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Principles Of Transplant Preparation
(Recipient)
DR. AHMED AKL, MD, FACP
Educational Ambassador,
Consultant Of Nephrology & Transplantation,
Urology & Nephrology Center,
Mansoura,
Egypt
 In 1954, the first successful kidney
transplantation was performed using a kidney
from a living donor: the identical twin of the
recipient.
HISTORY
First Transplanted Patient in Mansoura
(27 Mar 1976)
CURRENT
• 2800 living donor transplant recipients [100 per year].
Donor nephrectomy
Kidney graft perfusion
Transplantation
ADVANTAGES OF
TRANSPLANTATION
 Better quality of life - freedom from dialysis.
 Avoid long-term complications of dialysis.
 Higher energy levels.
 Less dietary and fluid restrictions.
 PATIENTS SURVIVAL:
• Chronic dialysis :
-mortality rate of 6-20% per year and as high as 11-25%. per year in diabetic
patients.
• Renal transplantation:
-Operative mortality rate of less than 2%.
-The 1-year survival for recipients of living related kidneys is better than 95%.
-The 5-year patient survivals are approximately 80% for nondiabetic recipients
and 60-70% for diabetic recipients.
The Major Histocompatibility
Complex (MHC)
 THE CLASS I REGION encodes more than 15 genes:
-The classical transplant genes A, B, and C.
-HLA-E, F, and G.
-Pseudogenes, H, J, K, and L.
 THE CLASS II REGION contains more than 25 genes:
-The transplantation antigens HLA-DR, DQ, and DP.
-The region also includes two alpha genes, DMA and DNA,
-Two beta genes, DMB and DOB, genes for the low-molecular-weight
proteins (LMPs) LMP2 and LMP3
-The transporter molecules TAP1 and TAP2.
 THE CLASS III REGION, lying between class II and class I, >30 genes:
-The genes encoding the complement components factor B, C2, and
both C4 molecules,
-Both tumor necrosis factor genes alpha and beta,
-The heat shock proteins Hsp 1H and Hsp 70 2, and 21-hydroxylase.
• Each gene has multiple, dominant alleles. Histocompatibility genes
and the proteins they encode are highly polymorphic (i.e., they exist
in multiple forms).
The Major Histocompatibility Complex (MHC)
The Major Histocompatibility Complex (MHC)
 Hyperacute rejection (24-48hours):
-Mediated by preformed cytotoxic antibody.
-It can be screened for by cross-matching
procedures.
REJECTION
• Much of the susceptibility of
lymphocytes to immunosuppression is
due to the vast cellular changes that
follow immune stimulation. The
biosynthetic events that take place
make the lymphocytes vulnerable to
inhibition at various stages of the cell
cycle.
Kidney Transplantation
Deceased/Cadaveric
Living
UnrelatedRelated
DONOR
ISN EDUCATIONAL AMBASSADOR PROGRAM –
WADMEDANI –SUDAN 22-26 SEP 2017
❖ History
❖ Clinical examination
Medical Assessment
PatientDonor
ISN EDUCATIONAL AMBASSADOR PROGRAM –
WADMEDANI –SUDAN 22-26 SEP 2017
 Blood group-(Rh).
 Cross-match.
 Tissue typing(HLA-DR).
