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TRANSCRIPT
8/07/2014
1
CCCN 2014
Renal transplantation
28/06/2014
Patrick Peeters, M.D.
Ghent University Hospital, Belgium
Plan of presentation
1. Indications.
2. Contra-indications.
3. Allocation and donor aspects.
4. Patient work-up.
Casus: ♀ ° 1965
- ATCD:
‣ 1991 Abruptio placentae
‧ Hypovolemic shok -> AKI
‧ Polytransfusion +++ : 50 units PC
‣ 2008 CKD stage 5 -> pretransplant evaluation
‧ antiHLA class 1 : strongly positive
‧ AntiHLA class 2 : strongly positive
‧ vPRA 99.8%
‧ -> Eurotransplant Acceptable Mismatch program
‣ 2009 CKD stage 5d -> start HD
Patrick Peeters, M.D. – Dept Nephrology Ghent University Hospital, Belgium
8/07/2014
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Patrick Peeters, M.D. – Dept Nephrology Ghent University Hospital, Belgium
1/ Kidney transplant indications.
Patrick Peeters, M.D. – Dept Nephrology Ghent University Hospital, Belgium
Integrated ESRD Care
Residual
Renal
Function
Hemodialysis Cre
atinin
e C
leara
nce
(ml/m
in)
20
15
10
5
0
Time on
Dialysis Initiation of Dialysis
Transplantation
Peritoneal Dialysis
Transplantation
PD
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Why organ transplantation?
Organ transplantation is
Most effective
Life-saving
Cost-effective
Patient survival
Wolfe NEJM 1999; Meier-Kriesche Transplantation 2002
Patient survival
Wolfe NEJM 1999
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Graft outcome living versus deceased donor
transplantation
Terasaki P et al. N Engl J Med 1995;333: 333-336
Quality of life
-93% of the patients consider Tx as a new life and
a curative option
-90% have an increased quality of life
-> 75% can play an active role at home and carry
out housekeeping.
-45% go working again as before.
Total cost for all patients
.00 1.00 2.00
PERIOD
0
20000
40000
60000
80000
M ean TO TG LO B
8776
46036 43619
22150
78422
68592
24356
12810
4892
TYPE
PD HD Tx
Type:
0 = PD
1 = HD
2 = TX
Period:
0 = 1th hospital
1 = Year 1
2 = Year X
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Guideline 1.1 – Tx : Access to renal
transplantation UK 2011
We recommend that kidney transplantation should
be the renal replacement therapy of choice for
patients with chronic kidney disease stage 5 who
are considered fit for major surgery and for
chronic immunosuppression. All patients predicted
to have an increased life expectancy post-
transplantation should be assessed for
transplantation. Placement on the transplant
waiting list will be limited by individual co-
morbidity and prognosis. (1A)
Patrick Peeters, M.D. – Dept Nephrology Ghent University Hospital, Belgium
Guideline 1.2 – Tx : Access to renal
transplantation UK 2011
We recommend that living donor transplantation
should be considered the treatment of choice for
all patients suitable for renal transplantation when
there is an appropriate donor. (1A)
Patrick Peeters, M.D. – Dept Nephrology Ghent University Hospital, Belgium
8/07/2014
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6–12 months 12–24 months >24 months
Pre-emptive
Living donor graft survival
Duration of
pretransplant
dialysis
<6 months
Ev
en
t-fr
ee s
urv
ival
(%)
Months post-transplant
100
80
60
40
20
0 0 12 24 36 48 60 72 84 96 108 120
Meier-Kriesche HU, et al. Transplantation 2002;74:1377– 81
Pre-emptive
<6
12
24
>24 0
20
40
60
80
100
0
20
40
60
80
100
Living
29 Cadaveric
94
Meier-Kriesche HU, et al. Transplantation 2002;74:1377– 81
Annual adjusted graft loss
rates per 1,000 patients
Annual adjusted graft loss
rates per 1,000 patients
Guideline 1.3 – Tx : Access to renal
transplantation UK 2011
We recommend that patients with progressive
deterioration in renal function suitable for
transplantation should be placed on the national
transplant list within six months of their anticipated
dialysis start date. Pre-emptive transplantation
should be the treatment of choice for all suitable
patients whenever a living donor is available. (1A)
