Mempersiapkan transplantasi ginjal (resipien dan … resipien • Anamnesa • Pemeriksaan fisik . • Golongan darah, DL, UL, LFT,elektrolit serum, gula darah, profil lipid. Urine
Post on 02-Mar-2019
252 Views
Preview:
Transcript
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
Resipien memenuhi syarat
↓
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
ALUR KIDNEY TRANSPLANT
Skreening resipien
• Anamnesa
• 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).
MRI aortoiliaca
Histocompatibility test
• Blood typing
• Tissue typing : HLA-A,B,DR
• Panel reactive antibody (PRA)
• Donor specific antibody
• Crossmatch testing
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
Blood typing
European guideline for kidney transplant 2000
7
Oag
anti A Ab
anti B Ab
AagBag
no Ab
Aag
(A1 ~36%, A2 ~9%)
anti B Ab
Bag
anti A ab
40%
5%
45% 10%
The likelihood that two
unrelated individuals are:
- identical is 37.5%
- compatible is 26.75%
- incompatible is 35.75%
HLA TYPING (luminex)HLA TYPING (DONOR)
No Class Locus HLA
1 Class I HLA-A A*11/A*24
HLA-B B*27/B*44
HLA-C C*03/C*07
2 Class II HLA-DR DRB1*12/DRB1*12
HLA-DQA DQA1*05:01/DQA1*06:01
HLA-DQB DQB1*02/DQB1*03
HLA-DPA DPA1*01:03/DPA1*02:02
HLA-DPB DPB1*02:01/DPB1*13:01
HLA TYPING (RESIPIENT)
No Class Locus HLA
1 Class I HLA-A A*03/A*11
HLA-B B*35/B*44
HLA-C C*04/C*05
2 Class II HLA-DR DRB1*01/DRB1*08
HLA-DQA
DQA1*01/DQA1*04
HLA-DQB DQB1*04/DQB1*05
HLA-DPA DPA1*01/DPA1*01
HLA-DPB DPB1*04/DPB1*04
HLA typing mismatched: 13/16HLA 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
Donor HLA-
typing:
A1,A2
B7,B8
Recipient
HLA-typing:
A1,A3
B8, B52
+
HLA-A2 antibody
HLA-B7 antibody
A single sensitizing event can lead to
multiple donor specific antibodies (DSA)
Detection Donor specific antibodies (DSA) by luminex
HLA ANTIBODY RESIPIEN (TSANIA, 14 TH)
Class Antigen Alele MFI
I B8 HLA-B*08:01 735
II DR4 DRB1*04:01 360
DR4 DRB1*04:04 786
DR16 DRB1*16:01 881
DR16 DRB1*16:02 590
DR52 DRB3*02:02 350
DP11 DPA1*02:02DPB1*11:01
1065
HLA TYPING DONOR (SANTI, 50 TH)
13
No Class Locus HLA
1 Class I HLA-A A*11/A*24
HLA-B B*27/B*44
HLA-C C*03/C*07
2 Class II
HLA-DR DRB1*12/DRB1*12
HLA-DQA
DQA1*05:01/DQA1*06:01
HLA-DQB
DQB1*02/DQB1*03
HLA-DPA DPA1*01:03/DPA1*02:03
HLA-DPB
DPB1*02:01/DPB1*13:01
DONOR HLA-ANTIBODI NEGATIVE,
VIRTUAL CROSS MATCH NEGATIVE
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): 127–133Kelley 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 presentationafter 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(MCF 10,38)
Kontrol positif(MCF 20,93)
Donor resipien(MCF 11,19)
Kontrol negatif(MCF 33,38)
Kontrol positif(MCF 53,91)
Donor resipien(MCF 35,38
Interpretation of Crossmatch (CDC) result
T-CellXM
B-CellXM
Interpretation
-ve
+ve
-ve
+ve
-ve
+ve
+ve
-ve
No DSAb to HLA class I or II ORDSAb titre too low to cause positive reaction OR(DSAb that is not complement-fixing – relevance unclear)
DSAb/s to HLA class I ORMultiple DSAbs to HLA class I +/- II
DSAb/s to HLA class II ORLow level DSAb/s to HLA class I
Technical error (possibly related to B-cell viability).The test should be repeated
Positive T-cell crossmatch is likely togenerate 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 thatthere 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 otherantibodies 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 Associated With HLA and Non-HLA Antibodies in Transplantation
Transplantation & Volume 95, Number 1, January 15, 2013
Immunological
Risk
Criteria Theraphy
Low risk Low-risk patients (DSA negative/XM
negative, history sensitization negative)
0-1 DR mismatchs
PRA < 20%
Initial therapy: IL-2 receptor
blocker (basiliximab), a
calcineurin inhibitor,
mycophenolate
mofetil,steroids. Then a rapid
steroid elimination protocol
No basiliximab for identical
HLA match
Intermediate Risk Intermediate-risk patients :(DSA
negative/XM negative, history
sensitization positive : 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
PRA 20% - 80%
Quadriple therapy : IL-2
receptor blocker (basiliximab),
a calcineurin inhibitor ,
prednisone, and
mycophenolate mofetil (MMF)
High Risk Second transplant (1 or more rejection
within the first year post transplantation)
Any recipients PRA > 80%
DSA positive/XM negative
2 DR mismatch, 6 HLA mismatch
Quadriple therapy consisting
of an anti-thymocyte globulin
(Thymoglobulin®), a
calcineurin inhibitor ,
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-
donor transplants
Rituximab ± IVIG ±
plasmapheresis or
immunoadsorption
High Donor Risk Donors at high risk for
delayed graft function
Donor age greater than 60
years, acute kidney injury
and prolonged cold
ischemic time
Anti- thymocyte globulin 1.0
to 1.5 mg/kg begin as soon
as possible in operating-
room or immediately post-
transplant and day 4.
May receive one dose of
tacrolimus immediate
release + mycophenolate
mofetil prior to surgery
Start Tacrolimus when renal
function is established
Donor evaluation stepsInterested 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 • Haemoglobin and blood count
• Coagulation screen (PT and APTT)
• Creatinine, urea and electrolytes
• Measurement of GFR
• Liver function tests
• Bone profile (calcium, phosphate, albumin and alkaline phosphatase)
• Urate
• 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)
Urine
• Urinalysis (protein, blood and glucose ) at least twice)
• Microscopy, culture and sensitivity (at least twice)
• Measurement of protein excretion rate (ACR or PCR)
Additional screening
Virology and infection screen
• Hepatitis B and C
• HIV
• Cytomegalovirus
• Epstein-Barr virus
• Toxoplasma
• Syphilis
• Varicella zoster virus (where recipient seronegative)
• HTLV1 and 2 (if appropriate)
• HHV8 (where indicated)
• Malaria (where indicated)
• Trypanosoma cruzi (where indicated)
• Schistosomiasis (where indicated)
Imaging, psychosocial, cancer• Chest X-Ray and
Electrocardiogram (EKG)• Radiologic Testing: USG
urology, CT renal angiography ,IVP, MRI, and arteriogram
• Psychosocial and/or psychological evaluation
• Gynecological screening for female
• Cancer screening: may include a colonoscopy, mammogram, prostate exam, and skin cancer screening
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 (years)
Acceptable 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 themajority 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 forhypertension) and if this is normal (see below) donor nephrectomy is notprecluded. (B1)
• The presence of mild-moderate hypertension that is controlled with 1-2antihypertensive 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
top related