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Kidney Preservation: method and trends
This document summarizes different methods of kidney preservation for transplantation, including static cold storage and hypothermic machine perfusion. Static cold storage has traditionally been the main method, involving cooling and storing kidneys in preservation solutions. However, machine perfusion may provide advantages like reducing delayed graft function, especially for expanded criteria donors. While both methods aim to minimize damage during cold storage, machine perfusion allows monitoring and restoring organ viability before transplantation. Future areas of research include evaluating marginal kidneys and predicting transplant outcomes through biomarkers and other machine perfusion techniques.
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Similar to Kidney Preservation: method and trends
Kidney Preservation: method and trends
- 1. JOURNAL REVIEW KIDNEYPRESERVATION: METHODS AND TRENDS Keith Tsui, Daniel Wong, Kenneth Kwok, Patrick Tsai, Bernard Yung
- 2. Outline • Historyof kidney preservation • Static Cold Storage (SCS) • Hypothermic Machine Perfusion (HMP) • SCS vs HMC • Conclusion
- 3. Organ transplantation •Major advances in latter half of the 20th century • Only curative treatment for end-stage organ failure in many cases
- 4. Deceased Donor Types • Donation after brain death (DBD) • Standard criteria donors (SCD) Under 50 years old • Expanded criteria donors (ECD) Over 60 years old OR Aged 50-59 years old with at least 2 of the following: • Hypertension • Cerebrovascular cause of brain death • Pre-retrieval serum creatinine level > 1.5 mg/dL (132.6umol/L) • Donation after circulatory death (DCD) Metzger RA, Delmonico FL, Feng S, et al. Expanded criteria donors for kidney transplantation. Am J Transplant. 2003
- 5. Kidney transplant 1.Retrieving the organ from donor 2. Preserving the kidney 3. Implantation in the recipient
- 6. Why organ preservation? Preservation buys “time” Good organ preservation is a major determinant of graft outcome after re-vascularisation Organ Preservation: Current Concepts and New Strategies for the Next Decade; Transfus Med Hemother. Apr 2011
- 7. Methods of OrganPreservation • Static Cold Storage (SCS) • Dynamic Preservation • Hypothermic machine perfusion (HMP) • Normothermic machine perfusion • Oxygen persufflation
- 8. KIDNEY PRESERVATION StaticCold Storage
- 9. Kidney Preservation Warm ischaemic time in donor Cold ischaemic time Warm ischaemic time in recipient
- 10. Static Cold Storage(SCS) • First used in 1969, with Collins solution • Mainstay method of preservation for kidneys, livers, and others • Tackle problems during cold ischaemic time preservation possible up to 24 hours or longer “Preservation Solutions for Static Cold Storage of Kidney Allografts: A Systematic Review and Meta-Analysis”, American Journal of Transplantation 2012
- 11. Static Cold Storage(SCS) •Wash with sterile hypothermic preservation solution • Kidney core temperature 0-4oC • Store in ice water Image source: St. Louis Public Radio
- 12. In ischaemic condition… No Oxygen Intracellular ATP depletion Impaired Na/K ATPase Passive inflow of Na Water influx Cell swelling and damage Anaerobic respiration Lactic acid builds up Activate intracellular enzymes Lysosomal damage Na/Ca exchange Build up of intracellular Ca “Kidney Preservation: Review of Present and Future Perspective”, Transplantation Proceedings 2013
- 13. Principles used inSCS 1. Hypothermia decrease kinetics of metabolic activities 2. Specific solutions preserve intracellular environment in the absence of Na+/K+ pumps 3. High osmolarity in solutions reduce cell swelling 4. Remove free radicals “Preservation methods for kidney and liver”, Organogenesis 2009
- 14. Advantages of SCS • Cheaper - 1L UW solution: £116 (~HKD$1500) - LifePort kidney transporter x1: £10,700 (~HKD$135,000) + other costs Nice Guideline 2010 • Technically easier
- 15. Disadvantages of SCS • No standardised parameters to evaluate: 1. organ viability 2. ischaemic damage predictors of post-transplant outcomes
- 16. KIDNEY PRESERVATION TheSolutions
- 17. EC, Eurocollins UW,University of Wisconsin HTK, histidine-tryptophan-ketoglutarate;
- 18. Euro-Collins solution •Phosphate- as pH buffer •Glucose - as osmotic agent Preservation methods for kidney and liver; Organogenesis. 2009
- 19. EC, Eurocollins UW,University of Wisconsin HTK, histidine-tryptophan-ketoglutarate;
- 20. UW solution •Cell impermeant agents (lactobionic acid, raffinose, hydroxyethyl starch) • prevent the cells from swelling during cold ischemic storage • Glutathione and adenosine • stimulate recovery of normal metabolism upon reperfusion Organ Preservation; Annual Review of Medicine; Vol. 46
- 21. EC, Eurocollins UW,University of Wisconsin HTK, histidine-tryptophan-ketoglutarate;
- 22. Histidine-Tryptophane-Ketoglutarate (HTK)** •Histidine – as potent buffer •Tryptophan – as membrane stabilizer and anti-oxidant • Ketoglutarate – improve ATP production during reperfusion
