1. A 39-year-old CKD 5 male, blood group B (Rh +ve) who received a kidney offer from his cousin who is blood group A2 (Rh – ve). The recipient anti-A IgG and IgM antibody titres are 1/2. 110 mismatch. There was no DSA.
-
- Will you go ahead?
- Any other invistigations required?
- If yes, what is your immunosuppression plan?
- If yes, do we need to monitor the anti-A antibody titre post-transplantation?
- If no, what are your other options?
Dear All
I have read your contributions, really impressed with your understanding of the ABOi transplantation.
Few questions here
1. Do we need to be aggressive with induction in this case, i.e to use ATG or even rituximab?
2. Regarding monitoring, do we need to be aggressive with monitoring given the fact it is a low-risk case, well-matched (assume the crossmatch is negative)?
We should not implement any protocol blindly, rather it has to be tailored to the index case
Excellent, well done.
1. Do we need to be aggressive with induction in this case, i.e to use ATG or even rituximab?
This case scenario has a living donor with 110 HLA mismatch and no DSA. I will consider the donor as ABO compatible (his blood group is A2, and the recipient’s anti-A IgG and IgM antibody titres are ½).
All these data suggest that the patient has a low immunological risk. Therefore, the induction with basiliximab can be acceptable for this case scenario based on the attached diagram (figure 1), which summarises the induction therapy choice based on risk assessment (1). Nevertheless, some centres will favour the induction with rATG-Thymoglobulin due to the associated lower risk of biopsy-proven acute rejection at one year, as illustrated in figure 2 (1).
In conclusion, for this scenario, both Basiliximab and ATG can be used based on the availability and local transplant centre protocol.
2. Regarding monitoring, do we need to be aggressive with monitoring given the fact it is a low-risk case, well-matched (assume the crossmatch is negative)?
I agree with my colleague Dr Mohammed Gafar that daily evaluation of the anti-A antibody titre post-transplantation is not mandatory. It may be reasonable only to collect blood samples that can be analysed later if allograft dysfunction occurs.
References:
1) John Vella, and Daniel C Brennan. Kidney transplantation in adults: Induction immunosuppressive therapy. © 2022 UpToDate. (Accessed on 27 April 2022).
figure 2. Approach to induction immunosuppressive therapy for HLA- and ABO-compatible kidney transplantation
Excellent, well done.
1. Do we need to be aggressive with induction in this case, i.e to use ATG or even rituximab?
Although blood group A2-incompatible transplantation is regarded as relatively low-risk,
significant rejection has been reported in some studies. many center use ATG not
rituximab(in those with low antibody titer less than 8).
Yorg AZZI et al A Safe Anti-A2 Titer for a Successful A2 Incompatible Kidney
Transplantation: ASingle-center Experience and Review of the Literature.Transplant
direct. 2021 Feb; 7(2): e662.
Gloor, James et al .ABO-incompatible kidney transplantation using both A2 and non-A2
living donors transplantation: Clinical transplant : April 15, 2003 – Volume 75 – Issue 7 – p
971-97.
. Regarding monitoring, do we need to be aggressive with monitoring given the fact it is a low-risk case, well-matched (assume the crossmatch is negative)?
Yes still monitoring is needed , A2 donor transplant is still ABOI even with low
risk but significant rejection has been reported.
Very good
1. No, we don’t need aggressive induction as minimal mismatch and recipient with B blood group and donor A2 can be considered as ABO compatible couple in addition No DSA, so basiliximab is enough
2. Close monitoring of iso agglutinin titer especially in 1st 2 weeks is better done as it is the most common time for AMR here.
To be honest , till now there is no fixed standard protocol for ABOi KX as there is no control study to differentiate strong and weak points of each protocol and every center depend on its own experience (local unit guidelines).
But here that patient low risk and no need for ATG better to give basiliximab.
Regarding titer monitoring:
Daily measurement of HLA or ABO antibody levels is not mandatory, but daily samples should be taken when in hospital and at each clinical visit and be available for urgent analysis if required. (1) .
References:
1-British Transplantation Society Guidelines.
A2 antigen is faintly expressed in the transplanted kidney, and usually the non A blood group recipient can safely accommodate the A2 transplanted kidney, and implementation for pre transplant desensitization protocol is not indicated, However high antibody titer might portend an increased risk of post transplant rejection and follow up of antibody titer post transplant is warranted, in particular for the first 2 weeks post transplant ,as it will be much less thereafter due to the phenomena of accommodation, which entail absence of evidence of rejection in the face of rising titer of anti A2 antibody. which is poorly explained. However, for how long and how frequent this antibody titer will be monitored thereafter is yet to be elucidated.
Similarly , the HLA mismatch is 110 with negative DSAs ,which indicate low risk for rejection, Class I HLA mismatch is associated with development of complement fixing DSAs with consequent AMR, however having no DSAs at the time of transplantation, reflect very low risk and preclude aggressive induction protocol with ATG. Nevertheless I would recommend follow up for the development of DSAs regularly , more frequently in the first 6 months, and less often thereafter. meanwhile, Tacrolimus based triple antirejection therapy {including MMF]is indicated with Basiliximab induction.
What does aggressive monitoring imply.
A less (aggressive) one might be wiser than waiting for a rise in chemistry which when detected would mean injury started earlier on.
The other way round when a rising titre is not accompanied by rising chemistry is presumably accommodation.
Contd to my previous comment:
Rise in titers 4-6 weeks post-transplant is not associated with any graft dysfunction, and hence not of any clinical significance.
Reference
Idian J Nephrology May-Jun 2017;27(3):195-198.
doi: 10.4103/0971-4065.202402.
1- rituximab is of choice, no need to be aggressive
2- no need to monitor
1. Do we need to be aggressive with induction in this case, i.e to use ATG or even rituximab?
This is a low-risk transplant (110 mismatch, no DSA, donor blood group A2 and anti A antibody tires 1:2).
No desensitization is required in this case.
Basiliximab induction with triple drug immunosuppression in form of Tacrolimus, MMF and steroids should suffice in this scenario.
Tailored immunosuppression, as used by Barnett et al is best option in ABO incompatible transplants.(1)
2. Regarding monitoring, do we need to be aggressive with monitoring given the fact it is a low-risk case, well-matched (assume the crossmatch is negative)?
This is a low-risk case, as the donor blood group is A2 and the baseline antibody titres are 1:2,pointing towards very low chances of rejection due to ABO incompatibility.
Nevertheless, it is wise to keep a tab on anti A antibody titres for first 3-4 weeks post-transplant as they are unpredictable and can increase leading to AMR. Rise in titres 4-6 weeks after transplant have no bearing on graft, hence no need to monitor them later.