ABO blood grouping and cross-match testing
PatientDonor
ISN EDUCATIONAL AMBASSADOR PROGRAM –
WADMEDANI –SUDAN 22-26 SEP 2017
Donor
Hanks
Mononuclear
cell layer
Ficoll
Recipient
Serum
Anti-human
globulin
antibodies
23
o
C30
23
o
C
60
Anti-human
Globulin Enhanced
Crossmatch
Wash x 3
Rabbit
complementC
Laser
Cells
Flow chamber
Laser activated
fluorochromes
emit light in red
or green
spectrum
Flow Crossmatch
Donor cells are
incubated with
recipient serum
and then
fluorochrome-
coated antihuman
antibodies
FLOW CYTOMETRY CROSS MATCH
ISN EDUCATIONAL AMBASSADOR PROGRAM –
WADMEDANI –SUDAN 22-26 SEP 2017
RECIPINT EVALUATION
• CARDIAC
• CEREBROVASCULAR
• MALIGNANCY
• INFECTIONS
• GASTROINTESNAL
• PULMONARY
• UROLOGIC EVALUATION
• RENAL OSTEODYSTROPHY AND METABOLIC BONE DISEASE
ECG & Echocardiography
ISN EDUCATIONAL AMBASSADOR PROGRAM –
WADMEDANI –SUDAN 22-26 SEP 2017
HIGH CARDIOVASCULAR RISK RENAL TRANSPLANT CANDIDATE
SYMPTOMATIC ISCHEMIC
HEART DISEASE
ASYMPTOMATIC
CORONARY
ANGIOGRAPHY
MYOCARDIAL
PERFUSION STUDY
POSITIVENEGATIVE
CAD WITH L MAIN
OR EQUIVALENT
STENOSIS
CAD >70% EXCLUDING
L MAIN OR EQUIVALENT
STENOSISCAD LESIONS
<70%
NORMAL CA
TRANSPLANT
REVASCULARIZE
PREFERENCE FOR
CABG
SUCCESSFUL
REVASCULARIZATION
SYMPTOMATIC
POSITIVE MPS
CARDIAC REVIEW
REVASCULARIZATI
ON BENEFICIAL
REVASCULARIZATIO
N NOT BENEFICIAL
ASYMPTOMATIC
NEGATIVE MPS
OPTIMIZE MEDICAL
MANAGEMENT
ASPIRIN BETA
BLOCKADE STATIN
CONSIDER ACEI
ISN EDUCATIONAL AMBASSADOR,
WADMEDANI, SUDAN 22-26 SEPT 2017
RECOMMENDATIONS FOR MINIMUM TUMOUR–FREE WAITING
PERIODS FOR COMMON PRETRANSPLANTATION MALIGNANCIES
RENAL
WILMS TUMOR 2 YEARS
RENAL CELL CARCINOMA NONE (INCIDENTAL TUMORS)
BLADDER
IN SITU NONE
INVASIVE 2 YEARS
UTERUS
CERVIX (IN SITU) NONE
CERVICAL INVASIVE 2-5 YEARS
UTERINE BODY 2 YEARS
BREAST 2-5 YEARS
COLORECTAL 2-5 YEARS
LYMPHOMA 2-5 YEARS
SKIN (LOCAL)
BASAL CELL NONE
SQUAMOUS CELL SURVEILLANCE
MELANOMA 5 YEARS
TUMOR TYPE MINIMAL WAIT TIME
ISN EDUCATIONAL AMBASSADOR,
WADMEDANI, SUDAN 22-26 SEPT 2017
RISK FOR RECURRENT DISEASE AFTER RENAL
TRANSPLANTATION
FSGS 30-50
IgA NEPHROPATHY 40-60
MPGN-I 30-50
MPGN-II 80-100
MEMBRANOUS NEPHROPATHY 10-30
DIABETIC NEPHROPATHY 80-100 (BY HISTOLOGY)
HUS/TTP 50-75
OXALOSIS 80-100
WEGENER DISEASE <20
FABRY DISEASE <5
SLE 3-10
RECURRENT DISEASE RISK (%)
ISN EDUCATIONAL AMBASSADOR,
WADMEDANI, SUDAN 22-26 SEPT 2017
INDICATIONS FOR PRETRANSPLANTATION NATIVE
NEPHRECTOMY
 Chronic renal parenchymal infection.
 Infected stones.
 Heavy proteinuria.
 Intractable hypertension.
 Polycystic kidney disease.
 Acquired renal cystic disease.
 Infected reflux.
ISN EDUCATIONAL AMBASSADOR,
WADMEDANI, SUDAN 22-26 SEPT 2017
ISN EDUCATIONAL AMBASSADOR,
WADMEDANI, SUDAN 22-26 SEPT 2017
MAJOR CONTRAINDICATIONS TO KIDNEY TRANSPLANTATION
 RECENT OR METASTATIC MALIGNANCY.
 UNTREATED CURRENT INFECTION.
 SEVERE IRREVERSIBLE EXTRARENAL DISEASE.
 PSYCHIATRIC ILLNESS IMPAIRING CONSENT AND ADHERENCE.
 CURRENT RECREATIONAL DRUG ABUSE.
 AGGRESSIVE RECURRENT NATIVE KIDNEY DISEASE.
 PRIMARY OXALOSIS
Elements of Securing Informed Consent
• Ensuring the participant’s understanding of the procedure
& sequelae.
• Confirming the participant’s medical & psychological
suitability.
• Educating the donor.
