Mempersiapkan transplantasi

ginjal (resipien dan donor)

Dr. Atma Gunawan SpPD.KGH
 Who is recipient ?
• All patient ESRD
• Absolute KI :
- Transplant candidate with cirrhosis
- Active malignancy
- Severe respiratory conditions
- Severe Ischemic heart disease
- Severe peripheral vascular disease
- Severe cognitive impairment
- Active drug or alcohol addiction
- Patient non-adherence to therapy
ALUR KIDNEY Resipien memenuhi syarat
TRANSPLANT ↓
Potential donor
↓
Edukasi dan aspek legal resipien dan donor
↓
Skreening awal resipien dan donor (gol darah, UL, kimia darah,virus
marker, kontraindikasi)
↓
Nephrologist team (skrening lanjutan) : ABO, HLA typing, CM, DSA, PRA,
CT angiografi Renal, MRI aortoiliaka
↓
Transplant team
↓
Approval, tanggal H0
↓
Final crossmatch dan evaluasi pre-operative
↓
Operation
↓
Follow up
 Skreening resipien
• Anamnesa
MRI aortoiliaca
• Pemeriksaan fisik .
• Golongan darah, DL, UL,
LFT,elektrolit serum, gula darah,
profil lipid. Urine culture
• Serologi : hepatitis B dan C,
Syphilis, HIV, CMV, EBV,Herpes
• Radiologi : thoraks, BNO, USG
• Cardiologi : ECG, echo
• Dentis care , endoskopi
• MRI aortoiliaka resipien
• Crossmacth : CDC , luminex
(virtual CM) tes
• Tissue typing : HLA-A, B,C ;
DR,DP,DQ
• Mammografi ( >50 th), PRA (>45
th).
 Histocompatibility test
• Blood typing
• Tissue typing : HLA-A,B,DR
• Panel reactive antibody (PRA)
• Donor specific antibody
• Crossmatch testing
 Blood typing
In cadaveric kidney transplantation,the donor should be ABO identical to
recipient, and ABO blood group compatiblity should be discouraged (level B).

In live donor kidney transplatation, ABO identity or compatibility are equally

accepted (level C)

Donor Resipient
A B AB O

A identical mismatched compatible mismatched

B mismatched identical compatible mismatched

AB mismatched mismatched identical mismatched

O compatible compatible compatible identical

European guideline for kidney transplant 2000

 40%
Oag
anti A Ab
anti B Ab

45% 10%
Aag Bag
(A1 ~36%, A2 ~9%) anti A ab

anti B Ab

The likelihood that two

unrelated individuals are:
AagBag - identical is 37.5%
no Ab - compatible is 26.75%
- incompatible is 35.75%
5%
7
 HLA TYPING (luminex)
HLA TYPING (DONOR) HLA TYPING (RESIPIENT)
No Class Locus HLA No Class Locus HLA
1 Class I HLA-A A*11/A*24 1 Class I HLA-A A*03/A*11
HLA-B B*27/B*44 HLA-B B*35/B*44
HLA-C C*03/C*07 HLA-C C*04/C*05
2 Class II HLA-DR DRB1*12/ 2 Class II HLA-DR DRB1*01/
DRB1*12 DRB1*08
HLA-DQA DQA1*05:01/ HLA- DQA1*01/
DQA1*06:01 DQA DQA1*04
HLA-DQB DQB1*02/ HLA-DQB DQB1*04/
DQB1*03 DQB1*05
HLA-DPA DPA1*01:03/ HLA-DPA DPA1*01/
DPA1*02:02 DPA1*01
HLA-DPB DPB1*02:01/ HLA-DPB DPB1*04/
DPB1*13:01 DPB1*04
HLA typing mismatched: 13/16
HLA typing matched: 3/16 (A*11, /B*44, DPA*01)

8
cPRA 19% ; PRA class I 19%; class II 0%
Why less missmatch is better ?
 Influence of HLA mismatches on the outcome of deceased donor kidney transplants

Craig J. Taylor et al. Phil. Trans. R. Soc. B 2011;366:2312-

2322

©2011 by The Royal Society

 A single sensitizing event can lead to
multiple donor specific antibodies (DSA)

Recipient
HLA-typing: Donor HLA-
typing:
A1,A3
B8, B52 A1,A2
B7,B8 HLA-A2 antibody

+ HLA-B7 antibody
 Detection Donor specific antibodies (DSA) by luminex

HLA ANTIBODY RESIPIEN (TSANIA, 14 TH) HLA TYPING DONOR (SANTI, 50 TH)

