strict monitoring of isoagg. 65 - chloe couat.pdf · abo system discovered in 1900 defined by three...
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Strict monitoring of isoagglutinins levels is required for
ABO-incompatible living-donor kidney transplantation
Ms. C.COUAT
Department of Nephrology and Organ Transplantation
Toulouse University Hospital (France)
(Pr.N.KAMAR)
INTRODUCTION
Today: many patients still die because of a shortage in kidney transplants
In 2011, the French bioethics laws were modified and allowed the use of kidney-transplant from most potential living donors (friends, couples…)
Issue: HLA and/or ABO incompatibilities between donors and recipients
Solution: pre-operative desensitization therapy
ABO System
Discovered in 1900
Defined by three letters according to the four blood types: A, B, O, and AB
A blood type is defined by the presence of antigens on the surface of red blood
cells (RBCs) and of circulating antibodies that are not present on the RBCs, called
isoagglutinins (anti-A and anti-B)
The rules for compatibility are the same as for blood transfusion
ABO system
BLOOD TYPE ANTIGENS ON
RBC’SURFACE
ANTIBODIES
PRESENT IN
THE SERUM
AB A+B Ø
A A B
B B A
O Ø A+B
In practice
Objective? Have the best immunological conditions at transplantation
How? with specific pre-transplant desensitization protocol to limit the risk of (hyper) acute rejection
In the case of ABO-incompatibility, the desensitization protocol is defined according to the baseline pre-transplant isoagglutinin level
These levels are monitored before and after transplantation, and thereafter according of a strict monitoring protocol.
In practice (2)
Analysis method: different dilution titrations :1; ½; ¼; 1/8; 1/16 or 1; 1/5. 1/10; …
Objective: isoagglutinin level closest to 1
Target level at transplantation: < 1/8
If isoagglutinin level remains > 1/16 at transplantation high risk of antibody-mediated rejection
If the target level is not reached, surgery can be postponed and desensitization protocol pursued
Techniques of desensitization:
Apheresis
Rituximab (Mabthera®)
Immunosuppressants
Techniques of desensitization: Apheresis
Extracorporeal purification which is implemented at the same time as hemodialysis (i.e. tandem procedure) on hemodialysis days (if the patient require dialysis)
This can be repeated over several session
Done over 2 to 5 hours at a low flow rate to achieve the best hemodynamic tolerance
Can be realized using hemodialysis catheters or arterio-venous fistula, or a simple peripheral catheter if the patient has a good venous network
It is a more-time efficient method compared to other methods
Protocols of apheresis (pre-transplant)
ABREVIATIONS •DFPP: Double filtration plasmapheresis •SIA: Specific ImmunoAdsorption •SSIA: Semi-Specific ImmunoAdsorption
INCOMPATIBILITIES
ABO
ABO+HLA
LEVELS
LOW
HIGH
/
APHERESIS USED
DFPP+ or SIA
DFPP and SIA
SSIA
+SIA or DFPP
AVERAGE NUMBER OF
SESSIONS
7
15
Immunoadsorption
Techniques of desensitization: rituximab (Mabthera®)
Monoclonal antibody directed against B cells. It blocks antibodies production
Its effect is longer lasting than apheresis, i.e. several months
Techniques of desensitization: Immunosupressants
Induction therapy by RATG or anti-CD25 monoclonal antibodies
It is started 10-12 days before surgery
Triple therapy composed of :
Tacrolimus (Prograf®, Advagraf®),
Mycophenolic acid (Cellcept®, Myfortic®)
Steroids (Cortancyl®).
Desensitization : exemple of protocol (adapted Tyden)
Rituximab 375 mg/m²
Tacrolimus MMF
Corticosteroid
IA
Tran
spla
nta
tio
n
IA IA IA
D-30 D-10 D-6 D-5 D-2 D-1 In hospital Long term
Post Transplant Medical Monitoring
IA :immunoadsorption
Post operative monitoring protocol of isoagglutinins
: Isoagglutinins blood test KB : Kidney Biopsy
D1 D7 D15 D28
KB
D0
KB
M2
M3 M6 M9 M12
KB KB Depending on
evolution of
kidney function
The activity of Toulouse Organ Transplant Unit
Around 200 kidney transplantations/ year
Around 55 to 60 living donor kidney transplantations / year
Of these, 20% ABO incompatible and/or HLA incompatible
Patients Since March 2011, 59 ABOi kidney transplantations were performed in our center
59 cases :
49: ABO-incompatible
10: ABO+ HLA-incompatible
Five patients were not included in the analysis because of lack of sufficient follow-up. Hence, herein, we present the results of 54 patients
Recipients’ age : 46.8± 13.5 years
54 patients
4 transplant failures
1 vein thrombosis
1 patient initially presented with vein thrombosis (surgical treatment)
then thrombotic microangiopathy, successfully treated with
plasmapheresis (3 PE+ 4 SSIA) and Eculizumab. However, he subsequently
developed progressive chronic rejection (graft loss at 14 months)
1 patient: nephrocalcinosis ( after 7 months with 2 PE post transplant)
1 chronic rejection
ABO- incompatible kidney transplantations: Outcomes
Graft survival: 92.5%
ABO- incompatible kidney transplantations: Outcomes
0 1 2 3 4 50
20
40
60
80
100
Années
Su
rvie
gre
ffon
B
n=54 n=53 n=53 n=53 n=48 n=42 n=32 n=20 n=21
Kidney function
years
Gra
ft s
urv
ival
Acute rejection rate: 33%
ABO- incompatible kidney transplantations: Isoagglutinin outcomes
Time Isoagglutinin level
Day -30
D0
D5
D15
M1
1/16 (0-1/128)
½ (0-1/16)
½ (0-1/5)
½ (1-1/40)
½ (1-1/20)
ABO- incompatible kidney transplantations: Effect of the Isoagglutinin increase on acute rejection rate
Increase in isoagglutinin
(level)
(n=10)
No increase in
Isoagglutinin level
(n=44)
ABOi
ABOi HLAi
Acute rejection
Cellular acute rejection
Antibody-mediated rejection
Mixte acute rejection
6 (60%)
4 (40%)
5 (50%)
1 (10%)
4 (40%)
0
38 (86.4%)
6 (13.6%)
13 (29.5%)
6 (13.6%)
4 (9.09%)
3 (6.8%)
The increase of isoagglutinin level was defined as an increase of 2 titers (exemple from ¼ to 1/16)
Conclusion
ABO incompatible kidney transplantation is successful. However, the rate of acute rejection remains high and a strict monitoring of isoagglutinin levels is required
Until February 2016, bothe naturel and immun isoagglutins were measured and no difference was made between both.
Actually, we are measuring both. This may help to decrease the risk of acute rejection
Acknowledgements
Pr N.Kamar 1,2,3
Dr A.Allal 1
Mrs C. Leroux-Biben 1
1 Department of Nephrology and Organ Transplantation Toulouse University Hospital
2Université Paul Sabitier (Toulouse, France)
3 INSERM U1043, IFR–BMT, CHU Purpan, Toulouse, France