Transplant of marginal/NHBD kidneys and outcomes: kidney

David Talbot

The increasing use of NHBD kidneys

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Transplant Centre

Num

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DBD DCD

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

Kidney transplant outcomes for DBD/DCD donors

Graft survival

% g

raft

surv

ival

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years post-transplant0 1 2 3 4 5

% p

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years post-transplant0 1 2 3 4 5

DCDDBD

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 50-60 + 2 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 1st 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 06143 kidneys39 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

Team attending and death notoccuring 2004-6

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25

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75

Total No.attending No Death

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ber

Newcastle team call outs in 2004-6

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 978-0-19-921733-5)

Criteria Assigned points Score

Spontaneous resps after 10minsRate >12Rate <12TV>200ccTV<200ccNIF>20NIF<20

131313

No spontaneous resps 9

BMI: <25 1

25-29 2

>30 3

No vasopressors 1

Single vasopressors 2

Multiple vasopressors 3

Patient age: 0-30 1

31-50 2

51+ 3

Endotracheal tube 3

Tracheostomy 1

Oxygenation after 10 mins>90%80-89%<79%

123

Final score /47

Wisconsin Apnoea score:

• 8-12: High risk of continuing to breathe after extubation

• 13-18 Moderate risk for continuing to breathe after extubation

• 19-24 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

Criteria Assigned points Score

No spontaneous resps 9

BMI: <25 1

25-29 2

>30 3

No vasopressors 1

Single vasopressors 2

Multiple vasopressors 3

Patient age: 0-30 1

31-50 2

51+ 3

CPAP ?9

Endotracheal tube 3

Tracheostomy 1

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 1999-2002

Maastricht II Maastricht III Maastricht IV

Donor number 35 22 2

Kidneys used 31 34 4

Proportion used 44% 79% 100%

Proportion kidney transplants of total

44.9% 49.3% 5.8%

Newcastle versus Bristol NHBD MIII- BTS 2007

Donor Age

HMP SCS

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Primary Warm Ischaemic Time

HMP SCS

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Donor eGFR

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3m2

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• Vijayanand collected data on MIII renal transplants 2002-6: SCS=Bristol, HMP= Ncl

Recipient Age

HMP SCS

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Bristol versus Newcastle

PNF DGF

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HMPSCS

Perc

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Cold Ischaemic Time

HMP SCS

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eGFR

3 mon

HMP

3 mon

SCS

1 Yr H

MP

1 Yr S

CS

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60eG

FR m

L/m

in/1

.73m

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(Mea

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SD)

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, 2009. Vol. 360, Iss. 1; pg. 7

The Blue kidney at retrieval:Ray et al NEJM April 2009; 360:1460

• 38 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)

Table 3.4 Kidney donation and retrieval rates for non-heartbeating donors in the UK, 1 April 2008 - 31 March 2009, by centre/region Centre/region Non-heartbeating

kidney donors (pmp) Kidneys retrieved

(pmp) Kidneys used

(%)

Birmingham 18 (4.0) 36 (7.9) 29 (81) Bristol 13 (6.5) 26 (12.9) 22 (85) Cambridge 45 (17.6) 90 (35.2) 73 (81) Cardiff 7 (3.1) 14 (6.1) 14 (100) Coventry 2 (2.4) 4 (4.8) 2 (50) Edinburgh 11 (4.6) 20 (8.3) 17 (85) Glasgow 10 (3.7) 20 (7.5) 18 (90) Leeds 22 (5.8) 44 (11.6) 44 (100) Leicester 2 (0.9) 4 (1.8) 4 (100) Liverpool 8 (2.4) 14 (4.2) 14 (100) Manchester 12 (3.0) 23 (5.7) 22 (96) Newcastle 11 (3.8) 22 (7.6) 21 (95) North Thames 33 (4.4) 65 (8.7) 52 (80) Nottingham 3 (2.1) 6 (4.3) 6 (100) Oxford 14 (4.6) 28 (9.1) 27 (96) Plymouth 31 (17.0) 62 (34.1) 57 (92) Portsmouth 9 (3.7) 18 (7.4) 16 (89) Sheffield 4 (2.1) 8 (4.3) 7 (88) South Thames 20 (2.9) 40 (5.8) 32 (80)

TOTAL 275 (4.6) 544 (9.0) 477 (88)

Units not using machine perfusion (April 2008-2009)

Total %

Donors 193

Kidneys retrieved

381 (total potential: ?386)

98.7%

Kidneys used

321 83.2%

Use rate between machine perfusion sites (April 2008-9)

Oxford Plymouth Newc Total

Donors 14 31 11 56

Kidneys retrieved

28 62 22 112

Kidneys used

27 57 21 105

% used 96 92 95 93.8*

*: 0.0099 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)

% DGF No crossmatch

Crossmatch probability

DBD 18% 28% 0.03

DCD 54% 52% NS

Dominic Summers NHS BT data Suggests minimising cold ischaemia is criticalAbstract 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 27.4.10

• 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 27.4.10• 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 2005 92:681 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