No Class Locus HLA

Class Antigen Alele MFI
1 Class I HLA-A A*11/A*24
I B8 HLA-B*08:01 735 HLA-B B*27/B*44
II DR4 DRB1*04:01 360 HLA-C C*03/C*07
DR4 DRB1*04:04 786 2 Class HLA-DR DRB1*12/
II DRB1*12
DR16 DRB1*16:01 881
HLA- DQA1*05:01
DR16 DRB1*16:02 590
DQA /
DR52 DRB3*02:02 350 DQA1*06:01
DP11 DPA1*02:02 1065 HLA- DQB1*02/
DPB1*11:01 DQB DQB1*03
HLA-DPA DPA1*01:03/
DONOR HLA-ANTIBODI NEGATIVE, DPA1*02:03
VIRTUAL CROSS MATCH HLA- DPB1*02:01/
NEGATIVE DPB DPB1*13:01

13
 Interpretation results of antibody
detection assays
• These values can be further categorized into ranges of
strength (i.e. strong, moderate or weak), or simply deemed as
positive or negative.
• There is no consensus regarding positive cutoff values. Each
transplant center currently sets its own MFI threshold for
unacceptable antigens, with most centers selecting an MFI
cutoff between 3000–5000. CTOT study, point to a positive
cut off >1000 MFI for SPA data
• There is not an accepted cutoff for mean fluorescence index
(MFI) of anti-HLA class I and class II antibodies detected by the
SAB assays that has been validated to have clinical
immunological relevance.
Peter S et al. Clin Transplant . 2014 January ; 28(1): 127–133
Kelley M et al. British Medical Bulletin , 2014, 110: 23–34
 Baseline Donor‐Specific Antibody Levels and Outcomes in Positive Crossmatch Kidney Transplantation

Baseline Donor‐Specific Antibody Levels and Outcomes in Positive Crossmatch Kidney Transplantation, Volume: 10, Issue: 3, Pages: 582-589, First published: 16 February
2010, DOI: (10.1111/j.1600-6143.2009.02985.x)
 Interpretation results of antibody
detection assays
• There is insufficient data to determine the meaning of
a DSAb with a negative flow crossmatch
• The presence of a DSAb detected by Luminex in the
setting of a negative CDC crossmatch appears to have
inferior graft survival compared with no DSAb
• Recipients with third party anti-HLA Abs (antibodies
against HLA antigens that are not donor-specific) have
reduced graft survival compared with recipients
without any anti-HLA antibodies
 Graft injury and clinical presentation
after development of de novo donor specific antibody

American Journal of Transplantation 2014; 14: 255–271

 Probability of graft loss within 3 years after de novo
donor specific- human leukocyte antigens antibodies
appearance..

DSA:Donorspecific- human leukocyte antigens antibodies

World J Transplant 2014 March 24; 4(1): 1-17
 Cross-match Scenario
• Cross-match negative → proceed to Transplant

• Cross-match positive → Contraindication

 Method for crossmatching

1. Basic CDC (complement dependent

cytotoxity crossmatch)
2. Isolated T and B cells CDC XM
3. AHG-CDC
4. DTT-CDC
5. Flow cytometry CM
6. Virtual crossmatch
 Basic CDC
• First generation
• Unable to distinguish between donor T cell and B cell populations
• Unable to differentiate IgG from IgM
• Low accuracy
AHG-CDC
Hasil Tn. Mujianto (AHG-CDC XM positif)
Flow Cytometric crossmatch
 Flow cytometry XM (Tsania,14 th)
Sel T Sel B

Kontrol negatif Kontrol negatif

(MCF 10,38) (MCF 33,38)

Kontrol positif Kontrol positif

(MCF 20,93) (MCF 53,91)

Donor resipien Donor resipien

(MCF 11,19) (MCF 35,38
Interpretation of Crossmatch (CDC) result
T-Cell B-Cell Interpretation
XM XM
-ve -ve No DSAb to HLA class I or II OR
DSAb titre too low to cause
positive reaction OR
(DSAb that is not complement-
fixing – relevance unclear)