Another strategy which can be utilized is to have close monitoring of graft function as worsening of graft function will point towards increasing titres, but I would be more comfortable monitoring the levels.
Reference:
1)Barnett AN, Manook M, Nagendran M, Kenchayikoppad S, Vaughan R, Dorling A, Hadjianastassiou VG, Mamode N. Tailored desensitization strategies in ABO blood group antibody incompatible renal transplantation. Transpl Int. 2014 Feb;27(2):187-96. doi: 10.1111/tri.12234. Epub 2013 Dec 28. PMID: 24188566.
Your last comment is correct because if you wait for the chemistry to rise this means injury started substantially earlier so in this early phase titre follow up is better.
This is a low-risk transplant recipient s with 0 DR mismatch, no DSA, negative crossmatch thus it is wise to give basiliximab and no benefit will be added with the use of ATG on the other hand higher rate of side effects may occur related to immunosuppression, pancytopenia
Because blood group A2 is less antigenic thus no aggressive monitoring is recommended, we can monitor only in the first 2 weeks which is the critical period before accommodation
very important point we should personalized the desensitization protocol and modified its use case by case based on the type and the titer of isoagglutinin value, presence of DSAs, in this scenario no need for induction with ATG, B cell depleting agent important part of the desensitization so still i preferred to use with lower dose of 200mg/m2 3-4 weeks prior to transplantation and the recent studies from local centers support the use of low dose Ritux even with out the need of cmv prophylaxis with low risk of infectious complications
regarding monitoring of ABs preferred to be more frequent in the first 2-4 week as the risk of AMR in the first two weeks post TX after the 4th week stable graft function even in the presence of ABS indicate graft accommodation.
References:
1- Kobayashi T. Editorial Comment to Low-dose rituximab induction therapy is effective in immunological high-risk renal transplantation without increasing cytomegalovirus infection. Int J Urol. 2020 Dec;27(12):1142-1143. doi: 10.1111/iju.14387. Epub 2020 Oct 3. PMID: 33012075.
1. Do we need to be aggressive with induction in this case, i.e to use ATG or even rituximab?
Giving the fact this a low risk patient with ABOi between B group and A2group(consider has low antigen effect)
Low titer of IgM antibodies 1/2)
Good HLA match 110 and no DSA
So no need for ATG or rituximab we can proceed with IL2 inhibitor and triple immunosuppressant (Tac,MMF and predinsilone as maintenance.
2. Regarding monitoring, do we need to be aggressive with monitoring given the fact it is a low-risk case, well-matched (assume the crossmatch is negative)?
Yes we should monitor the antibodies for the first month at least because this the time of AMR
1- No need to be aggressive, as it low immunological risk . Putting in our mind the risk of infection and malignancies with over immunosuppression.
2-her I need to be aggressive as it still ABOi RT and post transplant monitoring of rebound anti-A antibodies levels and the development of Denovo DSAs is mandatory as the risk of ABMR still high in this context.
ABOi transplantation is still risky. As the donor blood group is A2 blood, this is considered low risk but still, we need immune suppression by basiliximab or low dose ATG. we have to make sure that there is no DSA or any other risk. monitoring the anti A antibodies is reasonable, especially in the first two weeks. desensitization with rituximab here seems not essential in this case
Do we need to be aggressive with induction in this case, i.e to use ATG or even rituximab?
In a retrospective study that compares induction with basiliximab to induction with ATG in ABOi Tx, a higher rejection rate was found among the patients in the basiliximab group, while patient and graft survival, pathological findings in protocol biopsy at 1 year, graft function and complications were similar in both groups.
reference:
Del Bello A, Divard G, Belliere J, Congy‐Jolivet N, Lanfranco L, Ricard R, et al.Anti‐IL‐2R blockers comparing with polyclonal antibodies: Higher risk of rejection without negative mid‐term outcomes after ABO‐incompatible kidney transplantation. Clinical Transplantation. 2019;33:e13681.
Regarding monitoring, do we need to be aggressive with monitoring given the fact it is a low-risk case, well-matched (assume the crossmatch is negative)?
the titer of anti-ABO antibodies should be monitored after transplantation to detect any rebound in antibody production, which may indicate or induce AMR. usually, rebound happens in the first 2 weeks post-transplantation.
Reference:
Koo TY, Yang J. Current progress in ABO-incompatible kidney transplantation. Kidney Res Clin Pract 2015; 34: 170-179.
1aggresive induction is not neededis no DSA, NO positive crossmatch,low titre isoagglutinins, and he’s A2 donor which has low immunogenicity.
So basiliximab whould be agood and enough induction agent
2 Follow up is recommended during hospital stay and it’s better to e done till 2 weeks after that accommodation Occure and rebound increase in Ab will not harm the graft
Q1: There is no need for aggressive induction in this case because of low immunological risk.
Q2: Yes, there is need for sampling because of ABOi-TX.
1- No need for aggressive induction, just induction with Basiliximab + triple therapy (MMF + Steroids +Tacrolimus ) is sufficient due to low antigenicity of ABO A2 + No DSA
2- Monitoring is needed after 2 weeks as the routine of follow up for detection of high titer
So (early detection of predicted ABMR ) and early management
however is less to occur in this scenario
Aggressive induction by ATg or Rituximab or alemtuzumab is for high risk patients.
This ptn by definition is at risk but he is being of low immunological risk due to:
● He has 2 mismatches only in class 1 ( 110)
● He has no DSA
● His donar blood group is A2 that fortunately he has low antibody titre against it being anti A igG and IgM 1/2, but still is ABO incompatible.
Thus induction by basiliximab is better according to many centers.
What is against this is the possibility of ABMR within 1st 2 weeks or even acute rejection with 1st year , that is why some centers give ATG instead.
Question 2 regarding aggressive monitoring :
In the first 2 weeks it is better to do monitoring while being hospitalized that could be aggressive if there was any sign of rejection, clinical or lab wise being in the pre accomdodation peroid where there is a possibility acute rejection with ABMR specially in tbe 1st 2 weeks.
Daily or with longer interval peroid goes back to the local transplant center protocol.
After this peroid of 2 weeks of the accomodation phenomena; that one that is not fully understood where the high titres do not increase incidence of rejection, there will not be a need of follow up of the anti A antibodies’ titres unless there was clinical evidence of rejection
Considering his 1-1-0 HLA mismatch, I will use RTX as induction therapy to add further protection and guard against development of ABMR.
No need for aggressive monitoring, but to be monitored for antibody level after 2 weeks.
1) Will you go ahead?
Yes.
2) Any other invistigations required?