- 23. KIDNEY PRESERVATION MachinePerfusion
- 24. Original method ofpreservation • Replaced by SCS due to development of preservation solutions as a cheaper alternative Photo from Kidney Transplant: Principles and Practice
- 25. Resurgence of interest • Changes in donor pool • US • ECDs increased 36% between 1999 and 2005 • 22% of kidneys transplanted in 2009 • DCD accounted for 13% of donors United States Organ Transplantation OPTN & SRTR Annual Data Report 2010 • UK • DCD kidneys in UK increased from 3% to 32% between 2000 and 2009 Summers DM, Johnson RJ, Allen J, et al. Analysis of factors that affect outcome after transplantation of kidneys donated after cardiac death in the UK: a cohort study. Lancet 2010
- 26. Machine Perfusion •Solutions • Eurocollins solution, UW solution, HTK solution, hyperosmolar citrate solution, Celsior solution, Institute Georges Lopez-1 solution • Hypothermic perfusion • Waters MOX DCM-100 • UP-100 • LifePort Kidney Transporter • Kidney assist • Normothermic perfusion • POPS system
- 27. Basic design ofa perfusion machine Waters MOX DCM-100
- 28. Hypothermic perfusion machine Normothermic perfusion machine
- 30. Cost effective? •LifePortKidney transporter • Cost savings = $86 750 per life-year gained • Cost utility ratio was minus $496 223 per quality-adjusted life-year (QALY) gained Cost-Effectiveness of Hypothermic Machine Preservation Versus Static Cold Storage in Renal Transplantation; H Groen; American journal of transplantation 2012
- 31. Not inferior oreven better? • No difference in primary non-function, acute rejection, long-term renal function or patient survival Systematic review and meta-analysis of hypothermic machine perfusion versus static cold storage of kidney allografts on transplant outcomes; J. M. O’Callaghan; Transplantation 2012 • Decreased rates of DGF To Pump or Not to Pump: A Comparison of Machine Perfusion vs Cold Storage for Deceased Donor Kidney Transplantation; Robert M Cannon; J Am Coll Surg 2013
- 32. Static Cold Storage vs Hypothermic Machine Perfusion
- 33. Study end points • Delayed graft function (DGF) • Requirement for dialysis during the first week after transplantation • Primary Non-Function (PNF) • Permanent lack of function of allograft from the time of transplantation • Graft survival/ failure • Censored at the time of death
- 34. SCS vs HMP • International randomized controlled trial with 336 donors
- 35. Results • Delayedgraft function • significantly reduced risk of DGF (adjusted odds ratio, 0.57, p=0.01) • Primary Non-Function • More than 2 times higher in SCS but not significant (4.8% vs 2.1%, p=0.08) • Graft survival/ failure • Three-year allograft survival superior in MP group (91% vs 87%, hazard ratio, 0.60 p=0.04)
- 36. ECD Subgroup analysis • Expanded criteria donors (94 out of 336) had a significant three-year graft survival (86% vs 76%; adjusted hazard ratio, 0.38; p=0.01) • Another RCT with 91 ECDs had similar results: • significantly reduced the risk of DGF (29.7% vs 22%, OR 0.460, P = 0.047). • incidence of nonfunction in the CS group (12%) was four times higher than in the MP group (3%) (P = 0.04). • One-year graft survival was significantly higher in machine perfused kidneys (92.3% vs. 80.2%, P = 0.02). Treckmann J, Moers C, Smits J, et al. Machine perfusion versus cold storage for preservation of kidneys from expanded criteria donors after brain death. Transpl Int
- 37. Donation after CirculatoryDeath (DCD) • Donors not declared brain death • Ethical concerns “Hypothermic machine perfusion was associated with a reduced risk of DGF and better early graft function up to 1 month after transplantation. Routine preservation of DCD kidneys by hypothermic machine perfusion is therefore advisable.”
- 38. Future of HMP • Renal resistance indexes to evaluate marginal organs Jochmans I, Moers C, Smits J, et al. The prognostic value of renal resistance during hypothermic machine perfusion of deceased donor kidneys. Am J Transplant 2011 • Biomarkers to predict delayed graft function Moers C, Varnav OC, van Heurn E, et al. The value of machine perfusion perfusate biomarkers for predicting kidney transplant outcome. Transplantation 2010 • Other methods: normothermic perfusion, oxygen persufflation Matsuno N, Konno O, Mejit A, et al. Application of machine perfusion preservation as a viability test for marginal kidney graft. Transplantation 2006
- 39. Take Home Messages • Only possible improvement in SCS is new solutions • HMP is the way to go? • Rapidly advancing field • Possible additional benefit of HMP in the future • Not inferior to SCS • Significant advantage for ECD • Look out for other developing methods • HMP in other organs?
- 40. Special Thanks Supervisor:Dr. G Leung Acknowledgement: Dr. MK Yiu
- 41.
- 42. Which one better? Primary end point = Delayed Graft Function (DGF)
- 43. Which one better? Lynch RJ, et al. AJT 2008; 8:567-73
- 44. Post-transplant kidney graftsurvival Living Donor: HTK n=475 UW n=475 Deceased donor: HTK n=317 UW n=317 Lynch RJ, et al. AJT 2008; 8:567-73
- 45. Lynch RJ, etal. AJT 2008; 8:567-73