+ve +ve DSAb/s to HLA class I OR

Multiple DSAbs to HLA class I
+/- II

-ve +ve DSAb/s to HLA class II OR

Low level DSAb/s to HLA class I

+ve -ve Technical error (possibly

related to B-cell viability).
The test should be repeated
Positive T-cell crossmatch is likely to
generate hyperacute rejection
 The relevance of a positive B-cell CDC
crossmatch
• B-cell CDC crossmatching is not as predictive of HAR as the T-cell
CDC crossmatch
• The major limitation is a rate of false positive results of up to 50%.
• Antibodies to class II antigens are of less significance in generating
antibody-mediated rejection
• B-cell CM + should be paired with Solid-Phase Immunoassays (ex
Luminex) to reveal presence of DSAbs
• If a B-cell crossmatch is positive and there are no detectable
antibodies to class I or II antigens, the result may be falsely positive
• If a positive result in the presence of detectable DSAbs signifies that
the identified DSAb may be functionally relevant in that it can
activate complement
 Interpretation Flow cytometric
Crossmatch Results
1. Positive T-cell flow crossmatch suggests that
there is a DSAb to a class I antigen
2. Positive B-cell crossmatch may be due to the
same class I Ab or due to that and other
antibodies directed against either class I or II.
3. In case CDC XM T & B cell negative but Flow XM cell
T&B positive :
- There is a low-level DSAb (or several antibodies)
- There is/are one or more DSAb that are not
complement fixing
- There is non-HLA antibody
Immunological risks

Clinical Guidelines for Kidney Transplantation 2015

 Transplantation risk stratification
Transplantation risk stratification categories should be
developed based on antibody identification and XM
results

1. Very high risk patients (DSA positive/XM positive)

2. High-risk patients (DSA positive/XM negative)
3. Intermediate-risk patients: Includes history of
sensitization to donor antigen(s) by CDC and SPI but
currently negative and history of sensitization with at
least one positive test for HLA antibodies.
4. Low-risk patients (DSA negative/XM negative, history
sensitization negative)
Consensus Guidelines on the Testing and Clinical Management Issues Transplantation & Volume 95, Number 1, January 15, 2013
Associated With HLA and Non-HLA Antibodies in Transplantation
 Immunological Criteria Theraphy
Risk
Low risk Low-risk patients (DSA negative/XM Initial therapy: IL-2 receptor
negative, history sensitization negative) blocker (basiliximab), a
0-1 DR mismatchs calcineurin inhibitor,
PRA < 20% mycophenolate
mofetil,steroids. Then a rapid
steroid elimination protocol
No basiliximab for identical
HLA match

Intermediate Risk Intermediate-risk patients :(DSA Quadriple therapy : IL-2

negative/XM negative, history receptor blocker (basiliximab),
sensitization positive : history of a calcineurin inhibitor ,
sensitization to donor antigen(s) by CDC prednisone, and
and SPI but currently negative and mycophenolate mofetil (MMF)
history of sensitization with at least one
positive test for HLA antibodies
PRA 20% - 80%

High Risk Second transplant (1 or more rejection Quadriple therapy consisting

within the first year post transplantation) of an anti-thymocyte globulin
Any recipients PRA > 80% (Thymoglobulin®), a
DSA positive/XM negative calcineurin inhibitor ,
2 DR mismatch, 6 HLA mismatch prednisone, and MMF
 Immunological risk Criteria Theraphy
Sensitized patient DSA positive/XM positive IVIG ± rituximab ±
plasmapheresis or
immunoadsorption ±
induction with T-cell
depleting antibody

Sensitized patient ABO incompatible living- Rituximab ± IVIG ±

donor transplants plasmapheresis or
immunoadsorption

High Donor Risk Donors at high risk for Anti- thymocyte globulin 1.0
delayed graft function to 1.5 mg/kg begin as soon
Donor age greater than 60 as possible in operating-
years, acute kidney injury room or immediately post-
and prolonged cold transplant and day 4.
ischemic time May receive one dose of
tacrolimus immediate
release + mycophenolate
mofetil prior to surgery
Start Tacrolimus when renal
function is established
 Donor evaluation steps
Interested Donor

ABO Blood Type Compatible

HLA (Tissue Type) Compatibility

Full Nephrology Review Including Blood and X-Ray Test

Phsycology Review and legal aspect

CT angiography renal

Surgical Review

Final Cross Match

PROCEED TO TRANSPLANTATION
 Medical Examination
Anamnesis
• Haematuria/proteinuria/urinary tract
infection
• Gout, Nephrolithiasis
• Diabetes mellitus, including family history
• Hypertension, Ischaemic heart
disease/peripheral vascular disease
• Weight change, Change in bowel habit
• Previous malignancy, Previous jaundice
• Systemic disease which may involve the
kidney
• History transmissible infection
• Smoking, Current or prior alcohol or drug
dependence
• Psychiatric history, sexual behaviour
• Obstetric history
• Results of national screening programme
tests e.g. cervical smear,
mammography,colorectal screening
Physical examanation
• Blood pressure measurement
• Body mass index
• Abdominal fat distribution
• Examination of the cardiovascular
and respiratory systems
• Examination for abdominal masses
or herniae
• Examination for scars or previous
surgery
• Examination for lymphadenopathy
• Examination / history of regular
self-examination of the breasts
• Examination / history of regular
self-examination of the testes
 Laboratory screening for the potential donor

