% to 8% and will diminish enzyme activity
■ Cold Storage is the key

15. Deleterious effects of Cold Storage
Classic unwanted side effects of hypothermia are
■ swelling,
■ acidosis,
■ altered intracellular enzyme activity
■ Production of radical oxygen species upon reperfusion.
– Xanthine oxidase – a well studied generator of ROS

17. Aims of modern kidney storage
solutions
■ Control of cell-swelling during hypothermic ischaemia
■ maintenance of intra- and extra-cellular electrolyte gradient during ischaemia
■ buffering of acidosis
■ provision of energy reserve
■ minimisation of oxidative reperfusion injury.
■ There is no agreement on which of the mechanisms is most important for post-
ischaemic renal graft function

18. Modern Storage solutions
■ Eurocollins solution
■ University of Wisconsin Solution
■ HTK solution
■ Celsior solution

20. Eurocollins solution
■ Phosphate as pH Buffer
■ Glucose as Osmotic agent

22. University of Wisconsin solution
■ Cell impermeant agents (lactobionic acid, raffinose, hydroxyethyl starch)
– prevent the cells from swelling during cold ischemic storage
■ Glutathione, adenosine, Allopurinol
– stimulate recovery of normal metabolism upon reperfusion
– Free radical scavenging

24. HTK – Histidine, Tryptophan,
Ketoglutarate
■ Histidine – as potent buffer
■ Tryptophan – as membrane stabilizer and anti-oxidant
■ Ketoglutarate – improve ATP production during reperfusion
■ K+ - 9

25. Celsior

26. Celsior
■ Lactobionic acid, Mannitol – Impermeant
■ Histidine – pH buffer
■ Adenosine – ROS scavenging

27. ■ No storage solution seems to combine all mechanisms.
■ For living donors, in whom immediate kidney transplantation is planned,
perfusion with crystalloid solution is sufficient.
■ Kidneys coming from DCD donors, especially those uncontrolled, are high-risk
marginal organs due to prolonged warm ischaemia periods, and require specific
measures in order to diminish the rate of nonfunction or DGF.
■ Previously, Euro-Collins was widely used, but is no longer recommended.
■ Presently, University of Wisconsin (UW), and histidine-tryptophan-ketoglutarate (HTK) solution
are equally effective and are standard for multi-organ or single kidney harvesting procedures.
■ University of Wisconsin solution has been the standard static cold preservation solution for the
procurement of liver, kidney, pancreas, and intestine
■ University of Wisconsin, HTK, and Celsior solutions have provided similar allograft outcomes in
most clinical trials;
■ In experimental studies of kidney preservation, HTK and UW retained a greater capacity to
preserve endothelial structure and pH buffering function during warm ischaemia in comparison
to Celsior, especially in uncontrolled DCD donors

28. EAU GUIDELINES 2021

29. Duration of Organ Preservation
■ Cold ischaemia time should be as short as possible.
■ Kidneys from ECDs after brain death (DBD) and DCD donors are more sensitive
to ischaemia than standard criteria donors.
■ Kidneys from DBD donors should ideally be transplanted within a 18 to 21
hour time period
■ There is no significant influence on graft survival within a 18 hour CIT
■ Kidneys from DCD donors should ideally be transplanted within 12 hours
■ kidneys from ECDs should ideally be transplanted within 12 to 15 hours

30. Methods of Preservation
■ Static
■ Dynamic

31. Static Cold Storage
■ Kidneys are flushed through the renal artery with a preservation fluid until
donor blood is completely cleared.
■ The kidney is then packaged in a sterile bag of this fluid and kept on ice in a
cool box. 2-4 deg

32. Dynamic Preservation
■ Dynamic preservation could allow for organ optimisation, offering a platform
for viability assessment, active organ repair and resuscitation.
■ Ex situ machine perfusion and in situ regional perfusion in the donor are
emerging as potential tools to preserve vulnerable grafts

33. Hypothermic Machine Perfusion
■ The retrieved kidney is placed within a chamber filled with chilled
preservation solution surrounded by an ice box.
■ The renal artery is cannulated by one end of a system of tubing, and a
pump is used to generate a pulsatile or continuous flow of preservation
solution through the renal vessels.
■ The fluid pours from the renal vein into the reservoir where the pump collects
it again to recirculate it

36. ■ The largest RCT comparing simple CS with HMP of deceased donor kidneys
showed an overall reduced risk of DGF and a survival benefit, most
pronounced in ECD kidneys with HMP
■ HMP from type III DCD donors decreased DGF with no impact on graft survival
■ Reduces the risk of DGF in standard criteria DBD donor kidneys regardless of
CIT

37. Normothermic Regional Perfusion
■ An extracorporeal circuit via arterial and venous - femoral or distal aortic and
vena cava cannulation to recirculate the donor blood and isolates the
abdominal compartment by occluding the descending aorta
■ The extra-corporeal circuit includes an oxygenator, a heat exchanger, a
centrifugal pump, and an open circuit with a reservoir

39. ■ Optimal duration of NRP is yet to be determined but around 120 minutes
appears to be sufficient to restore the cellular ATP
■ One of the key benefits of NRP is the real-time, in situ, dynamic assessment of
organ function ( via composite measurement of blood gases and biochemistry
every 30 minutes while on the pump)

41. ■ High incidence of DGF in category II DCD donors
■ an excellent 1-year Graft survival of 87.5%
■ The use of NRP led to a 27% reduction in the incidence of DGF compared
with in situ cold perfusion.
■ It has been advocated that NRP should become a standard method for
organ recovery from DCD in the future years

42. Normothermic Machine Perfusion
■ Normothermic machine perfusion (NMP) is based on the assumption that the most
effective means of preserving an organ is to replicate its physiologic milieu.
■ There is limited clinical experience of NMP in kidney transplantation to date
■ postulated benefits of normothermic perfusion as a means of preservation are:
– Restoration of cellular energy, repair of donation/retrieval injury,
minimization of ischemia-reperfusion;
– Measurement of viability;
– Delivery of organ-specific therapies; and
– Prolonged storage.

44. NATIVE KIDNEY NEPHRECTOMY
■ Careful selection of patients
■ Preservation of residual renal function for patients on dialysis can limit
the need for fluid and dietary restrictions.
■ Preservation Improves the management of hypertension and reduce the
risk for cardiac complication
■ Indication for native nephrectomy must be balanced by the risk of
observation

45. When to do?
■ If the Potential recipient has a living donor, it is ideal to perform
nephrectomy at least 6 weeks before the scheduled transplant.
■ Some surgeons prefer to do the nephrectomy at the time of transplant,
but this may increase the risk for complications with the transplant
kidney.
■ For patients who do not have a living donor, the timing of pretransplant
nephrectomy should be based on
– the indication,
– residual urine output, and
– accumulated wait list time.

46. Indications
■ Symptomatic renal stones not cleared by minimally invasive techniques or lithotripsy
■ High-grade solid renal tumors with or without acquired renal cystic disease
■ Polycystic kidneys that are
– symptomatic,
– extend below the iliac crest,
– have been infected, or
– have solid tumors
■ Persistent anti–glomerular basement membrane antibody levels
■ Significant proteinuria not controlled with medical nephrectomy or angioablation
■ Recurrent pyelonephritis
■ Grade 4 or 5 vesicoureteral reflux with urinary tract infections

47. Thank you