Patrick Peeters, M.D. – Dept Nephrology Ghent University Hospital, Belgium
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Guideline 1.4 – Tx : Access to renal
transplantation UK 2011
We recommend that there must be demonstrable
equity of access to deceased donor kidney
transplantation irrespective of gender, ethnicity or
district of residence. (1A)
Patrick Peeters, M.D. – Dept Nephrology Ghent University Hospital, Belgium
Guideline 1.5 – Tx : Access to renal
transplantation UK 2011
We recommend that age is not a contra-indication
to transplantation but age related co-morbidity is
an important limiting factor. (1B)
Patrick Peeters, M.D. – Dept Nephrology Ghent University Hospital, Belgium
Guideline 1.6 – Tx : Access to renal
transplantation UK 2011
We recommend that all transplant units should
have written criteria for acceptance on to the
waiting list. The benefits and potential risks
associated with transplantation should be fully
explained both verbally and in writing. Potential
transplant recipients should be informed of all
donor options including living related and
unrelated donation. (1C)
Patrick Peeters, M.D. – Dept Nephrology Ghent University Hospital, Belgium
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Guideline 1.7 – Tx : Access to renal
transplantation UK 2011
We recommend that all CKD 5 patients and CKD
4 patients with progressive disease should have
their suitability for transplantation assessed
annually and that appropriate patients should be
referred to a transplant centre. When
transplantation is considered inappropriate the
reason(s) should be documented. Patients should
be placed on, or removed from the waiting list only
after discussion and agreement with the
nephrologist, transplant surgeon and the patients
themselves according to local practice. (1C)
Patrick Peeters, M.D. – Dept Nephrology Ghent University Hospital, Belgium
Guideline 1.8 – Tx : Access to renal
transplantation UK 2011
We recommend that the care of the renal
transplant recipient is best undertaken by a multi-
disciplinary team. (1C)
Patrick Peeters, M.D. – Dept Nephrology Ghent University Hospital, Belgium
Guideline 1.9 – Tx : Access to renal
transplantation UK 2011
We recommend that simultaneous kidney-
pancreas transplantation or living donor renal
transplantation is the treatment of choice for
patients with Type 1 diabetes mellitus who are
suitable for renal transplantation. (1B)
Patrick Peeters, M.D. – Dept Nephrology Ghent University Hospital, Belgium
8/07/2014
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2/ Kidney transplant contra-indications.
Patrick Peeters, M.D. – Dept Nephrology Ghent University Hospital, Belgium
Cancer – ERBP 2013
Patrick Peeters, M.D. – Dept Nephrology Ghent University Hospital, Belgium
Cancer – ERBP 2013
Patrick Peeters, M.D. – Dept Nephrology Ghent University Hospital, Belgium
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C2H5OH - ERBP 2013
Patrick Peeters, M.D. – Dept Nephrology Ghent University Hospital, Belgium
HIV – ERBP 2013
Patrick Peeters, M.D. – Dept Nephrology Ghent University Hospital, Belgium
aHUS – ERBP 2013
Patrick Peeters, M.D. – Dept Nephrology Ghent University Hospital, Belgium
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The paradox of transplantation
UNDER-
IMMUNOSUPPRESSION
COMPLICATIONS REJECTION
OVER-
IMMUNOSUPPRESSION
The AXIS of EVIL - GW Bush
•Cardiovascular disease
•Infection
•Cancer
P Peeters, M.D. – Dept Nephrology - Ghent University Hospital, B
27 01 2011 Kuwait
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Mortality following kidney transplantion
Infection
Malignancy
Other
Cardiovascular
Cerebrovascular
20%
13%
7%
37%
23%
Patrick Peeters, M.D. – Dept Nephrology Ghent University Hospital, Belgium
Factors affecting the net state of
immunosuppression in transplant recipients
Patrick Peeters, M.D. – Dept Nephrology Ghent University Hospital, Belgium
Rubin
