Transplant of marginal/NHBD kidneys and outcomes: kidney David Talbot

The increasing use of NHBD kidneys

DBD and DCD kidney transplants by centre, 2008/2009 financial year

Kidney transplant outcomes for DBD/DCD donors Graft survival DCD DBD Patient survival

Standard and Expanded Criteria donors: Standard donor: donors 10-39yrs, no hypertension, no CVA, terminal serum creatinine< 133μmol/l Expanded donor: >60 or of the above (producing a relative risk >1.7) (Am J Trans 2002; 2:1. Transplantation 2002; 74:1281. Am J T 2003; 3:114. Ann Surg 2004; 239: 688.) Where does DCD/NHBD lie in relation ship to expanded versus standard donors?

UNOS data: 2562 DCD 62,800 Standard criteria(<50) 12,812 Expanded Criteria donor

Standard versus expanded versus DCD:

Unified donor retrieval teams from 1 st April with a desire to share NHBD kidneys (NHS BT) Unification means that there is a need for consensus: How long do we wait after withdrawal of support? Should we use an Apnoea score? Machine versus static cold storage? Is prolonged cold ischaemia safe for DCD/NHBD kidneys? Which kidneys can be shared?

How long to wait after withdrawal?

New England Organ bank: Oct 99-April kidneys 39 livers *Small numbers, best donors, short time between extubation and death but suggestion that primary function in kidneys better if hypotensive period is short: (confirmed with composite end points of the liver) though no difference to long term outcome for the kidney *NB Dominic Summers GFR DCD versus DBD equivalent though higher at 3/12

Newcastle team call outs in

Wisconsin Apnoea Score: Chapter 15 Donors without a heart beat in the US- Anthony D’Alessandro from Organ donation and transplantation after cardiac death (DT/ADA ISBN )

CriteriaAssigned pointsScore Spontaneous resps after 10mins Rate >12 Rate <12 TV>200cc TV<200cc NIF>20 NIF< No spontaneous resps9 BMI: < >303 No vasopressors1 Single vasopressors2 Multiple vasopressors3 Patient age: Endotracheal tube3 Tracheostomy1 Oxygenation after 10 mins>90% 80-89% <79% Final score/47

Wisconsin Apnoea score: 8-12: High risk of continuing to breathe after extubation Moderate risk for continuing to breathe after extubation Low risk for continuing to breathe after extubation 84.3% accurate of death within 2 hours Wisconsin sends a team if score >12

?Evaluate a UK score CriteriaAssigned pointsScore No spontaneous resps9 BMI: < >303 No vasopressors1 Single vasopressors2 Multiple vasopressors3 Patient age: CPAP?9 Endotracheal tube3 Tracheostomy1 Final score/40

Risk of continuing to breath on withdrawal High risk: Tracheostomy, no inotropes, young, thin, spontaneous breathing -4 Moderate risk: bmi 25-29, single inotrope,31-50 years of age, intubated, spontaneous breathing- 9 Low risk 1: High bmi, multiple inotropes, 51+, endotracheal tube, no spontaneous breathing- 21 Or Low risk: High BMI, 51+, no inotropes, CPAP- 16

Machine versus static storage Is machine perfusion with GST etc needed for viability assessment? Is machine perfusion better than static storage for marginal kidneys? Does machine perfusion confer some benefit when kidneys are exchanged?

