Ways to improve the donor pool
- living donor programme
- ABO-HLA incompatible graft
- dual transplant
- paired kidney exchange
measurable renal transplant outcome
- graft survival
- graft function
- patient survival
Factors influencing graft survival
**1. Delayed graft function
2. HLA matching
3. HLA antibody – DSA **
- risk of ABMR **
**4. Timing of transplant **
pre-emptive > on dialysis
5. donor factor
- donor’s age
- living > deceased
- after brain death > after cardiac death
- Cold Ischaemic Time > 18hrs
- degree of proteinuria
6. recipient factor
- age (> 65 y/o - more comorbid)
- race (Caucasian > black)
- Obese + co-morbids
- primary disease: risk of recurrence
**7. rejection episode **
8. no of prev transplant
MHC = HLA
MHC I:
- all nucleated cells
- CD8
- HLA -A/B/C
**MHC II **
- mononuclear cells (macrophages / lymphocytes)
- CD 4
- HLA-D (DP / DQ / DR) – DR2 / DR3 / DR4
MHC III
DSA
Donor Specific anti HLA antibodies
Causes to develop DSA
- pregnancy
- Blood transfusion
- prev transplant
- donor relationship
- son/ daughter – mother
- husband – wife - Viral / bact infection (rare)
screening for HLA antibodies
& interpretations
a. solid based assay -
-solid phase assay –ELISA / flow cytometer (PRA / DSA)
-CDC technique –>20% cell lysis= +ve
b. cell based assay - HLA cross match (T/B cell flow cross match)
interpret cross-match result
T cell: HLA 1
B cells : HLA 1/2
PRA = panel reactive antibody
definition
measure specific ab (recipient) againts HLA ag panel (donor)
presence of antibodies in the recipient blood againts a panel of selected HLA antigen (represent donor population)
PRA > 10% = sensitized recipient
> 85% = highly sensitized
transplant compatibility
- ABO
- HLA
- anti-HLA antibodies
- donor characteristic
- recipient characteristic
ways of recognition of transplanted HLA by recipient T cells
A. direct pathways
- donor APC + CD8
- acute cell mediated rejection
B. indirect pathways
-host APC engulfed the donor cells + CD4
- chronic graft damage
Finally leads to initiation of immune response
initiation of immune response – binding of T cell + APC
- Signal 1:
- increase cal – activate calcineurin – IL2 release (must +signal2) - Signal 2: **(co-stimulation) **– activate tyroxine kinase + signal 1– IL2 release
- Signal 3: signal 1+2 - induce cytokine – clonal proliferation
Contraindications for recipient
**life expentancy < 5 years
- uncontrolled malignancy
- uncontrolled infection / chronic infection (HIV / hep C/ +ve HBeAg)
- systemic:
- DM with multiple TOD
- liver: cirrhosis / chronic active hepatitis
- heart: CCF < 35%/ diffuse dz / arrythmia / valvular / recent MI
-renal: * with caution (primary GN) / delayed 6-12month (SLE /HUS TTP / ANCA)
-stroke
-pulmonary dz - Psy pt
- Obese
- Substance abuse
- non-compliant
- > 60years
recipient evaluations
- immunological assessment
- ABO - cardiac evaluation
- respi assessment
- . thrombotic / bleeding assessment
- infection risk assessment
- malignancy assessment
- GI assessment
- GU assessment
- pelvic vasculature
- hematological assessment
- psychological assessment
warm ischemic time
period between circulatory arrest - beginning of cold storage
DBD > DCD
cold ischemic time
period of cold storage / machine perfusion
ideal < 12 hours
acceptable < 24 hours
rewarm time
period from the removal of the kidney from cold storage to reperfusion
perfusion machine :
flow rates > 100-150ml/min
vascular resistance 0.2-0.4
— better graft survival 4%
— delayed graft fx 6%
Kidney Allocation System in Malaysia
- MOSS (Malaysian Organ Sharing System; 1998)
- My KAS 1.0- 3.0 (2019)
Why change from MOSS to My KAS?
most of the criteria in MOSS is not implementable - due to logistic, human resources and funding
Allocation criteria in MOSS
- immunological: PRA + HLA matching
- waiting time
- logistic score
- recipient age
points of disussion
#1: lack of immunological services
#2: longer dialysis vintage, > cx
#3: prolonged ischemic time) esp for those in peninsular msia)
what you know about My KAS listing?
- using EPTS score
- My KAS 1.0 - 3.0
- EPTS > 20 not eligible (My KAS 1.0) then > 40% (in My KAS 2.0) not eligible
- lower the score, better survival
- PRA > 20% - not eligible (but now abolished PRA in my KAS 3.0)
- other criteria: dialysis vintage / ABO compatibility
what is the component of EPTS score?
- recipient age
- dialysis vintage
- DM
- previous transplant
What’s new in My KAS 4.0?
Active listing (NIC evaluation + pt’s consent to proceed with work out + clinical evaluation)
move away from EPTS
what’s difference in My KAS 3.0?
- abolish PRA
- clinical data by NIC
- complete vaccination + dental clearance