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Retrospective analysis of ANZDATA between 1980 and 2007
CVD is a leading cause of death with
a functioning graft
De
ath
ra
te
(pe
r 1
00
pa
tie
nt-
ye
ars
) 1,7
0,60,7 0,7
1,8
0,60,5
0,4
1,2
0,7
0,4 0,4
1,1
0,7
0,40,3
1
0,8
0,4 0,4
0,9
0,7
0,3 0,3
0,0
0,2
0,4
0,6
0,8
1,0
1,2
1,4
1,6
1,8
2,0
Cardiovascular Malignancy Infection Other
1980–1984
1985–1989
1990–1994
1995–1999
2000–2004
2005–2006
CVD, cardiovascular disease Pilmore HL et al. Transplantation 2010;89:851–7
Patrick Peeters, M.D. – Dept Nephrology Ghent University Hospital, Belgium
Cardiovascular risk factors in transplant
recipients
Diabetes
Hypertension
Dyslipidaemia
Smoking
Vascular disease
Pre-transplant
– low GFR
– proteinuria
– phosphate,
calcium, PTH
– LVH, arterial
stiffness
– anaemia
● NODAT
● Hypertension
● Dyslipidaemia
● Smoking
● Increased age
Post-transplant
– low GFR
– proteinuria
– LVH
– Anaemia
– Inflammation
GFR, glomerular filtration rate; PTH, parathyroid hormone;
LVH, left ventricular hypertrophy; NODAT, new-onset diabetes after transplantation
Rigatto C et al. J Am Soc Nephrol 2003;14:462–8;
Ojo AO. Transplantation 2006;82:603–11
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Eve
nts
(%
)
Holdaas H et al. Nephrol Dial Transplant 2005;20:974–80
Impact of statin usage: ALERT trial
Cardiac death and non-fatal AMI to 5 years
p=0.002
0
1
2
3
4
5
6
7
8
9
10
Time after randomisation (years)
Placebo
Fluvastatin
1 2 3 4 5
56%
0
512
503
502
483
487
466
468
449
417
417
522
521
No. of patients at risk
Fluvastatin
Placebo AMI, acute myocardial infarction
Post-hoc analysis of 2102 renal transplant recipients with total cholesterol
levels of 4-9 mmol/L randomised to receive either fluvastatin or placebo
Presence of LVH is a strong determinant
of risk of cardiovascular disease
LVH is detected in 74% of patients at start of dialysis1
LVH in the 5th year post-transplant predicted death (RR 2.15)2
Pa
tie
nt
su
rviv
al
(%)
1. Parfrey PS et al. Nephrol Dial Transplant 1996;11:1277–85;
2. Rigatto C et al. J Am Soc Nephrol 2003;14:462–8
p=0.02
0
20
40
60
80
100
0 10 20 30
No LVH in 5th year (n=236)
LVH in 5th year (n=38)
Time post-transplant (years)
LVH, left ventricular hypertrophy; RR, relative risk
Retrospective cohort study of LVH in renal transplant recipients
P Peeters, M.D. – Dept Nephrology - Ghent University Hospital, B
26 01 2011 Kuwait
Relative tumor risk after renal
transplantation
Cancer risk Cancer site RR
Small
(RR > 2)
Lung
Bladder, urothel.
Sarcoma
Liver
CNS
Melanoma
Cervix, vulva,vagina
2.67
2.81
3.38
3.96
3.99
4.13
4.42
Intermediate
(RR > 5)
Thyroid
Multiple myeloma
PTLD (vs. NHL)
Farynx, larynx
5.09
7.33
8.50
12.85
High
(RR > 15)
Kidney
Skin (non-melanotic)
Kaposi sarcoma
17.60
52.70
142.32
All malignancy
RR = 4.3
Adapted from Wimmer CD et al, Kidney Int 2007; 71: 1271
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P Peeters, M.D. – Dept Nephrology - Ghent University Hospital, B
26 01 2011 Kuwait
Risk factors associated with post-transplant
malignancy
Increasing age1,2
Exposure to UV light1
Previous exposure to carcinogens1
Genetic predisposition1,2
History of malignancy1
Cigarette smoking2
Analgesic abuse2
Immunosuppressive regimen,
eg CsA3 or tacrolimus6
Chronic viral infection2
Previous treatment with cytotoxic
agents, e.g. cyclophosphamide2
Transmission of malignancy
from donor2
Levels of immune system
components, eg high regulatory T-cells4
MMP-26 and MMP-9 levels5
Time after transplant6
Duration of haemodialysis6
Race6
Age at time of transplant6
1. Valantine H. J Heart Lung Transplant 2007;26:557–64;
2. Morath C et al. J Am Soc Nephrol 2004;15:1582–8; 3. Hojo M et al. Nature 1999;397:530–4;
4. Carroll RP et al. J Am Soc Nephrol 2010;21:713–22;
5. Kuivanen T et al. J Cutan Pathol 2009;36:929–36; 6. Imao T et al. Cancer 2007;109:2109–15
UV, ultraviolet; CsA, cyclosporin;
MMP, matrix metalloproteinase
43
Conventional Transplant specific
3/ Kidney transplantation
- allocation.
- donor aspects.