• Ensuring the absence of coercion and free choice.
• Documenting informed consent.
Mansoura Policy
‫عائلتها‬ ‫أفراد‬ ‫ألحد‬ ‫زوجة‬ ‫تبرع‬ ‫حالة‬ ‫فى‬
‫التب‬ ‫على‬ ‫الزوج‬ ‫وتوقيع‬ ‫موافقة‬ ‫يشترط‬‫رع‬
CAN WE PREDICT RENAL TRANSPLANTATION OUTCOME?
EQUATION BUILT FROM FRENCH DIVAT
DATABASE
VALIDATED ON UNOS
DATABASE
41-50
31-40
<=30
>50
Recipient age
Donor age
Haplotype
Time to diuresis
Total steroid dose
Immunosuppression
ATN
Number of acute rejection
Points
Total Points
5-Year graft survival Prob
21-30
31-40
>50
<=20
41-50
One haplotype MM(R)
HLA-identical sibling Two haplotype MM(R+UR)
Immediate
Delayed
<5 gm
5-10 gm
>10 gm
FK
Rapa
Aza
CsA
Triple
No
Yes
No rejection
One rejection
More than one rejection
0 50 100 150 200 250 300 350
0.95 0.9 0.8 0.7 0.6 0.5 0.4 0.3
0 10 20 30 40 50 60 70 80 90 100
Total points: 4060100115210220
COX REGRESSION BASED NOMOGRAM
41-50
31-40
<=30
>50Recipient age
Donor age
Haplotype
Time to diuresis
Total steroid dose
Immunosuppression
ATN
Number of acute rejection
Points
Total Points
1-Year graft survival Prob
2-Year graft survival Prob
3-Year graft survival Prob
4-Year graft survival Prob
5-Year graft survival Prob
21-30
31-40
>50
<=20
41-50
One haplotype MM(R)
HLA-identical sibling Two haplotype MM(R+UR)
Immediate
Delayed
<5 gm
5-10 gm
>10 gm
FK
Rapa
Aza
CsA
Triple
No
Yes
No rejection
One rejection
More than one rejection
0 50 100 150 200 250 300 350
0.95 0.9 0.8 0.7
0.95 0.9 0.8 0.7 0.6
0.95 0.9 0.8 0.7 0.6 0.5
0.95 0.9 0.8 0.7 0.6 0.5 0.4
0.95 0.9 0.8 0.7 0.6 0.5 0.4 0.3
0 10 20 30 40 50 60 70 80 90 100
Akl et al., Exp Clin Transplant, 2008
COX REGRESSION BASED NOMOGRAM
Thank You

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Preparation kidney tx_recipient_drakl

  • 1. Principles Of Transplant Preparation (Recipient) DR. AHMED AKL, MD, FACP Educational Ambassador, Consultant Of Nephrology & Transplantation, Urology & Nephrology Center, Mansoura, Egypt
  • 2.  In 1954, the first successful kidney transplantation was performed using a kidney from a living donor: the identical twin of the recipient. HISTORY
  • 3. First Transplanted Patient in Mansoura (27 Mar 1976)
  • 4. CURRENT • 2800 living donor transplant recipients [100 per year]. Donor nephrectomy Kidney graft perfusion Transplantation
  • 5. ADVANTAGES OF TRANSPLANTATION  Better quality of life - freedom from dialysis.  Avoid long-term complications of dialysis.  Higher energy levels.  Less dietary and fluid restrictions.  PATIENTS SURVIVAL: • Chronic dialysis : -mortality rate of 6-20% per year and as high as 11-25%. per year in diabetic patients. • Renal transplantation: -Operative mortality rate of less than 2%. -The 1-year survival for recipients of living related kidneys is better than 95%. -The 5-year patient survivals are approximately 80% for nondiabetic recipients and 60-70% for diabetic recipients.