Blood Urine
• Haemoglobin and blood count • Urinalysis (protein, blood
• Coagulation screen (PT and APTT)
• Creatinine, urea and electrolytes
and glucose ) at least twice)
• Measurement of GFR • Microscopy, culture and
• Liver function tests sensitivity (at least twice)
• Bone profile (calcium, phosphate, albumin
and alkaline phosphatase) • Measurement of protein
• Urate excretion rate (ACR or PCR)
• Fasting plasma glucose
• Glucose tolerance test (if family history of
diabetes or fasting plasma glucose >5.6
mmol/l)
• Lipid profile
• Thyroid function tests (if strong family
history)
• Pregnancy test (if indicated)
 Additional screening
Virology and infection screen Imaging, psychosocial, cancer
• Hepatitis B and C • Chest X-Ray and
• HIV Electrocardiogram (EKG)
• Cytomegalovirus • Radiologic Testing: USG
• Epstein-Barr virus
urology, CT renal angiography
,IVP, MRI, and arteriogram
• Toxoplasma
• Psychosocial and/or
• Syphilis psychological evaluation
• Varicella zoster virus (where recipient • Gynecological screening for
seronegative) female
• HTLV1 and 2 (if appropriate) • Cancer screening: may include
• HHV8 (where indicated) a colonoscopy, mammogram,
• Malaria (where indicated) prostate exam, and skin cancer
• Trypanosoma cruzi (where indicated) screening
• Schistosomiasis (where indicated)
 CT renal angioraphy
Surgical Imaging aims :
- To choose the kidney
with single artery,
more lengthy artery,
absent pelvi-calyceal
and vessels anomalies,
lower split function
 Relative or absolute contraindications to
live kidney donations
• Age < 18-25 or > 70-75 years
• Low GFR (<70 ml/min)
• Hypertension (BP >140/90 mmHg) or on antihypertensive
medications
• BMI > 30-35
• DM or abnormal glucose tolerance test
• History of gestasional DM
• Malignacy
• Microalbuminuria
• Recurrent kidney stones
• Trasmissable serious infections (HIV, hepatitis C, hepatitis B)
Acceptable GFR by donor age prior
to donation www.bts.org

Donor age Acceptable

(years) corrected GFR
prior to
donation
(ml/min/1.73
m2)
Up to 46 80
50 77
60 68
70 59
80 50
Impact Of Donor Old Age On Renal Transplant
Outcome

American Journal of Transplantation 2011; 11: 1279–1286

 HYPERTENSION IN THE DONOR
• Potential donors with blood pressure <140/90 mmHg should be considered as
normotensive and therefore suitable for nephrectomy on the basis of blood
pressure. (B1)
• Potential donors with ‘high normal’ blood pressure (>130/85 mmHg) should be
warned about the greater future risk of developing hypertension and associated
cardiovascular events (B1)
• Office blood pressure measurements are sufficient for the assessment of the
majority of potential donors. Ambulatory blood pressure monitoring should be
considered for potential donors who have hypertension (blood pressure greater
than 140/90 mmHg or who are taking pharmacological treatment for
hypertension) and if this is normal (see below) donor nephrectomy is not
precluded. (B1)
• The presence of mild-moderate hypertension that is controlled with 1-2
antihypertensive agents is not a contraindication to kidney donation providing
significant end organ damage has been excluded. (B1)
• Evidence of hypertensive end organ damage, poorly controlled hypertension, or
hypertension that requires more than two drugs to achieve adequate control are
relative contraindications to donor nephrectomy. (C2)
 PROTEINURIA (ERBP 2013)
• We recommend quantifying urinary protein excretion in all
potential living donors. (1C)
• We recommend 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)
• We recommend further evaluating potential living donors with
persistent (more than three measurements with 3 months interval)
proteinuria <300 mg/24 h by the quantification of
microalbuminuria to assess their risk of living donation. (Ungraded
statement)
• We suggest considering persistent (more than three measurements
with 3 months interval) micro-albuminuria (30– 300 mg/24 h) a
high risk for donation. (Ungraded statement)
 Hematuria (ERBP 2013)
• We recommend considering persistent haematuria of
glomerular origin as a contraindication to living
donation, because it may indicate kidney disease in
the donor. (1B)
• Two or more positive tests, including trace positive,
should be considered as persistent non-visible
haematuria (PNVH). (B1)
• However, we acknowledge thin basement membrane
disease might be an exception. (Ungraded
statement)
Wassalam