Patrick Peeters, M.D. – Dept Nephrology Ghent University Hospital, Belgium
Transplant Newsletter 2008 – Council of Europe
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Transplant Newsletter 2008 – Council of Europe
Patrick Peeters, M.D. – Dept Nephrology Ghent University Hospital, Belgium
Eurotransplant: donation,
waiting lists and transplants
Bron: ET Jaarverslag 2012
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Number of deceased donors in
Eurotransplant, used for a transplant
Bron: ET Jaarverslag 2012
Number of deceased donors used for
transplant, per million population
Bron: ET Jaarverslag 2012
Median age of deceased donors in
Eurotransplant, used for a transplant
Bron: ET Jaarverslag 2012
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Median age of patients on active waiting
list at year end
Bron: ET Jaarverslag 2012
Median waiting time for patients on
active waiting list at year end
Bron: ET Jaarverslag 2012
Median age of transplant recipients
(deceased donor transplants)
Bron: ET Jaarverslag 2012
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Median waiting time to transplant
(deceased donor transplants)
Bron: ET Jaarverslag 2012
Kidney waiting list, percentage of
patients at year end, by urgency
Bron: ET Jaarverslag 2012
Number of deceased donor kidney transplants, by
recipient urgency at transplant
Bron: ET Jaarverslag 2012
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Dynamics of the Eurotransplant kidney transplant
waiting list and transplants
Bron: ET Jaarverslag 2012
Dynamics of the Eurotransplant pancreas+kidney and islet+kidney
waiting list, pancreas+kidney, islet+kidney, pancreas and islet-only
transplants
Bron: ET Jaarverslag 2012
Eurotransplant Statistics 2013
Registrations on the kidney waiting list
Per country, 2012/2013 (compared to 2009-2011)
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Eurotransplant Statistics 2013
Reason for kidney exchange with other ET countries
Eurotransplant, Jan 2008 – Sept 2013
Eurotransplant Statistics 2013
Impact of kidney organ exchange on
selected patient groups
Belgium, 01.01.2001 - 31.12.2005
Evolution of the donor offers
Convertieratio UZG : 64,1 %
0
10
20
30
40
50
60
70
80
90
100
2004 2005 2006 2007 2008 2009 2010 2011 2012 2013
Donor Potentiëel Donor Effectief
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Donor refusal
Overlijdensoorzaak donoren
0%
20%
40%
60%
80%
100%
2004 2005 2006 2007 2008 2009 2010 2011 2012 2013
SHT na VKO Ander SHT CVA Anoxie / ander
Reason of donor death
Vascular Pancreas donor: 49 y
Heart donor: 63 y
Lung donor: 73 y
Kidney donor: 75 y
Liver donor: 90 y
Belgium: Oldest Organ donors 2013
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DCD - NON HEART BEATING DONOREN
donoren DCD ; België 2013 : 21,2 % .
2004 2005 2006 2007 2008 2009 2010 2011 2012 2013
% NHBD 0 3,6 19,1 16,3 4,8 15,8 12,5 12,3 11,4 14
% HBD 100 96,4 80,9 83,7 95,2 84,2 87,5 87,7 88,6 86
0,0
5,0
10,0
15,0
20,0
25,0
2004 2005 2006 2007 2008 2009 2010 2011 2012 2013
%
% DCD België % DCD UZ Gent
ECD score
Age O I
Screat O I
Hypertension O I
CVA O I
YES /NO
Improved Scoring System to
Assess Adult Donors For
Cadaver Renal Transplantation
Scott L. Nyberg
American Journal of Transplantation 2003: 715–72
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Table 2. Association between donor variables and recipient
creatinine clearance at 6 months
Donor variable
p-value by
univariate
analysis
p-value by
multivariate
analysis
Delta R21
1.1 Improvement in R2 by adding donor variable to linear regression
model.
Age < 0.001 < 0.001 0.0950
Creatinine
clearance < 0.001 < 0.001 0.0044
History of
hypertension < 0.001 < 0.001 0.0027
HLA mismatch < 0.001 < 0.001 0.0019
Cause of death < 0.001 < 0.001 0.0013
Duration of cold
ischemia < 0.001 < 0.001 0.0009
Ethnicity < 0.001 < 0.001 0.0003
CMV antibody
status < 0.001 0.019 0.0002
History of
diabetes
mellitus
< 0.001 0.022 0.0001
Improved Scoring System to Assess Adult Donors For Cadaver Renal Transplantation
American Journal of Transplantation
Volume 3, Issue 6, pages 715-721, 28 MAY 2003 DOI: 10.1034/j.1600-6143.2003.00111.x
http://onlinelibrary.wiley.com/doi/10.1034/j.1600-6143.2003.00111.x/full#f3
Improved Scoring System to Assess Adult Donors For Cadaver Renal Transplantation
American Journal of Transplantation
Volume 3, Issue 6, pages 715-721, 28 MAY 2003 DOI: 10.1034/j.1600-6143.2003.00111.x
http://onlinelibrary.wiley.com/doi/10.1034/j.1600-6143.2003.00111.x/full#f1
8/07/2014
25
Improved Scoring System to Assess Adult Donors For Cadaver Renal Transplantation
American Journal of Transplantation
Volume 3, Issue 6, pages 715-721, 28 MAY 2003 DOI: 10.1034/j.1600-6143.2003.00111.x
http://onlinelibrary.wiley.com/doi/10.1034/j.1600-6143.2003.00111.x/full#f2
Table 3. System for scoring adult donors in cadaver renal
transplantation
Variable Score
•CVA = cerebrovascular accident, including ischemic and
hemorrhagic types.