HLA typing, c PRA. Flow cytometry. MFI.
CMV, BKV PCR
3) If yes, what is your immunosuppression plan?
Basiliximab. Then Tacrolimus base immunosuppression
4) If yes, do we need to monitor the anti-A antibody titre post-transplantation?
Monitor serial DSA.
5) If no, what are your other options?
Pair kidney exchange program. Decease renal transplant.
Low risk patient no need for desensitisation
Basiliximab induction with immunosuppression tac, steroid and MMF
Yes, low immunological risk of A2 antigen , no DSA , good match
Investigations needed : FCXM / CDC
My immunosuppression plan?
Induction: Basiliximab + high dose IV steroids 500 mg for 2 days
Then, maintenance of triple therapy (steroid+ MMF +Tac )
monitor anti-A AB titer 2 weeks after RTX to predict early ABMR.
other options? PKD or waiting list for Cadaveric donors .
Will you go ahead?
I will proceed with this transplant, ABO is compatible, A2 incompatibility has low risk, DSA is negative and cross match of 110.
Any other investigations required?
I will need to do Flow-Cytometry cross match and CDC cross matching.
If yes, what is your immunosuppression plan?
This is considered low-risk and no desensitisation is required, for that I will go with standard immunosuppression, induction with Basiliximab and maintenance on triple immunosuppression.
If yes, do we need to monitor the anti-A antibody titre post-transplantation?
Yes I will monitor anti-A antibody titre in the first two weeks up to 3 months.
If no, what are your other options?
Paired-exchange donation program, or to be activated on transplant list for deceased renal transplant.
Will you go ahead?
Yes, I will go ahead. The case having low immunological risk with A2 kidney that carries no soluble ABO antigen and considered to be less immunogenic.
Any other invistigations required?
To fulfill the pe-transplant workup. CDCXM, FCXM and SAB
If yes, what is your immunosuppression plan?
In this case with 1-1-0 mismatch and donated kidney blood group A2; I will use RTX for induction because of HLA mismatch despite of the high rate of infection associated with RTX. RTX helps in prevention of rebound DSA.
for maintenance IS: TAC, MMF and Prednisolone.
If yes, do we need to monitor the anti-A antibody titre post-transplantation?
Considering the low immunological risk of ABOi in this case(as being a receiver of a kidney blood group A2) no need for daily monitoring of isoagglutinin post TX but to be performed at 1 to weeks to monitor for and guard against ABMR.
If no, what are your other options?
Other options are:
1. Kidney paired donation.
2. Waiting list for deceased donation.
3. Altruism.
* Will you go ahead?
Yes, I will go ahead because this patient
considered as low immunological risk, HLA mismatch 1_1_0, (excellent match)
No DSA
A2 blood group is less immunogenic than A1 and still with low titres 1:2
(A2 to B kidney transplantation does not adversely affect graft or patient survival. A2 to B kidney transplantation is a viable option for transplant centers to reduce the longest wait times for B blood group recipients) 1.
*Any other invistigations required?
Routine work up before transplantation
Crossmatch CDC/FCXM
* If yes, what is your immunosuppression plan?
No need for desensitization, he need
Induction therapy with Basiliximab and triple IS (tac, MMF, Steroid)
*(Basiliximab may be considered the drug of choice for the prophylaxis of acute rejection in standard renal transplant recipients). 2
* If yes, do we need to monitor the anti-A antibody titre post-transplantation?
A2 is less immunogenic than A1, but still immunogenic, so it need to monitor in the first weeks for the risk of AMR then when there is graft dysfunction.
If no, what are your other options?
Kidney paired donation program is other option.
References
(1)Shapiro, Ron1; Van Kluyve, Nicole1; Khaim, Rafael1; Geatrakas, Sara1A2 to b Renal Transplantation
One Center’s Experience and the Implications for Decreasing Wait Times and Reducing Racial Disparities in Organ Allocation. Transplantation: July 2018 – Volume 102 – Issue – p S476
(2) Ponticelli C. Basiliximab: efficacy and safety evaluation in kidney transplantation. Expert Opin Drug Saf. 2014 Mar;13(3):373-81. doi: 10.1517/14740338.2014.861816. Epub 2013 Nov 25. PMID: 24266670.
IMHO, i would proceed with transplantation as negative donor specific antibodies and A2 is low immunogenic
yes, FCXM,
should be dealt with as high risk kindey transplantation:
yes,
regular KFT testing
Will you go ahead?
Yes, it is a good renal transplant offer as donor blood group is A2 which is of very low immunogenicity with low anti A IgG and IgM titers, good mismatch 110, and absence of DSA.
Any other investigations required?
crossmatch
If yes, what is your immunosuppression plan?
Low/standard risk protocol
Induction: basiliximab
Maintenance: CNI/steroids/MMF.
If yes, do we need to monitor the anti-A antibody titre post-transplantation?
No.
It is indicated if graft dysfunction plus DSA
If no, what are your other options?
Paired kidney exchange program or wait for another donor.
Few questions here
1. Do we need to be aggressive with induction in this case, i.e to use ATG or even rituximab?
This clinical scenario shows a low immunological risk transplant offer as mentioned earlier so there is no need for heavy induction with ATG or Rituximab.
2. Regarding monitoring, do we need to be aggressive with monitoring given the fact it is a low-risk case, well-matched (assume the crossmatch is negative)?
It is not needed unless there is graft dysfunction
We should not implement any protocol blindly, rather it has to be tailored to the index case
Q1
1- Will you go ahead
Yes , as blood group A2 is less immunogenic than A1 and B and many transplant centres as OPTN permitted transplanting A2 and A2B kidneys to blood group B recipient .
2- Other investigations :
CDC and flowcytometry crossmatch.
3- If yes , what’s the immunosuppression protocol?
a- Pretransplantation reduction of Abs level through either PE , DFPE or immuneadsorption.
b- B cell depletion with Rituximab .
c- Induction with r ATG followed by maintenance with triple IS ( Tac , MMF and steroid)
d- Regular monitoring of Anti B isoaggulitin Ab titre postoperative.
4- Other options
a- Paired kidney donation
b- Remain on waiting list for more suitable donor either living or deceased .
5- Do we need to monitor Ab postoperative?
Yes as rebound increase in Ab level is associated AMR .
Will you go ahead?
Any other invistigations required?
If yes, what is your immunosuppression plan?
If no, what are your other options?
There is a breach of academic integrity (a clear case of academic dishonesty). This reply was copied and pasted from another colleague. You are subject to investigation.
Manal Malik
24 days ago
☆Will you go ahead?
