IL TRAPIANTO

DA CUORE NON BATTENTETeresa Rampino

11 Settembre 2008….. 2018

I° TRAPIANTO NHBD

TRAPIANTI DA DONATORE A CUORE NON BATTENTE O DOPO MORTE CIRCOLATORIA ( DCD) in Italia

Dati CNT 2018 parziale

107 TX RENE

Pavia

Milano

Padova

Bologna

FirenzeSiena

Verona

Palermo

Un rene di serie B?

DCD DBD

Donor after Circulatory Death

Permanent absence of circulation and respiration

Criteria for determination of death

Cardiac Arrest Loss of perfusion

ISCHEMIA

ANOXIA

Anoxic Injury

Irre

vers

ible

Inju

ry

>5’

Patient death

25-75’

15-120’

15-33’

24 h tissues

DONOR IN ASYSTOLE

Trends in Anaesthesia and Critical Care (2013); 72-76

Maximum tolerable warm ischaemia time in

transplantation from non-heart-beating-donors

PERIODO “NO TOUCH”

IL PERIODO IMPOSTO DALLA LEGGE PER LA DICHIARAZIONE DELLA MORTE CARDIACA

20 min

COUNTRYNO-TOUCH TIME

(MINUTES)

AUSTRIA 10

BELGIUM 5

CZECH REPUBLIC 10

FRANCE 5

ITALY 20

LATVIA 15

THE NETHERLANDS 5

UNITED KINGDOM 5

SPAIN 5

SWITZERLAND 10

Wind et al. Crical Care 2013, 17:R217

Variability of DCD protocols in Europe

AUTORESUSCITATIONE

«Lazarus phenomenon»

Ritorno spontaneo alla circolazione non assistita dopo l’arresto cardiaco

Homby K, Homby L, Shemie SD Crit Care Med 2010 (38), 5

Dopo un perioido“no-touch” di 20 minuti non esiste la possibilità di autoresuscitazione

Nel contesto italiano

CoordinamentoProtocollo ben definitoEsperienzaRisorse tecniche adeguate

Modified Thuong M et al, Transplant International 2016; 29: 749–759

(1995)The Maastricht categories of NHBD

Uncontrolled

Controlled

Partiallycontrolled

ACC

Heart activity

DCD Donor DEATH

ECMO

ADVANCED RESUSCITATION PROGRAM

Neurological

criteria

Cardiac

criteria

ECMO prior to death (EPD)

Class UNCONTROLLED

I Dead on arrival

II Unsuccessful resuscitation

150 min

TOTAL WARM ISCHEMIA TIME

1 – 4 hs (max 6)

ACLS

DECLARATION OF DEATH

CPR

EC

G20 min15 -20m

No flow

CardiacArrest

Organ Preservationin situ

Harvesting

Transp

lant

Cold Storage / Machine Perfusion

Low flow

DCD - UNCONTROLLED

ACLS Advanced CardiovascularLife Support

CPR CardiopulmonaryResuscitation

Class CONTROLLED

III Awaiting cardiac death

IV Cardiac death in a brain-dead donor

TOTAL WARM ISCHEMIA TIME

1 – 4 hs (max 6)

DECLARATION

OF DEATH

EC

G

20 min

No flow

Asystole

Organ Preservation

Harvesting

Tra

nsp

lan

t

Cold Storage/

Machine Perfusion

Low flow

DCD - CONTROLLED

withdrawal life

sustaining

treatment

Blood Pressure

Agonal phase

Functional WIT

Category IICategory III

VS

DIFFERENCES IN ORGAN PERFUSION

CONTROLLED UNCONTROLLED

filmato

NORMOTERMIC REGIONAL PERFUSION

MACROSCOPIC

PERFUSION

MACHINE

HISTOLOGIC

KIDNEY EVALUATION CRITERIA

PRE -TRANSPLANT KIDNEY BIOPSY

ACUTE DAMAGE

CHRONIC DAMAGE

REMUZZI HISTOPATHOLOGICAL SCORE

CAPILLARY AND ARTERIOLAR TROMBOSIS

ACUTE DAMAGE

YES NO

TX

TUBULAR NECROSIS

DCD KIDNEY BIOPSY AT RETRIEVAL

RR 0,33

F 0,68 ml/min

DCD KIDNEY BIOPSY AFTER PULSATILE PERFUSION

Renal Resistance

(RR):

RR < 0,40

Perfusion Flow:

> 60 ml/min

Perfusional Criteria

RENAL RESISTENCE TREND DURING HYPOTHERMIC MACHINE PERFUSION IS PREDICTIVE OF GRAFT OUTCOME

RISORSE TECNOLOGICHE

PRESERVATION EX SITU

VS

HYPOTHERMIC

MACHINE PERFUSION

NORMOTHERMICSUBNORMOTHERMIC

4°C 20-25°C 32-36°C

+ O2 + O2

EX-VIVO MACHINE PERFUSION FOR KIDNEY PRESERVATION

Curr Opin Organ Transplant 2018, 23:369–374

Trapianto DCD: ne vale la pena?