•1 To convert values to mL/s, multiply by 0.01667.
Age, y
< 30 0
30–39 5
40–49 10
50–59 15
60–69 20
≥ 70 25
History of hypertension
None 0
Yes; duration unknown 2
≤ 5 y 2
6–10 y 3
> 10 y 4
Creatinine clearance, mL/min1
≥ 100 0
75–99 2
50–74 3
< 50 4
HLA mismatch, no. of antigens
0 0
1–2 1
3–4 2
5–6 3
Cause of death
Non-CVA 0
CVA 3
Total points, range 0–39
Table 4. Renal function in 32 901 patients 12 months after cadaver
renal transplantation
Kidney Patient
s,
Mean
CrCl,
Patients with renal function2, no.
(%)
grade Points no. mL/mi
n1
Excell
ent Good Fair Poor
•2 Based on CrCl, mL/min; excellent, > 60; good, 40–60; fair, 20–
40; poor, < 20.
A 0–9 12 683 61.0 6 575 3 734 1 258 1 116
(52) (29) (10) (9)
B 10–19 11 005 51.8 3 931 3 950 1 691 1 433
(36) (36) (15) (13)
C 20–29 8 065 42.6 1 605 2 925 2 041 1 494
(20) (36) (25) (19)
D 30–39 1 148 33.7 95 337 404 312
(8) (29) (35) (27)
Table 4. Renal function in 32 901 patients 12 months after cadaver renal transplantation
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Improved Scoring System to Assess Adult Donors For Cadaver Renal Transplantation
American Journal of Transplantation
Volume 3, Issue 6, pages 715-721, 28 MAY 2003 DOI: 10.1034/j.1600-6143.2003.00111.x
http://onlinelibrary.wiley.com/doi/10.1034/j.1600-6143.2003.00111.x/full#f6
Rao (Kidney Donor Risk Index)
Transplantation 2009: 231-6
KDRI includes 14 donor and transplant factors, each found to be independently associated with graft failure or death:
donor age,
race,
history of hypertension,
history of diabetes,
serum creatinine,
cerebrovascular cause of death,
height,
weight,
donation after cardiac death,
hepatitis C virus status,
human leukocyte antigen-B + DR mismatch,
cold ischemia time
double or en bloc transplant
highest KDRI quintile (>1.45) had an
adjusted 5-year graft survival of 63%,
compared with 82% and 79% in the two
lowest KDRI quintiles (<0.79 and 0.79-
<0.96)
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Donor risk grade
Schold et al.
Am J Transplant 2005:757-65.
Adjusted parameter estimates for calculation
of risk score
Donor/Recipient CMV match D+/R−
Donor race African American
Donor age
Cause of death
HLA-A mismatches
Cold ischemia time1
Donor history of hypertension
Donor history of diabetes
Table 2. Donor grade statistics
Donor grade
Relative
frequency n
(%)
Risk score
range
AHRs1 0–1
years
AHRs1 1–5
years
1.195% CI for AHRs in parentheses.
I 5084 (11.1%) [0–0.234] Reference Reference
II 14881
(32.5%)
(0.234–
0.524]
1.34 (1.18,
1.53)
1.05 (0.94–
1.18)
III 15782
(34.4%)
(0.524–
0.853]
1.85 (1.63,
2.10)
1.36 (1.27–
1.51)
IV 7782
(17.0%) (0.853–1.17]
2.55 (2.24,
2.90)
2.00 (1.79–
2.24)
V 2321 (5.1%) >1.17 3.72 (3.22,
4.31)
2.22 (1.92–
2.57)
Table 2. Donor grade statistics
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The Broad Spectrum of Quality in Deceased Donor Kidneys
American Journal of Transplantation
Volume 5, Issue 4, pages 757-765, 27 JAN 2005 DOI: 10.1111/j.1600-6143.2005.00770.x
http://onlinelibrary.wiley.com/doi/10.1111/j.1600-6143.2005.00770.x/full#f4
DGF scores
delayed graft function (DGF) Nomogram
Irish et al.