______________________
Yes, I will go ahead due to the following:
1-The donor blood group is A2:
Note: The ABO blood subgroup A2
expresses lower levels of A antigen on the
cell surface and is less immunogenic
toward anti-A immunoglobulin present in
blood type O or B recipients.
Some studies have shown successful
kidney transplantation from A2 donors
into O or B recipients with low pre-
transplant anti-A titers [1].
2- Low recipient IgG titers <1:8.
3- There is no DSA
4- Good HLA mismatche (1.1.0)
☆Are any other investigations required?
__________________________________________
CDC and Flowcytometric crossmatch.
☆If yes, what is your immunosuppression plan?
_____
Basiliximab induction and maintenance with Tacrolimus, prednisolone and MMF.
☆If yes, do we need to monitor the anti-A antibody titer post-transplantation?
_____________________________________
Yes, because attention should be paid to IgM titers
Some studies showed a high incidence of early acute rejection or thrombotic microangiopathy in A2 to O and B kidney transplants [1].
☆If not, what are your other options?
___________________________
-I will search for another donor with same blood group, wait for deceased donor or Kidney Paired Donation.
_______________________
Ref:
[1] Joshua Tierney et al.
Transplantation of ABO A2 kidneys into O recipients: do IgM anti-A1 titers matter?
Clin Transplant. 2015 Apr.
Yes , will go on with the transplantation , will ask for follow-up of the anti-body titre especially in the 1st 2 weeks post-transplantation.
check for de novo DSA post-transplantation.
Regarding immunosuppression :
induction therapy with Basilixumab( Simulect )
maintenance therapy with Tacrolimus + MMF + prednisolone.
Will you go ahead?
Yes due to the low antigenicity of ABO A2 antigens
living donor
No DSA
good matching ( Mismatch 110 )
Avoiding long waiting lists for dialysis
Are any other investigations required?
Flowcytometry cross match and CDC crossmatch
* If yes, what is your immunosuppression plan?
Induction: Basiliximab + high dose IV steroids
with the maintenance of triple therapy (steroid+ MMF + Tacrolimus )
* If yes, do we need to monitor the anti-A antibody titer post-transplantation?
Yes, Post-transplant after 2 weeks to detect high anti-A2 titer with early prediction of ABMR
* If not, what are your other options?
PKD
or staying on the waiting list for Deceased donors
Q1: Yes, I will perform the transplantation. Because of low immunological risk.
Q2: Doing CDXM and FCXM before TX is necessary.
Q3: There is no need for desensitization. Induction therapy with basiliximab and methylprednisolone is needed. Maintenance immunosuppression including tacrolimus, MMF and steroids as triple standard therapy is considered.
Q4: Monitoring of antibodies especially daily in the first two weeks and then 2-3 times a week for two weeks and then weekly until 3 month is preferred.
Q5: Kidney paired donation (KPD) and compatible deceased donor are another alternative options.
Will you go ahead?
Yes, I will go ahead for the transplant
Pre transplant CDC cross match is needed
Basiliximab on day 1 and day 4 with triple immunosupression
Yes we still need to monitor after 2-3 weeks
If no, what are your other option?
We don’t have Paired exchange program which is the appropriate program so we consider waiting list and to continue renal replacement therapy .
Yes, because de titres of anti-A are very low, and ABOi kidney transplantation with A2 organs has been accomplished with standard immunosuppressive therapy without any additional measures.
As the patient still had 110 mismatch, I would like to do an HLA flow cytometry to evaluate epitopes, which may be much worse than expected.
Induction – basiliximabe + Triple standard immunosuppression – CNI, MMFI, corticosteroid.
No, because monitoring is only needed in cases of desensitization.
Will you go ahead?
Yes , as there is low immunological risk with blood group A2 donor due to less antigen expressed in the graft tissue.anti-A antibody titter is 1/2 in the recipient which is low and HLA mismatch is 110 with no DSA.
Any other invistigations required?
CDC and FCXM
If yes, what is your immunosuppression plan?
I will use the standard immunosuppressant protocol by using basiliximab in a dose of 20 mg in day 0 and day 4 and maintenance by using the triple immunosuppressant drugs (Tacrollimus, MMF and PRD)
If yes, do we need to monitor the anti-A antibody titre post-transplantation?
Yes .as it still ABOi RT we need to monitor at least for the first 2 weeks as after that accommodation will ensue.
If no, what are your other options?
-wait for deseased donor
-enrolled in PKD program
_Will you go ahead?
Yes, with standard immunological risk as anti-A antibody titer is 1:2, blood group A2 donors are not highly immunogenic with low expression of blood group antigens and no DSA and 110 mismatch
-Any other investigations required?
FCXM
-If yes, what is your immunosuppression plan?
Desensitization is not needed as the anti-A antibody titer is low. .So ,induction with Basiliximab could be fair with triple maintenance immunosuppression with tacrolimus, MMF and steroids.
-If yes, do we need to monitor the anti-A antibody titre post-transplantation?
Yes, for detection of possible rebound in serum antibody production.
_If no, what are your other options?
There is kidney paired donation or deceased donor transplant
Will you go ahead?
Yes , I will proceed as A2 is low antigenic.
also antibodies titer less than 1/8
The donor is living
Accepted Mismatch
Are any other investigations required?
Cross matching (CDC , flowcytometry)
* If yes, what is your immunosuppression plan?
No need for desensitization as titer less than 8
Induction: Basiliximab
with the maintenance of triple therapy (steroid+ MMF + Tacrolimus )
* If yes, do we need to monitor the anti-A antibody titer post-transplantation?
Yes, antibody titer must be followed in the first few weeks 2-4 weeks to monitor rebound to guard against ABMR
* If not, what are your other options?
PKD
1) keep on dialysis and wait for a deceased donor
2) enroll in KPD program
1.Yes, i will go for kidney trasnplantation….Since A2 is less immunogenic compared to other blood group and also pre transplant titre is very low.Rh antigen is not expressed on endothelial cells of kidney..so It is not a point of concern if donor is Rh negative and receipient is Rh positive.Also There is no problem of DSA in this transplant ..so.i will go ahead with transplant.
.2. Though DSA is negative..crossmatch should be done in this case. . 3.I will go with Basiliximab induction..2 doses of 20 mg on day 1 and day 4….with standard triple immunosuppression of tacrolimnus, mmf and steroid.I will not use ATG in this case since in Aboi transplant infections there is increase chance of viral infection cytomegalovirus ..BK virus which contribute to increased mortality of ABO i transplant compared to ABO c transplant.with ATG specially there are high risk of cytomegalovirus virus infection. Also this transplant is of low immunological risk..so No need to intense immunosuppression. . 4.Its better to monitor Titre for 2 weeks…But if we are living in resorce limited country/patient is poor ..we may choose not to monitor ,because there is less chance that antibody titre will increase post transplant. . 5. Kidney pain donation is next best option.After kidney pair donation next best will be deceased kidney donation
1-Will you go ahead?