  • 7.  THE CLASS I REGION encodes more than 15 genes: -The classical transplant genes A, B, and C. -HLA-E, F, and G. -Pseudogenes, H, J, K, and L.  THE CLASS II REGION contains more than 25 genes: -The transplantation antigens HLA-DR, DQ, and DP. -The region also includes two alpha genes, DMA and DNA, -Two beta genes, DMB and DOB, genes for the low-molecular-weight proteins (LMPs) LMP2 and LMP3 -The transporter molecules TAP1 and TAP2.  THE CLASS III REGION, lying between class II and class I, >30 genes: -The genes encoding the complement components factor B, C2, and both C4 molecules, -Both tumor necrosis factor genes alpha and beta, -The heat shock proteins Hsp 1H and Hsp 70 2, and 21-hydroxylase. • Each gene has multiple, dominant alleles. Histocompatibility genes and the proteins they encode are highly polymorphic (i.e., they exist in multiple forms). The Major Histocompatibility Complex (MHC)
  • 9.  Hyperacute rejection (24-48hours): -Mediated by preformed cytotoxic antibody. -It can be screened for by cross-matching procedures. REJECTION • Much of the susceptibility of lymphocytes to immunosuppression is due to the vast cellular changes that follow immune stimulation. The biosynthetic events that take place make the lymphocytes vulnerable to inhibition at various stages of the cell cycle.
  • 10. Kidney Transplantation Deceased/Cadaveric Living UnrelatedRelated DONOR ISN EDUCATIONAL AMBASSADOR PROGRAM – WADMEDANI –SUDAN 22-26 SEP 2017
  • 11. ❖ History ❖ Clinical examination Medical Assessment PatientDonor ISN EDUCATIONAL AMBASSADOR PROGRAM – WADMEDANI –SUDAN 22-26 SEP 2017
  • 12.  Blood group-(Rh).  Cross-match.  Tissue typing(HLA-DR). ABO blood grouping and cross-match testing PatientDonor ISN EDUCATIONAL AMBASSADOR PROGRAM – WADMEDANI –SUDAN 22-26 SEP 2017
  • 14. Laser Cells Flow chamber Laser activated fluorochromes emit light in red or green spectrum Flow Crossmatch Donor cells are incubated with recipient serum and then fluorochrome- coated antihuman antibodies
  • 16. ISN EDUCATIONAL AMBASSADOR PROGRAM – WADMEDANI –SUDAN 22-26 SEP 2017 RECIPINT EVALUATION • CARDIAC • CEREBROVASCULAR • MALIGNANCY • INFECTIONS • GASTROINTESNAL • PULMONARY • UROLOGIC EVALUATION • RENAL OSTEODYSTROPHY AND METABOLIC BONE DISEASE
  • 17. ECG & Echocardiography ISN EDUCATIONAL AMBASSADOR PROGRAM – WADMEDANI –SUDAN 22-26 SEP 2017
  • 18. HIGH CARDIOVASCULAR RISK RENAL TRANSPLANT CANDIDATE SYMPTOMATIC ISCHEMIC HEART DISEASE ASYMPTOMATIC CORONARY ANGIOGRAPHY MYOCARDIAL PERFUSION STUDY POSITIVENEGATIVE CAD WITH L MAIN OR EQUIVALENT STENOSIS CAD >70% EXCLUDING L MAIN OR EQUIVALENT STENOSISCAD LESIONS <70% NORMAL CA TRANSPLANT REVASCULARIZE PREFERENCE FOR CABG SUCCESSFUL REVASCULARIZATION SYMPTOMATIC POSITIVE MPS CARDIAC REVIEW REVASCULARIZATI ON BENEFICIAL REVASCULARIZATIO N NOT BENEFICIAL ASYMPTOMATIC NEGATIVE MPS OPTIMIZE MEDICAL MANAGEMENT ASPIRIN BETA BLOCKADE STATIN CONSIDER ACEI ISN EDUCATIONAL AMBASSADOR, WADMEDANI, SUDAN 22-26 SEPT 2017