J Am Soc Nephrol 2003: 2967
Neural networking
Walsh et al.
Histopathology scores
Anglicheau AJT 2008 :2325-34
Remuzzi NEJM
CADI
….
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Interpretatie van de “gap”
Patrick Peeters, M.D. – Dept Nephrology Ghent University Hospital, Belgium
Levende donor organen
Wachtlijst
Nieuw
Overlijden
NT
Allocatie
Match Transplantatie
Infrastructuur
0
10
20
30
40
50
60
70
80
90
100
0 1 2 3 4 5 6 7 8 9 10
jaren na transplantatie
%
overleving
Lever
Hart
Nier
??
Levende donor organen
“rechtvaardige orgaan allocatie”
THEORIE
- principes of biomedische ethiek : Beauchamp & Childress
* positieve bijdrage (beneficence)
* geen schade berokkenen (nonmaleficence)
* eerlijk (justice)
* autonomie patiënt (respect for autonomy)
=> in concreto : medical utility
equality of opportunity justice
Patrick Peeters, M.D. – Dept Nephrology Ghent University Hospital, Belgium
Organ allocation within Eurotransplant
1. Immunologic compatibility : AB0, cross-/HLA-match
2. Medical urgency
3. Organ viability
4. Medical ethics [ Fairness - Efficiency - Equality ]
=> Waiting time, age, “non-resident”, donor accrual.
expertise
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Allocatie Procedure (1)
Patrick Peeters, M.D. – Dept Nephrology Ghent University Hospital, Belgium
Match Programma (computer)
ET Wachtlijst Selectie Hiërarchie
Sorteren
Donor
Orgaan
Matchlijst
Allocatie Procedure (2)
Patrick Peeters, M.D. – Dept Nephrology Ghent University Hospital, Belgium
Aanbied Procedure
Aanbod / Geen aanbod
Aannemen / Weigeren
Matchlijst
Donor
Orgaan Transplantatie / Geen transplantatie
Allocatie Procedure (3)
Patrick Peeters, M.D. – Dept Nephrology Ghent University Hospital, Belgium
HLA-report
Donor Non-Renal Kidney Match Kidney
Report Allocation Cross-match Allocation
20-30 min 2 - 3 hrs 15 min 1.5 - 2.5 hrs
Procurement
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Kidney Allocation factors
HLA-A,B,DR mismatch
Probability
Nier 0&1 HLA-MM
Waiting time punten 0.09 punten per dag wachttijd [ 33 / jaar ]
Ischemia time
Country balance
Patrick Peeters, M.D. – Dept Nephrology Ghent University Hospital, Belgium
punten 400 333 267 200 133 67 0
MM 0 1 2 3 4 5 6
punten 0 100
Kans Klein Groot
punten lokaal nationaal
4/ Kidney transplant patient work-up.
Patrick Peeters, M.D. – Dept Nephrology Ghent University Hospital, Belgium
4 a/ The renal patient
Patrick Peeters, M.D. – Dept Nephrology Ghent University Hospital, Belgium
8/07/2014
32
Equitable Organ Allocation UNOS = United Network for Organ Sharing - USA
maximize patient and graft survival
- minimize deaths while waiting for a transplant
- maximize opportunity for patients with biological or
medical disadvantages to receive a transplant
- minimize disparities in chance of organ offer
among patients with comparable medical and
demographic characteristics
- minimize effects related to geography
- minimize overall transplantation-related costs
=> provide for accountability and public trust
Patrick Peeters, M.D. – Dept Nephrology Ghent University Hospital, Belgium
Guideline 2.1 – Tx : Pre-transplant
assessment UK 2011
We recommend that the object of pre-transplant
assessment is:
a) to ensure transplantation is technically possible;
b) to ensure the recipient’s chances of survival are not
compromised by transplantation;
c) to ensure that graft survival is not limited by premature
death (maximum benefit obtained from a limited
resource);
d) to ensure pre-existing conditions are not exacerbated
by transplantation;
e) to identify measures to be taken to minimise peri- and
post-operative complications; f) to inform patients of
likely risks and benefits of transplantation. (1C)
Patrick Peeters, M.D. – Dept Nephrology Ghent University Hospital, Belgium
Guideline 2.2 – Tx : Pre-transplant
cardiac assessment UK 2011
We suggest that there is no compelling evidence
that in ESRD patients pre-transplantation
screening tests for coronary artery disease in
asymptomatic patients is effective in preventing
future cardiac events or reducing mortality after
transplantation. Until better evidence emerges,
screening tests may be best used to identify high-
risk patients for exclusion from the transplant
waiting list. (2C)
Patrick Peeters, M.D. – Dept Nephrology Ghent University Hospital, Belgium
8/07/2014
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Guideline 2.3 – Tx : Preparation of the
renal transplant recipient UK 2011
We suggest that the use of pre-operative beta-
blockers may be considered in patients at high
cardiovascular risk undergoing renal
transplantation but must be introduced at least 1
month before transplantation. Beta-blockers
should not be discontinued abruptly peri-
operatively. Low dose aspirin therapy is not a
contraindication to transplantation and can be
continued peri-operatively. (2C)
Patrick Peeters, M.D. – Dept Nephrology Ghent University Hospital, Belgium
Guideline 2.4 – Tx : Preparation of the
renal transplant recipient UK 2011
We recommend that patients should be strongly
encouraged to stop smoking before and after
transplantation. Formal smoking cessation
programmes should be offered and accessed in
primary care. (1A)
Patrick Peeters, M.D. – Dept Nephrology Ghent University Hospital, Belgium
Guideline 2.5 – Tx : Preparation of the
renal transplant recipient UK 2011
We recommend that obese patients (BMI >30
kg/m2) present technical difficulties and are at
increased risk of peri-operative complications.