ABO incompatible .The donor caries A2 blood group ,which is les immunogenic and the recipient has a low eligible titre of anti –A antibodies. In the absence of DSA and HLA mismatches of 110 ,this recipient has a low immunological risk and accordingly I will go ahead for transplantation .
2-Any other invistigations required?
CDC cross match
3-If yes, what is your immunosuppression plan?
Induction with basilixmab and maintenance triple TAC
4-If yes, do we need to monitor the anti-A antibody titre post-transplantation?
Yes , specially during the first 2 weeks
5-If no, what are your other options?
-Paired kidney transplant
-deceased donor kidney transplant
Reference
Yorg Azzi et al. A Safe Anti-A2 Titer for a Successful A2 Incompatible Kidney Transplantation: A Single-center Experience and Review of the Literature. Transplant Direct. 2021 Feb; 7(2): e662.
Blood group A2 donors are less likely to have AMR(weak and less expressed A2 antigen) in ABOi-KT.
Post-transplant antibody titer should be closely followed especially in the first 2 weeks post-transplant.
As in tailored desensitization strategy no need for aggressive preoperative treatment(low antibody titer)
Current protocols and outcomes of ABOi-KT Article…World Journal of Transplantation 2020
yes, we can go ahead (it is considered ABO compatible less immunogenic risk, no DSA, low anti a titers … acceptable for transplantation).
flow cytometry cross match.
no need for desensitization in such case ,induction would be by basiliximab (20 mg for each day zero and day 4), and triple immunosuppressive regimen ( better to be tacrolimus ,MMF, and corticosteroids).
in my opinion , I think it is not mandatory unless a rejection episode is suspected and to be managed mainly by plasmapheresis.
other options may include kidney paired donation program or deceased donor plus a trial for desensitization may be considered before if the antibody titers are elevated .
Will you go ahead?
1- the donor is a live one.
2- this mismatch is low, 110.
3- the recipient has no DSA.
Any other invistigations required?
If yes, what is your immunosuppression plan?
If yes, do we need to monitor the anti-A antibody titre post-transplantation?
If no, what are your other options?
Yes will go ahead
A2 consider as low immunological risk but it’s still part from ABOI and few patients with A2 antibodies may develop AMR
patient need to rituximab therapy for depletion of B cell or basiliximab
no need for aggressive monitoring to anti A antibody daily
it’s need weekly monitoring to avoid AMR
If no another option like PKD less expensive and complications
yes, with standard immunological risk as anti-A antibody titer is 1:2 and organs from blood group A2 donors are less immunogenic due to low expression of blood group antigens.
the patient has no DSA and 110 mismatch
Flowcytometry crossmatch should be done
No need for desensitization as the anti-A antibody titer is low
Induction with Basiliximab (standard immunological risk)
Triple maintenance immunosuppression with tacrolimus, MMF and steroids.
Yes, to detect rebound in serum antibody production.
Kidney paired donation
Deceased donor transplant
Morath C, Zeier M, Döhler B, Opelz G and Süsal C (2017) ABO-Incompatible Kidney Transplantation. Front. Immunol. 8:234
Good plan
Very good
Will you go ahead?
-Yes, I will go ahead, the donor blood group is A2 which is a low immunogenic blood group with anti-A IgG and IgM antibody titers are ½ ( accept titer ˂1/8 in the most centers). There are no DSA and HLA mismatches 1.1.0.
Are any other investigations required?
Crossmatch CDC and FCXM
If yes, what is your immunosuppression plan?
Induction with basiliximab and maintenance immunosuppression Tac , MMF, and prednisolone.
If yes, do we need to monitor the anti-A antibody titer post-transplantation?
Yes, especially in the first 2 weeks and then according to follow-up.
If not, what are your other options?
-Search for another donor
-deceased donor.
– Kidney Paired Donation
Very good
Will you go ahead?
Here HLA match is good i.e. 1 I 0 , Less immunogenic blood group of Donor- A2, Absent DSA and low antibody titre 1/2 making it a low risk case. I will go ahead with transplantation.
Any other investigations required?
CDC cross match- It should be negative.
If yes, what is your immunosuppression plan?
As it is low risk case , so will start induction with Basiliximab and maintenance triple immunosuppression with Tacrolimus, MMF and prednisolone.
If yes, do we need to monitor the anti-A antibody titre post-transplantation?
As A2 is less immunogenic routine antibody monitoring is not required. I will still check antibody titre around 2 week to identify any rejection and start timely treatment. After that process of accommodation will start.
If no, what are your other options?
Enrol in paired kidney donation programme or deceased donor allocation system.
Wait for compatible donor and stay on dialysis
Reference
Yorg Azzi et al. A Safe Anti-A2 Titer for a Successful A2 Incompatible Kidney Transplantation: A Single-center Experience and Review of the Literature. Transplant Direct. 2021 Feb; 7(2): e662.
Definitely you will need monitoring!
A1- yes, I will proceed with the transplantation and I will consider him a low immunological risk. no desensitization needed
A2- FCXM
A3- induction with Basiliximab, methylprednisolone
maintenance with tacrolimus + MMF + steroid started 2 days before surgery
A4- yes, I will monitor them post-transplantation
A5-
paired kidney donation
Deceased donor
Very good
-I will proceed since this is a living related donor with strong HLA matching (110 mismatches), no DSAs, and no DSAs present.
When it comes to blood groups,
Patients with anti-A2 titers less than 1/8 (but this is different from centre to centre)are safe candidates for A2-incompatible transplantation, and their short-term kidney allograft results are favourable. A2 is less immunogenic.
Is there anything more that needs to be done?
CDC and FXCM with a mean channel shift of less than 250 to proceed safely.
If you answered yes, what is your immunosuppressive strategy?
Because of the risk of antibodies rebounding after transplantation, daily monitoring in the first two weeks is preferred, followed by three times a week for another two weeks, and then weekly until three months. I will prefer ATG induction and triple immunosuppressant (tacrolimus, MMF, prednisolone). If high creatinine at any time, repeat cross match and renal biopsy.
If this is the case, what are your alternative options?
Kidney paired donation, or wait for DD with compatible ABO.
Loarte-Campos P, Ajaimy M, Graham J, Liriano-Ward L, Pynadath C, Uehlinger J, Parides M, Campbell A, Colovai A, Alani O, Le M, Greenstein S, Kinkhabwala M, Rocca J, Akalin E.