  • 19. RECOMMENDATIONS FOR MINIMUM TUMOUR–FREE WAITING PERIODS FOR COMMON PRETRANSPLANTATION MALIGNANCIES RENAL WILMS TUMOR 2 YEARS RENAL CELL CARCINOMA NONE (INCIDENTAL TUMORS) BLADDER IN SITU NONE INVASIVE 2 YEARS UTERUS CERVIX (IN SITU) NONE CERVICAL INVASIVE 2-5 YEARS UTERINE BODY 2 YEARS BREAST 2-5 YEARS COLORECTAL 2-5 YEARS LYMPHOMA 2-5 YEARS SKIN (LOCAL) BASAL CELL NONE SQUAMOUS CELL SURVEILLANCE MELANOMA 5 YEARS TUMOR TYPE MINIMAL WAIT TIME ISN EDUCATIONAL AMBASSADOR, WADMEDANI, SUDAN 22-26 SEPT 2017
  • 20. RISK FOR RECURRENT DISEASE AFTER RENAL TRANSPLANTATION FSGS 30-50 IgA NEPHROPATHY 40-60 MPGN-I 30-50 MPGN-II 80-100 MEMBRANOUS NEPHROPATHY 10-30 DIABETIC NEPHROPATHY 80-100 (BY HISTOLOGY) HUS/TTP 50-75 OXALOSIS 80-100 WEGENER DISEASE <20 FABRY DISEASE <5 SLE 3-10 RECURRENT DISEASE RISK (%) ISN EDUCATIONAL AMBASSADOR, WADMEDANI, SUDAN 22-26 SEPT 2017
  • 21. INDICATIONS FOR PRETRANSPLANTATION NATIVE NEPHRECTOMY  Chronic renal parenchymal infection.  Infected stones.  Heavy proteinuria.  Intractable hypertension.  Polycystic kidney disease.  Acquired renal cystic disease.  Infected reflux. ISN EDUCATIONAL AMBASSADOR, WADMEDANI, SUDAN 22-26 SEPT 2017
  • 22. ISN EDUCATIONAL AMBASSADOR, WADMEDANI, SUDAN 22-26 SEPT 2017 MAJOR CONTRAINDICATIONS TO KIDNEY TRANSPLANTATION  RECENT OR METASTATIC MALIGNANCY.  UNTREATED CURRENT INFECTION.  SEVERE IRREVERSIBLE EXTRARENAL DISEASE.  PSYCHIATRIC ILLNESS IMPAIRING CONSENT AND ADHERENCE.  CURRENT RECREATIONAL DRUG ABUSE.  AGGRESSIVE RECURRENT NATIVE KIDNEY DISEASE.  PRIMARY OXALOSIS
  • 23. Elements of Securing Informed Consent • Ensuring the participant’s understanding of the procedure & sequelae. • Confirming the participant’s medical & psychological suitability. • Educating the donor. • Ensuring the absence of coercion and free choice. • Documenting informed consent.
  • 24. Mansoura Policy ‫عائلتها‬ ‫أفراد‬ ‫ألحد‬ ‫زوجة‬ ‫تبرع‬ ‫حالة‬ ‫فى‬ ‫التب‬ ‫على‬ ‫الزوج‬ ‫وتوقيع‬ ‫موافقة‬ ‫يشترط‬‫رع‬
  • 25. CAN WE PREDICT RENAL TRANSPLANTATION OUTCOME?
  • 26. EQUATION BUILT FROM FRENCH DIVAT DATABASE VALIDATED ON UNOS DATABASE
  • 27. 41-50 31-40 <=30 >50 Recipient age Donor age Haplotype Time to diuresis Total steroid dose Immunosuppression ATN Number of acute rejection Points Total Points 5-Year graft survival Prob 21-30 31-40 >50 <=20 41-50 One haplotype MM(R) HLA-identical sibling Two haplotype MM(R+UR) Immediate Delayed <5 gm 5-10 gm >10 gm FK Rapa Aza CsA Triple No Yes No rejection One rejection More than one rejection 0 50 100 150 200 250 300 350 0.95 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0 10 20 30 40 50 60 70 80 90 100 Total points: 4060100115210220 COX REGRESSION BASED NOMOGRAM
  • 28. 41-50 31-40 <=30 >50Recipient age Donor age Haplotype Time to diuresis Total steroid dose Immunosuppression ATN Number of acute rejection Points Total Points 1-Year graft survival Prob 2-Year graft survival Prob 3-Year graft survival Prob 4-Year graft survival Prob 5-Year graft survival Prob 21-30 31-40 >50 <=20 41-50 One haplotype MM(R) HLA-identical sibling Two haplotype MM(R+UR) Immediate Delayed <5 gm 5-10 gm >10 gm FK Rapa Aza CsA Triple No Yes No rejection One rejection More than one rejection 0 50 100 150 200 250 300 350 0.95 0.9 0.8 0.7 0.95 0.9 0.8 0.7 0.6 0.95 0.9 0.8 0.7 0.6 0.5 0.95 0.9 0.8 0.7 0.6 0.5 0.4 0.95 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0 10 20 30 40 50 60 70 80 90 100 Akl et al., Exp Clin Transplant, 2008 COX REGRESSION BASED NOMOGRAM