They should be screened rigorously for
cardiovascular disease and each case considered
individually. Although obesity is not an absolute
contra-indication to transplantation, individuals
with a BMI >40 kg/m2 are less likely to benefit.
(1B)
Patrick Peeters, M.D. – Dept Nephrology Ghent University Hospital, Belgium
8/07/2014
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Guideline 2.6 – Tx : Preparation of the
renal transplant recipient UK 2011
We recommend that all potential transplant
recipients should be tested for prior exposure to
viral infections including: CMV, EBV, VZV, HBV,
HCV and (HIV). Immunization should be offered to
all hepatitis B (if not already immunised) and VZ
virus antibody negative patients before
transplantation. Patients otherwise suitable for
renal transplantation with evidence of chronic
hepatitis B and/or C or HIV infection should be
managed according to British TS and Eur BP
Guidelines prior to transplantation. (1A)
Patrick Peeters, M.D. – Dept Nephrology Ghent University Hospital, Belgium
Guideline 2.7 – Tx : Evaluation and
selection of the renal transplant recipient
We recommend that in potential recipients with
previous malignancy (excluding non-melanoma
skin cancer), renal transplantation should only be
considered if there is no evidence of persistent
cancer. It is recommended that the waiting time
between successful tumour treatment/remission
and transplantation be at least 2 years. For certain
malignancies the waiting time may need to be
extended to more than 5 years. The Israel Penn
Transplant Tumour Registry should be consulted
for tumour specific advice (1A)
Patrick Peeters, M.D. – Dept Nephrology Ghent University Hospital, Belgium
(www.ipittr.uc.edu/Home.cfm).
Guideline 2.8 – Tx : Evaluation and
selection of the renal transplant recipient
We recommend that patients who are at risk of
developing recurrence of original renal disease
should be managed according to the European
Best Practice Guidelines (EBPG) and the UK
Guidelines for Living Donor Kidney
Transplantation. (not graded)
Chadban S. Glomerulonephritis recurrence in the renal graft. J Am Soc Nephrol. 2001;
12(2):394-402
European Best Practice Guidelines (EBPG). Nephrol Dial Transplant 2000; 15(7):11-20
http://www.bts.org.uk/transplantation/standards-and-guidelines/
Patrick Peeters, M.D. – Dept Nephrology Ghent University Hospital, Belgium
8/07/2014
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Guideline 2.9 – Tx : Screening investigations
in the renal transplant recipient UK 2011
We suggest that there is no evidence that
asymptomatic potential transplant recipients
require screening for diverticular disease, peptic
ulceration or gall bladder stones. (2C)
Patrick Peeters, M.D. – Dept Nephrology Ghent University Hospital, Belgium
Smoking – Obesity ERBP 2013
Patrick Peeters, M.D. – Dept Nephrology Ghent University Hospital, Belgium
CV disease testing – ERBP 2013
Patrick Peeters, M.D. – Dept Nephrology Ghent University Hospital, Belgium
8/07/2014
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Native nephrectomy – ERBP 2013
Patrick Peeters, M.D. – Dept Nephrology Ghent University Hospital, Belgium
HLA and anti-HLA ERBP 2013
Patrick Peeters, M.D. – Dept Nephrology Ghent University Hospital, Belgium
HLA- matching - ERBP 2013
Patrick Peeters, M.D. – Dept Nephrology Ghent University Hospital, Belgium
8/07/2014
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HLA-matching - ERBP 2013
Patrick Peeters, M.D. – Dept Nephrology Ghent University Hospital, Belgium
Cross-matching ERBP 2013
Patrick Peeters, M.D. – Dept Nephrology Ghent University Hospital, Belgium
Previous transplant explantation? ERBP 2013
Patrick Peeters, M.D. – Dept Nephrology Ghent University Hospital, Belgium
8/07/2014
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HD before Tx - Fluid during Tx - ERBP 2013
Patrick Peeters, M.D. – Dept Nephrology Ghent University Hospital, Belgium
4 a/ The living donor
Patrick Peeters, M.D. – Dept Nephrology Ghent University Hospital, Belgium