Thank you, Dr Weam,
Well presented, but I disagree with ATG
induction since it is a very low risk regarding the ABO antigen and also HLA
antigens. Just basiliximab induction would be enough.
Will you go ahead؟
Yes.AS A 2 has lower immunological risk , donor A2 kidneys can generally transplanted
recipients with low pretransplant anti-A titers without the use of desensitization .
Final crossmatch ,FCXM.
If yes, what is your immunosuppression plan?
Induction immunosuppressive with rATG-Thymoglobulin .
Maintenance immunosuppression regimen that includes CNI(TAC) an antimetabolite
(MMF), and Prednisolone.
As incompatible recipient antibodies need to be monitored post transplant.
Wait suitable donor.
PKD
Or DDA.
Thank you, Dr Mohamed,
Well presented, but I disagree with ATG
induction since it is a very low risk regarding the ABO antigen and also HLA
antigens. Just basiliximab induction would be enough.
In the meantime, ABOi kidney transplantation has become a routine procedure through Desensitization which usually achieved by apheresis and B cell-depleting therapies that are accompanied by powerful immunosuppression. Anti-A/B antibodies are aimed to be below a certain threshold that is considered to be safe (e.g., <1:32 in tube technique) at the time of transplantation and during the first 2 weeks after surgery.
1. We can go ahead without desensitization due to many factors which encouraging us
A. acceptable HLA matching (110 mismatch)
B. No DSAs.
C. Blood group A2-to blood group B transplantation is acceptable because-A2 is low immunogenic with low titers ½
2 ▪︎Any other investigations required?
CDC XM ,FCXM
3. Immunosuppression plan (consider the patient as high risk)
Induction by ATG maintenance by TAC, MMF, Steroid
4-After the ABO incompatible transplant the level of anti-ABO antibody titer must be monitored to detect rebound in the serum antibody production.
5.other options
1-looking for another suitable donor.
2.Kidney paired donation
3.Deseased donor
Ref:
1.ABO-Incompatible Kidney Transplantation
Christian Morath,1,* Martin Zeier,1 Bernd Döhler,2 Gerhard Opelz,2 and Caner Süsal2
2. -Lecture of Abubaker Hassan, MD, FRCPC Associate Professor
Saskatchewan Transplant Program University of Saskatchewan
Thank you, Dr Manal,
Well presented, but I disagree with ATG
induction since it is a very low risk regarding the ABO antigen and also HLA
antigens. Just basiliximab induction would be enough.
Excellent response. Any one thinking of ATG induction? Please justify your response
ATG is the another option for induction with Basiliximab although some studies shown that ABO-I kidney transplant maintained on tacrolimus, mycophenolate mofetil, and steroids have lower acute rejection rates when using ATG induction therapy compared to using basiliximab induction therapy(1) (2).
On the other hand, other studies suggested that IL-2 RA induction therapy involving basiliximab eliminates the need for steroid maintenance therapy while providing effective induction of immunosuppression in ABO-I kidney transplant recipients(3).
In this patient with low immunological risk(matching 4/6 with DSA negative) better to use basiliximab other than ATG.
References:
1-Mohamed M, Sweeney T, Alkhader D, Nassar M, Alqassieh A, Lakhdar S, Nso N, Fülöp T, Daoud A, Soliman KM. ABO incompatibility in renal transplantation. World J Transplant 2021; 11(9): 388-399 [PMID: 34631470 DOI: 10.5500/wjt.v11.i9.388].
2- de Weerd AE, Betjes MGH. ABO-Incompatible Kidney Transplant Outcomes. Clin J Am Soc Nephrol. 2018;13:1234-1243. [PubMed] .
3-Ando T, Tojimbara T, Sato S, Nakamura M, Kawase T, Kai K, Nakajima I, Fuchinoue S, Teraoka S. Efficacy of basiliximab induction therapy in ABO-incompatible kidney transplantation: a rapid steroid withdrawal protocol. Transplant Proc. 2004;36:2182-2183. [PubMed]
Thank you, Dr Mohamed,
Thank you for the effort. I disagree with ATG
induction since it is a very low risk regarding the ABO antigen and also HLA
antigens. Just basiliximab induction would be enough.
ATG has been used as an induction therapy in ABO incompatible renal transplants. ATG induction has shown to have less rejection episodes than IL-2 receptor antibody induction. (1,2)
The Mayo clinic group in USA uses ATG as induction agent in their protocol for ABO incompatible transplant. (3)
References:
1) de Weerd AE, Betjes MGH. ABO-Incompatible Kidney Transplant Outcomes: A Meta-Analysis. Clin J Am Soc Nephrol. 2018 Aug 7;13(8):1234-1243. doi: 10.2215/CJN.00540118. Epub 2018 Jul 16. PMID: 30012630; PMCID: PMC6086717.
2) Mohamed M, Sweeney T, Alkhader D, Nassar M, Alqassieh A, Lakhdar S, Nso N, Fülöp T, Daoud A, Soliman KM. ABO incompatibility in renal transplantation. World J Transplant. 2021 Sep 18;11(9):388-399. doi: 10.5500/wjt.v11.i9.388. PMID: 34631470; PMCID: PMC8465511.
3) Koo TY, Yang J. Current progress in ABO-incompatible kidney transplantation. Kidney Res Clin Pract. 2015 Sep;34(3):170-9. doi: 10.1016/j.krcp.2015.08.005. Epub 2015 Aug 20. PMID: 26484043; PMCID: PMC4608875.
Thank you, Amit
Can you justify the ATG induction? Since it is a very low risk regarding the ABO antigen and also HLA antigens. Just basiliximab induction would be enough.
Thank you Sir.
In my answer to the scenario, I have mentioned to use Basiliximab as induction.
As this is a low-risk transplant (110 mismatch, no DSA, donor blood group A2 and anti A antibody tires 1:2), no desensitization is required.
Basiliximab induction with triple drug immunosuppression in form of Tacrolimus, MMF and steroids should suffice in this scenario.
The answer written above (regarding ATG use is with reference to the question asked by Dr Ala Ali regarding the use of ATG in ABO incompatible transplants.
In a retrospective study that compares induction with basiliximab to induction with ATG in ABOi Tx, a higher rejection rate was found among the patients in the basiliximab group, while patient and graft survival, pathological findings in protocol biopsy at 1 year, graft function and complications were similar in both groups.
reference:
Del Bello A, Divard G, Belliere J, Congy‐Jolivet N, Lanfranco L, Ricard R, et al.Anti‐IL‐2R blockers comparing with polyclonal antibodies: Higher risk of rejection without negative mid‐term outcomes after ABO‐incompatible kidney transplantation. Clinical Transplantation. 2019;33:e13681
yorg Azzi, MD, Gayatri Nair,et Al.Safe Anti-A2 Titer for a Successful A2 Incompatible Kidney Transplantation: A Single-center Experience and Review of the Literature.Transplant Direct. 2021 Feb; 7(2): e662.