Snoejis MG et al. JASN 2010

Kidneys from DCD provide survival benefit

Kidney International (2015)

Kidney donation after circulatory death (DCD) versus donation after brain death ( DBD)

Snoeijs MGJ et al. Transplantation 2010

Kidneys transplantation from DCD

DONOR IN ASYSTOLE

PRIMARY NON FUNCTION (PNF)perdita permanente della funzione del rene subito

dopo il Tx

PRIMARY NON FUNCTION (PNF)FREQUENCY ACCORDING TO TYPE OF DONATION

Rigetto iperacuto

CID

Sindrome Emolitica Uremica

Recidiva immediata di malattia di base

Ossaluria primaria

Trombosi

Emodinamica intraoperatoria

CAUSE PNF

Risk factors for primary non-functionin DCD

BMI > 25 kg/mq

Terminal creat.

Recipient age

Flow rate > 70

HLA mismatch

Resistive index > 0,4

Warm ischemia time>30 min

Donor category

Donor age>40y

Cause of death (CV)

Pre op sys BP<130 mmHg

Intra op sys BP<110mmHg

Central venous BP <4cmH2O

Post-operative graft functionAccording to average intra operative Central Venous Pressure

4

53 20

8 16

RENAL CORTICAL NECROSIS

TAC

ECOGRAFIA CON MDC

ISTOLOGIA

DELAYED GRAFT FUNCTION (DGF)Necessità di dialisi entro la prima settimana dopo

trapianto renale

DCD DBD ODDS p VALUE

DGF 72% 18% 10,3 < 0,001

DELAYED GRAFT FUNCTION in Kidney Transplantation From Donors After Cardiac Death

Transplantation, Volume 90, Number 10, November 27, 2010

0%

20%

40%

60%

80%

100%

DBD DCD

DG

F

Transplant International (2011) 676-686

ControlledDCD

UncontrolledDCD

DGF in Kidney Transplantation from controlledversus uncontrolled donation after circulatory death

Attivazione linfociti TDAMPs

Cellule dendriticheROS

Interleukines

DGF influenza la sopravvivenza di un trapianto da donatore a cuore non battente

Snoeijs et al..Transplantation • 90, 10-27, 2010

DCD GRAFT SURVIVAL

Delayed Graft FunctionImmediate Graft Function

Gra

ftsu

rviv

al

Time after transplantation (Yr)

Graft survival of DCD and DBD kidney with DGF

DCD with DGFDBD with DGF

DONATION AFTER BRAIN DEATH

DONATION AFTER CIRCULATORY DEATH

ischemia

Necrosi tubulare

acuta

Catecholaminestorm

Cytokines

Peripheralischemia

IL 1TNFIL 6

Vasoconstriction

Activation of endothelium

Immune response

MHC

Organinflammation

IL 1

TNF

IL 6

COMPLICATIONS AFTER DCD KIDNEY TRANSPLANTATION

PAVIADCD-EPD KIDNEY TRANSPLANTS

Modified Maastricht classification DCD

Number of transplanted

patients Sex of recipients

II 17 11 M 6F

III 6 4M 2F

IV 1 1M

ECMO prior to Death (EPD)

13 8M 5F

37

24 DCD 13 ecmo ECLS

0

2

4

6

8

10

20

08

20

09

20

10

20

11

20

12

20

13

20

14

20

15

20

16

20

17

20

18

*

Donor Age (years) ( mean and sd) DCD group 51± 8.3

Recipient Age (years) ( mean and sd) DCD group 53.8±11.2

Sex of donor M/F DCD group 20/3

Sex of recipient M/F DCD group 16/7

DEMOGRAPHIC CHARACTERISTICS

VARIABLE MEDIAN IQR

DAYS OF DGF 11.5 8.25-17.5

NUMBER OF

DIALYSIS

6 4--9

DCD Group

VARIABLE MEDIAN IQR

DAYS OF DGF 4 1-9.5

NUMBER OF DIALYSIS 2 0--5

EPD Group

DGF 53% DGF 90%

Delayed Graft Function

GRAFT SURVIVAL

87%

13%

graft survival

graft loss

Trombosi vena renalePNF

Sepsi severa

DCD EPD

92%

8%

graft survival

graft loss

PNF

PATIENT SURVIVAL

69%

31%

surviving patients

dead patients

DCD EPD

87%

13%

surviving patients

dead patients

CancroComplicanze cardiovascolari

CancroComplicanze cerebrovascolari

DBD w

eek 1

DCD w

eek 1

EPD w

eek 1

DBDye

ar 1

DCD y

ear 1

EPD yea

r 1

DBD yea

r 3

DCD y

ear 3

EPD yea

r 3

0

5

10

15

*

*p<0.001 vs DBD and EPD week 1

° °p<0.001 vs DBD, DCD, EPD year 1,3

se

rum

cre

atin

ine

mg

%

RENAL FUNCTION in DCD, EPD and DBD

Induction Immunosuppressive therapyPAVIA

Thymoglobuline

2017

2016

2015

2014

2013

2012

2011

Thymoglobuline[iperimmune/diabetic patients]

Basiliximab

+ steroid, CNI inhibitors and MMF

DGF; 85%

THYMOGLOBULINE

DGF 76%

PNF; 9%

BASILIXIMAB

DGF and PNF

9 days(Median)

11 days(Median)

IR 15% IR 15%

DCDDBDSTESSO PROGRAMMA VISITE FOLLOW UP

STESSE TERAPIA IMMUNOSOPPRESSIVA

STESSO PROGRAMMA BIOPSIE PROTOCOLLARI

THE FUTURE

Stem cellsPharmaco therapyAnti inflammatory reagentsGene transferOxygenation

Kidney conditioning with

Rampino T et al.

Rene umano

Un rene di serie B?

DCD DBD