The LRD donor – acceptance criteria
Age – variable acceptance
Proteinuria < 100 mg/24h and albuminuria < 30 mg/24h Kasiske AJKD 1995 Klausen Circulation 2004
GFR > 80 ml/min/1.73m³
OGTT normal
No haematuria
Normal blood pressure
BMI < 30
No infectious or cancer risk
Correct social / psychological evaluation
Willingness to donate and follow-up
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ERBP guideline 09/2013
Exercise on a regular basis, lose weight and stop
smoking. (1C)
individual risk of donation carefully discussed with
donor using check list. (US)
donor be evaluated by an independent physician +
psychologist. (US)
process of donation should be stopped if any doubt
on donor safety arise, especially in younger donors,
or when benefit for the recipient is limited. (US)
US ungraded statement
ERBP guideline 09/2013 hypertension
simultaneous presence > 1 risk factor
(hypertension, obesity, proteinuria, impaired
glucose tolerance, haematuria) precludes
donation.(US)
blood pressure <140/90 mmHg on at least 3
occasions without antihypertensive medication, is
normotension. (1C)
measuring ambulatory blood pressure in potential
donors who have office hypertension (BP≥140/90
mmHg) or who are taking pharmacological
treatment for hypertension. (2C) US ungraded statement
ERBP guideline 09/2013 hypertension
well-controlled primary hypertension, <130/85
mmHg, under treatment with maximum 2 anti-
hypertensive drugs (diuretics included) is not
considered a contraindication to living kidney
donation. (2C)
discourage hypertensive donors with evidence of
target organ damage such as left ventricular
hypertrophy, hypertensive retinopathy and micro-
albuminuria.(1C)
suggest that these potential donors could be re-
evaluated for disappearance of this target organ
damage after appropriate treatment. (2D)
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ERBP guideline 09/2013
obesity
BMI >35 kg/m2 is a contraindication to donation.
(2C)
We recommend counseling obese and overweight
donors for weight loss before and after donation.
(US)
US ungraded statement
ERBP guideline 09/2013
impaired glucose tolerance
diabetes mellitus is a contraindication to
donation, other than in exceptional circumstances.
(1D)
impaired glucose tolerance is not an absolute
contraindication to donation. (2C)
ERBP guideline 09/2013
proteinuria
quantify urinary protein excretion in all potential
living donors. (1C)
overt proteinuria is a contraindication for living
donation [24-h total protein >300 mg or spot urinary
albumin to creatinine (mg/g) ratio >300 (>30
mg/mmol)].(1C)
evaluate potential living donors with persistent (> 3
measurements with 3 months interval) proteinuria
<300 mg/24 h by the quantification of micro-
albuminuria to assess their risk of living donation.
(US)
US ungraded statement
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ERBP guideline 09/2013
proteinuria
considering persistent (>3 measurements with 3
months interval) micro-albuminuria (30–300
mg/24 h) a high risk for donation. (US)
US ungraded statement
ERBP guideline 09/2013
haematuria
consider persistent haematuria of glomerular
origin as a contraindication to living donation,
because it may indicate kidney disease in the
donor. (1B)
however, thin basement membrane disease might
be an exception. (US)
US ungraded statement
ERBP guideline 09/2013
old age
old age in itself is not a contraindication to
donation. (1B)
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Expected decline in kidney function due to
ageing
British Transplant Society 2011
Kidney Transplantation - CONCLUSION
PRO:
‣ QOL
‣ prognosis
CON ‣ Risk
‧ Operative risk
‧ Infections
‧ Cancer
‧ CV morbidity/mortality
Long term transplant follow-up
Control BP
Use CCB + ACEi liberally
Control hyperlipidemia
Control weight
Control anaemia
Smoking prevention
Use Aspirin
Worry about the bone
Worry about compliance
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Patrick Peeters, M.D. – Dept Nephrology Ghent University Hospital, Belgium
Q & A