Agree. Thank you
1. A 39-year-old CKD 5 male, blood group B (Rh +ve) who received a kidney offer from his cousin who is blood group A2 (Rh – ve). The recipient anti-A IgG and IgM antibody titres are 1/2. 110 mismatch. There was no DSA.
Will you go ahead?
Yes.
A2 to B kidney transplantation is a viable option to reduce the longest wait times for B blood group recipients.
A titer of 8 or below is used by many centers, based on the report by Welsh et al.
For A2 grafts, a higher titer seems to be safe.
================================================
Any other investigations required?
Clinical evaluation of recipient & donor according to standard national guidelines.
A second, confirmatory subtype test.
Titers should be confirmed to be 1 in 8 or less within 24 hours prior to transplantation.
.===============================================
If yes, what is your immunosuppression plan?
IS would consists of Tac, MMF & prednisolone.
Induction would be according to local centre’s protocol, basiliximab would be the preferred choice here.
================================================
If yes, do we need to monitor the anti-A antibody titre post-transplantation?
Titre measured on days 1, 3, 5,7 & 10 post-transplant.
A significant (2 or more dilutions) rise in titres should prompt concern.
A rise in creatinine together with a rise in titres would indicate the need for an immediate biopsy followed by PP or IA as necessary.
A third of recipients will have a titre rise with no graft dysfunction.
================================================
If no, what are your other options?
PKD
Combined PKD& Desensitization
Wait for DD transplant
References
1.KAG (18)36 Transplanting blood group incompatible kidneys: potential utilisation of A2 donors
N Mamode, M Manook, T Maggs, J Galliford, S Ball, J White, L Mumford
2.Gunnela Nordén and Michael E. Breimer ABO-Incompatible Kidney Transplantation: Overview and New Strategies Trends in Transplantation 2007;1:61-68
Thank you, Agree
Will you go ahead?
Yes, I will. A2 is a low immunogenic blood group and he has low titer (1/2)
Any other investigations required?
FCXM and CDC
Flow cytometry antiIgM and antiIgG
If yes, what is your immunosuppression plan?
rATG for induction, and maintenance with Tacrolimus, MMF, and Steroids.
If yes, do we need to monitor the anti-A antibody titer post-transplantation?
Yes, it is advisable to do scheduled monitoring of DSA levels, even with low initial titration levels
If no, what are your other options?
Paired exchange program
Or still wait for a better compatible deceased donor transplant
Thank you, Filipe,
I disagree with ATG induction since it is a very low risk regarding the ABO antigen and also HLA antigens. Just basiliximab induction would be enough.
1-Yes I will go ahead with the Transplanation as A2 kidney has low immunogenicity and Ab titer is <1/2 with HLA mismatch 110 and No DSA
2- Flowcytometery
3- Since Ab titer is ,<1/8 desensitization is not needed and induction with IL 2 receptor
antagonist Basiliximab and maintenance with Tac , MMF , prednisolone
4-It is not needed to monitor the Ab titer post transplantation with this data but if any complication occurred or with graft dysfunction it can be monitored.
5- Other options are Paired kidney exchange program or waiting for a compatible donor
Yes, agree, well done
Blood group A divided into A1 & A2. A2 has very low immunogenicity because it has very low low expression or not exist in renal tubules & glomerular epithelium.
References:
Azzi Y., Nair G., Loarte-Campos P., Ajaimy M. et al. A Safe Anti-A2 Titer for a Successful A2 Incompatible Kidney Transplantation: A Single-center Experience and Review of the Literature. TransplantDirect, 2021.
Yes, agree, well done
Case scenario I
A 39-year-old CKD 5 male, blood group B (Rh +ve) who received a kidney offer from his cousin who is blood group A2 (Rh – ve). The recipient anti-A IgG and IgM antibody titres are 1/2. 110 mismatch. There was no DSA.
Will you go ahead?
Yes, I will. A2 is low immunogenic blood group and he has low titer <1:8
Any other investigations required?
FCXM
If yes, what is your immunosuppression plan?
Basiliximab for induction, maintenance with Tacrolimus, MMF and Steroids.
If yes, do we need to monitor the anti-A antibody titer post-transplantation?
It is controversial, although the patient has low anti isoagglutinin titer 1:2 and the donor is A2 (with very low immunogenicity) it would be wise to monitor anti-A Ab titer post-transplant
If no, what are your other options?
Paired exchange program
KAS, keeping in mind the results of ABOi living donor KT has better outcome than deceased donor transplant
Yes, agree, well done
1.Yes I will go ahead with transplant.
2.CDC crossmatch to be done.
Routine donor and recipient workup to be
done.
Get an idea about native kidney disease which
runs in family.
3.I will go with no rtx and plasmaexchange as
A2 titre is low.
ATG 3mg/kg induction with triple
maintainance immunosuppression.
4.No need to monitor anti-A titre post tx.
5.kidney paired donation.
Thank you, Kumar
I disagree with ATG induction since it is a very low risk regarding the ABO antigen and also HLA antigens. Just basiliximab induction would be enough. Can you justify the use of ATG?
Yes, I will.
CDC crossmatching, FCXM
A2 is of low immunogenicity, and the anti A antibody titer is low, with 110 mismatch, no DSA, So this is a low-risk transplant, no desensitization is required, induction with basiliximab and maintenance treatment with Tac, MMF, and steroid.
yes, follow up for anti A antibody in the first 3-4 weeks post-transplant is prefered.
we can list him for paired kidney donation or deceased donor program.
Reference:
Yorg Azzi, MD, Gayatri Nair,et Al.Safe Anti-A2 Titer for a Successful A2 Incompatible Kidney Transplantation: A Single-center Experience and Review of the Literature.Transplant Direct. 2021 Feb; 7(2): e662.
Excellent
thank you
1-Antigenic expression of A2 is quantitatively and qualitatively less than that of A1
Immunogenic risk based on antigen expression alone is A1>B>A2
The initial titer of the anti-A or B antibody, rather than the antigen targeted (A1, A2, or B), was initially reported to correlate with the risk of AMR in such cases
Goal of isoagglutinin titer to prevent hyperacute rejection is variable across transplantation centers, ranging from ≤ 1:4 to ≤ 1:32 before transplantation
So,we can preced the transplantion because of low anti-A IgG and IgM antibody titres are ½ without desensitization
2-crossmatch(FCXM)
DSA Titer
3-110 mismatch.