Newcastle NHBD Donor numbers Maastricht IIMaastricht IIIMaastricht IV Donor number35222 Kidneys used31344 Proportion used44%79%100% Proportion kidney transplants of total 44.9%49.3%5.8%

Newcastle versus Bristol NHBD MIII- BTS 2007 Vijayanand collected data on MIII renal transplants : SCS=Bristol, HMP= Ncl

Bristol versus Newcastle

Others Oxford/Plym/New p = 0.39 (logrank) Dominic Summers NHS BT 2010 UK outcome machine versus cold. Units that ‘do’ versus units that don’t. Censoring out those involved in UK MPS/static storage

Machine Perfusion or Cold Storage in Deceased-Donor Kidney Transplantation Cyril Moers, Jacqueline M Smits, Mark-Hugo J Maathuis, Jurgen Treckmann, et al. The New England Journal of Medicine. Boston: Jan 1, Vol. 360, Iss. 1; pg. 7 The New England Journal of MedicineJan 1, 2009

The Blue kidney at retrieval: Ray et al NEJM April 2009; 360: kidneys from 19 donors usually femoral cannulation, Maastricht II or misplaced cannulae. Blue at explant despite flushing. Machine perfusion: kidneys improved 34 transplanted with reasonable outcomes- 10 dual, 14 single kidney transplants

Use/non use of kidneys from NHBD’s by unit: (highlighted units not using mps)

Units not using machine perfusion (April ) Total% Donors193 Kidneys retrieved 381 (total potential: ?386) 98.7% Kidneys used %

Use rate between machine perfusion sites (April ) OxfordPlymouthNewcTotal Donors Kidneys retrieved Kidneys used % used * *: Chi square versus other centres

Cold ischaemia after primary warm ischaemia Widely held that DCD organs extra- sensitive to damage by cold ischaemia Dominic Summers on NHS BT data of 748 DCD kidneys increased failure with: Old donors (>60 hazard ratio 2.3, p=0.001) Old recipients (>60 hazard ratio 2.03, p=0.01) Cold ischaemia (>12 hours hazards ratio 1.9 p=0.06)

% DGFNo crossmatch Crossmatchprobability DBD18%28%0.03 DCD54%52%NS Dominic Summers NHS BT data Suggests minimising cold ischaemia is critical Abstract number 0094

In summary DCD versus DBD kidneys same outcome survival/gfr of MIII donors Agonal period- how long- short for liver, kidney can be long (with DGF but no consequence on long term outcome) To minimise excessive call outs a form of ‘apnoea’ test could be employed by a national retrieval team

In summary-2 Machine perfusion for kidneys after NHBD not essential for MIII donors Outcome improved by MPS according to the European trial Non use rate of kidneys is higher with static storage of the order of 10% Cold ischaemia should be minimised for kidneys particularly NHBD

Sharing NHBD kidneys, which donor? which kidney? Meeting Standard donor: donors 10-39yrs, no hypertension, no CVA, terminal serum creatinine< 133μmol/l Short agonal period (short period whilst BP<60)- (max ?1 hour- same as liver) Short period asystolle to perfusion (max ?30mins) Aortic cannulation rather than femoral Kidney pale and well flushed on retrieval Experienced retrieval surgeon UW flush after initial low viscosity flush Marshals or HTK Machine perfusion would give some security to the receiving centre Transplant unit should not be too far from donor unit Recipient transplanted with a virtual crossmatch to minimise cold ischaemia

Non sharing of NHBD kidneys but national retrieval team: Meeting All other donors than standard: (older donors, hypertension, CVA, terminal serum creatinine> 133μmol/l) Longer agonal period permitted ?4/5 hours Short period asystolle to perfusion (max ?45mins) Aortic or femoral cannulation but aortic preferable Local judgement as to kidney use Machine perfusion or static according to local preference as local unit will be using them Minimise cold ischaemia ?virtual crossmatch

Immunosuppression post renal transplant after DCD Schadde et al Transplant Int 2008;21:625 campath v atg v Il2Rab- similar outcomes slightly higher infection with campath Sanchez-Fructuoso Trans Int 2005; 18: 596 best with antiIl2rAb, low dose tacr, mmf and steroids Wilson BJS :681 anti Il2r, mmf and pred with delayed tacr

Oxford/Plym/New Cold Oxford/Plym/New machperf Others Cold storage Others Mach perf n=18 p = 0.78 Kaplan-Meier of 5yr Graft survival (all-cause graft loss) Dominic Summers NHS BT 2010