Donation After Circulatory DeathLocal Transplant Outcomes

Dr. Jeff Zaltzman

Director Division Nephrology, Medical Director Diabetes Comprehensive Care Program, St. Michael’s Hospital

CMO Transplant, Trillium Gift of Life Network

Professor of Medicine , University of Toronto

Objectives

• DCD in Canada

• DCD impact on DBD

• Local transplant outcomes from DCD donors

Canada 2015: 651 deceased donors, 138 DCD(21%)Record year

Pop: 35,851,000RPM=18.1

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2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015

Canada 2001-2015

NDD DCD

Canadian DCD activity 2006-2015

PROVINCE TOTAL DCD 2006-2015 % of all DCD

CANADA 637 100

BC 64 10.0

ALBERTA* 24 3.8

SASK 1 0.15

MANITOBA* 0 0

ONTARIO 426 67

QUEBEC 99 15.5

NOVA SCOTIA 23 3.6

NEW BRUNSWICK 0 0

PEI 0 0

NFLD 0 0

* Both Calgary and Manitoba have begun DCD activity in 2016

Donation after circulatory death CD RPM 2006-2015 (courtesy of CBS)

Ontario Deceased Donation 2015 :269 DD, 84(31%) DCD, both records! 2016 will smash these #s, 295 DD (90 DCD) as of Oct 31 2016!!!!!

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DCD

NDD

Ontario: 13.5 millionDonor RPM=22 (2016 Expected Donor RPM~25)

Ontario DCD transplants June 1 2006-Sept 30 2016503 DCD donors

Organs Transplanted Organ Number

KIDNEY 850

LIVER 168

LUNG 135

PANCREAS (whole) 33

TOTAL 1186*

Has DCD impacted on DBD donors in Ontario?

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CVA/Stroke Head Trauma Anoxia Other

Pre (2002/03 - 2005-06) Post 1 (2006/07 - 2009/10)

Post 2 (2010/11 - 2013/14)

Cause of Death; all donors

3 Eras: Pre DCD, Post DCD 1(2006-2010), Post DCD2 (2010-2014)

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1,000

Pre (2002/03 - 2005-06) Post 1 (2006/07 - 2009/10) Post 2 (2010/11 - 2013/14)

NDD Donors DCD Donors All Donors

No reduction in Transplant activity since DCD

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Kidney Liver Lung Heart KP & P

Local transplant outcomes from DCD donors

Age 36 years (±15)

Gender 59 male (69%)

Brain Injury

32 trauma (37%)

24 stroke/bleed (28%)

28 anoxic injury (33%)

2 other (2%)

BMI 24 kg/m2 (±4)

WIT (from WDLS) 29 minutes (±17)

DCD Donor CharacteristicsLHSC and TGH Experience Courtesy Dr. R Hernandez

n = 91

Aims:

• Develop a definition of f-WIT based on hemodynamic parameters

• Primary Outcomes:

1) Graft Failure2) Biliary Complications

Methods:

• Multi-center (London and Toronto, Canada)

• July 2006- Sept 2013

• All recipients of Maastricht Category III DCD liver allografts

DCD Liver Graft Survival Rates

72.87%

62.91%

88.11%

78.16%

84.11%

58.77%

65.47%

79.43%

73.78%

83.26%

68.81%

77.04%

55%

60%

65%

70%

75%

80%

85%

90%

95%

100%

6 12 24 36MONTHS POST TRANSPLANT

GR

AF

T S

UR

VIV

AL R

AT

E

)15,644(SCD )903(DCD )4,910(ECD

Deceased Donor Liver Transplants Performed 1/04 – 6/07*

*Based on OPTN data as of March 7, 2008

Intrahepatic Cholangiopathy

• 33–50% incidence of IC

• High rate of graft failure and re-Tx

DCD Recipient CharacteristicsLHSC and TGH Experience

Age 54.5 years (±9)

Gender 74% male

Diagnosis Most common: HCV and Etoh

MELD (uncorrected) 21 (±7)

HCC 23 %

CIT 5.6 hours (±1.4)

DCD – ResultsLHSC and TGH Experience

Patient survival 83.0%

Graft survival 79.5%

PNF 4.0%

Re-LT 4.0%

Biliary complications 18%

Ischemic cholangiopathy 6.3%

Vascular complications 0%

n = 91 DCD-LT, Mean follow-up = 5 years

Graft Failure

OR p value

Donor Age 1.08 0.019

WIT 1.02 0.163

MAP <50mmHg 1.02 0.622

MAP <55mmHg 1.02 0.153

Systolic <55mmHg 1.01 0.863

• Univariate analysis• total warm ischemia time (WIT) • oxygen saturation• mean arterial pressure (MAP) • systolic pressure (sBP)

• Donor age was a significant predictor of outcome (p=0.019)• dichotomized at 55 years

none were

predictive of graft

failure

Age Graft Failure

<55 7%

>55 33%

Results: Graft Failure

Biliary Complications:

OR p value

Donor Age 1.02 0.258

WIT 1.02 0.134

MAP <50mmHg 1.1 0.013

MAP <55mmHg 1.1 0.017

Systolic <55mmHg 1.12 0.021

Systolic <50mmHg 1.14 0.02

Saturation <70% 1.02 0.285

Saturation <60% 1.02 0.345

OR of univariate analysis

Time Biliary Complications

<25 min 9%

>25 min 56%

Results: Biliary Complications

• MAP <50 mmHg

Primary Endpoints:

• Graft failure was observed in 4% of patients

• Biliary complications occurred in 24% of patients

Conclusions

• Donor age was the only good predictor of graft failure

• MAP <50mmHg was the best predictor of biliary complications• Relatively low risk when <25min

• Total WIT and oxygen saturation were not good predictors of failure or biliary complications

26 26

Toronto General: DCD vs. NDD Lung

Transplants Courtesy Dr. M. Cypel

1983-09/2016 (YTD)

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DCD

NDD

Total DCD performed to-date(N=135)

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DCD donors +/- EVLP2007- 09/2016 (YTD)

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43

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3 401

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EVLP (+)

EVLP (-)

N for DCD-Tx to-date =135DCD-EVLP-Tx= 91/135 (67.4%)

2011

• DCD donors / All deceased donors= 42/220 (19%)

• DCD LungTx / All Lung Tx= 16/102 (16%)

• DCD Lung Tx / All DCD donors(utilization)= 15/42 (38%)

475 Lung TxJan 07-Dec 11

432 BDD Transplants

BDD Group N= (413)

19 ECLS bridge to Tx(excluded)

3 ECLS bridge to Tx(excluded)

DCD group (n=40)

43 DCD Transplants

Outcomes of DCD vs BDDVariable DCD

(N=40)

BDD

(N=413)

P Value

PGD 3 at ICU arrival (%) 27.5 17 0.12

PGD 3 at 72h (%) 12.5 10 0.62

ECMO (%) 5 2.7 0.12

Mechanical ventilation ( median days) 2.2 2.7 0.78

ICU stay (median days) 4 4 0.69

Hospital stay (median days) 22 22 0.58

30 Mortality (%) 5 4 0.10

Survival

0 365 730 1095 1460 18250

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100BDD

DCD

p= 0.48

87%

71%

55%

Days after transplantation

Perc

en

t su

rviv

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Ontario DCD kidneys

• By Sept 30, 2016, 850 kidney transplants from DCD donors in Ontario

• Most kidneys (all types) are placed on pulsatile perfusion pumps

• In 2016, decision by kidney working group to increase age of acceptance of DCD kidneys from 65 to 70 ( 80 for NDD)

Definition of Extended criteria donor (ECD):

1) any donor 60 yrs or older

2) donor 50-59 with 2/3 of following: a) hypertension, b) ICH,

c) terminal sCr 132 umol/l

December 2014: USA went to new KAS, using Kidney Donor RiskKDRI or KDPI and recipient risk

St. Michael’s Hospital data Recent Era of DCD : 2012-2016

• Reported on 3 year Ontario outcomes 2006-2009 Organ donation after cardiac death: donor and recipient outcomes after the first three years of the Ontario experience. Hernandez et al. Can J anaesth 2011 58(7):599

• DCD and and NDD were equal

• DCD/ECD worse renal function.

• Early DCD were highly selected.

• In more recent era of DCD, donors are sicker older. More anoxic brain injury

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CVA/Stroke Head Trauma Anoxia Other

Pre (2002/03 - 2005-06)Post 1 (2006/07 - 2009/10)Post 2 (2010/11 - 2013/14)

Cause of Death; all donors, Ontario

DCD patient and Kidney graft survival: 2006-2009

• 1 year patient survival- 96%

• 1 year death censored allograft survival-97%

• 1 year graft survival- 92%

• Patient deaths : 1 CVA, 1 MVA, 1 lymphoma, 1 mesothelioma, 1 progressive neurologic

• Graft losses: 2 venous thrombosis, 1 recurrent GN

Organ donation after cardiac death: donor and recipient outcomes after the first three years of the Ontario experience. Hernandez et al. Can J anaesth 2011 58(7):599

Other Kidney DCD outcomes

• DGF ( need for dialysis) – 67%

• Use of ALG induction- 90%

• Mean WIT – 42 ± 13 min

• Mean CIT - 8.3 ± 3.8 hr

• Use of pumps - 34%

• ECD/DCD - 20/126 (16%)

Renal Function DCDSDC vs ECD

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Dy3 Dy7 Mth1 Mth3 Mth6 Mth12

SDC

ECD

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age creatinine Hgb ACR

St. Mikes living/deceased donor recipients 2012-2016

LD=189, DD=445

LD DD

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age creatinine Hgb ACR

Deceased Donor typesRecipient outcomes

2012-2016

NDD SCD NDD ECD DCD SCD DCD ECD

N= 169 119 89 29

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NDD SCD NDD ECD DCD SCD DCD ECD

Allograft Survival by donor type

1 year 3 year

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NDD SCD NDD ECD DCD SCD DCD ECD

Death-censored graft survival by donor type

1 year 3 year

%

Summary

• DCD is fastest growing source of deceased donors in Canada

• Canada DCD rates now exceed USA

• No evidence that DCD impacts DBD donor rates

• Ontario has largest % DCD donors in all North American jurisdictions

• Transplant outcomes with lungs appear comparable with NDD

• Liver outcomes less favourable, but donor age and MAP pre death time play a role

• Kidney allografts slightly inferior, but differences diminish when death censored graft loss is accounted for