2 HLA mismatch so the patient considered as high risk
Induction by ATG
Maintenance by TAG,MMF,Steroid
4-After the ABO incompatible transplant necessitating initiation of antibody-depletion procedures, the level of anti-ABO antibody titer must be monitored to detect rebound in the serum antibody production.
Monitoring done daily post transplant until patient discharged from hospital then two to three times per week for the first month posttransplant, then weekly for the 2nd and 3rd month posttransplant, and then done annually
5-If we refuse this donor we should wait for another suitable donor or do (KIDNEY PAIRED DONATION)
Reference
1-Masaki Muramatsu, Hector Daniel Gonzalez, Roberto Cacciola, Atsushi Aikawa, Magdi M Yaqoob, and Carmelo Puliatti. ABO incompatible renal transplants: Good or bad?. World J Transplant. 2014 Mar 24; 4(1): 18–29.
Published online 2014 Mar 24. doi: 10.5500/wjt.v4.i1.18.
2-Up to date
3-Lecture of Abubaker Hassan, MD, FRCPC Associate Professor
Saskatchewan Transplant Program University of Saskatchewan
Thank you, Dalia
I disagree with ATG induction since it is a very low risk regarding the ABO antigen and also HLA antigens. Just basiliximab induction would be enough. Can you justify the use of ATG?
Will you go ahead?
Yes, will go ahead with the transplant as A2 incompatible kidney transplant with low immunological risk (tow mismatch and negative DSA), blood group B permitted to accept kidney from A2 minor Donor group with weak antigenicity compared to the major donor group of A1.
Any other investigations required?
FXCM with mean channel shift < 250, PRA %
If yes, what is your immunosuppression plan?
No desensitization required for A2/A2B incompatible kidney transplantation with given low titer of antiA2 IgG, IgM < 16 (1).
Induction with basilixamab 20mg, D0, D4, triple maintenance IS including Tacrolimus, MMF 1gm BID prednisolone , references from some centers they use low dose ATG 1.5mg /kg for total 4 doses followed by triple maintenance IS preferred to be started 14 days prior to transplantation.
If yes, do we need to monitor the anti-A antibody titer post-transplantation?
Yes, in A2 Incompatible KTX with anti IgG AB monitoring daily in the first two weeks as there is risk of antibodies rebound after transplantation so preferred monitoring in the first two weeks then three time /week for another two weeks then weekly till 3 months, no standard protocol for the frequency of monitoring but should be very closely monitored in the first 4 weeks.
If no, what are your other options?
Kidney paired donation or DD program
References:
1-Azzi Y, Nair G, Loarte-Campos P, Ajaimy M, Graham J, Liriano-Ward L, Pynadath C, Uehlinger J, Parides M, Campbell A, Colovai A, Alani O, Le M, Greenstein S, Kinkhabwala M, Rocca J, Akalin E. A Safe Anti-A2 Titer for a Successful A2 Incompatible Kidney Transplantation: A Single-center Experience and Review of the Literature. Transplant Direct. 2021 Jan 26;7(2):e662. doi: 10.1097/TXD.0000000000001099. PMID: 33521251; PMCID: PMC7837880:
2-Masaki Muramatsu et al,ABO incompatable renal transplant, Good or bad?.World journal of transphttps://fship.worldkidneyacademy.org/user-account/#settingslantation.2014
Excellent
▪︎Will you go ahead?
I will go ahead as this is living related donor with good HLA matching 110 mismatch, no DSAs
Regarding blood group
A2-incompatible transplantation is safe in patients with anti-A2 titers ≤16 with excellent short-term kidney allograft outcomes.
C4d positivity is frequent in allograft biopsies without acute rejection.
▪︎Any other invistigations required?
CDC XM ,FCXM
to detect non DSA antibodies.
▪︎If yes, what is your immunosuppression plan?
This recipient has no DSAs, 110 mismatch no mismatch at DR ,if negative CDC ,no desensitization is needed and he is considered intermediate risk as the incompatibility in blood group Is low titre and mostly Donor kidneys from individuals of the A2 blood group subtype are inherently less immunogenic
Induction with basiliximab and triple immunosuppression with tacrolimus, steroids and MMF.
▪︎If yes, do we need to monitor the anti-A antibody titre post-transplantation?
Daily measurement of HLA or ABO antibody levels is not mandatory, but daily samples should be taken when in hospital and at each clinical visit
Monitoring of the titer may be done on alternate days in the first two weeks
Or if impaired graft function
Protocol biopsy also may be done for early detection of AMR
transplantation appears to be safe in patients with anti-A2 titers ≤16 without desensitization with excellent patient survival (100%) and graft survival (90%) at a median follow-up close to 3 y.
▪︎If no, what are your other options?
Paired Donation program
Yorg Azzi, MD, Gayatri Nair,et Al.Safe Anti-A2 Titer for a Successful A2 Incompatible Kidney Transplantation: A Single-center Experience and Review of the Literature.Transplant Direct. 2021 Feb; 7(2): e662.
Excellent
1- will go go ahead
young male, blood group A2 and titre is 1/2 with no DSA. it should be low risk of rejection for this patient
2- FXCM in case there is non-HLA antibodies, post transplant anti-A titre to predict rebound
3-If yes, what is your immunosuppression plan?
No Desensitization required. Low immunological risk so my induction choice will be Basiliximab given D0 and D4, Methylprednisolone 500mg at operation theater and maintain with triple therapy: MMF, Tac and prednisolone
4-If yes, do we need to monitor the anti-A antibody titre post-transplantation?
Yes, i would monitor daily for a week, if stable and no rebound, every other day for a week or two then stop monitor it
5-If no, what are your other options?
Paired kidney exchange
Deceased donor transplant – with better matched
Excellent
Will you go ahead?
Yes , I will.
This living related with good HLA matching and in compatible ABO group for A2 with low titer which is less immunogenic with safe out-come (1).
Any other investigations required?
Cross match.
cPRA.
If yes, what is your immunosuppression plan?
No need for desensitization as titer less than ½ and good matching
Induction with basiliximab ((20 mg on days 0 and 4 of transplantation) and tacrolimus triple based therapy.
If yes, do we need to monitor the anti-A antibody titre post-transplantation?
Yes, monitored daily or on alternate days for 1 week, twice a week in the 2nd week, and weekly for next 4 weeks. Additional checking was done if clinically indicated(2).
If no, what are your other options?
If not accepting this .
Better to involve him in PKD.
Deceased donor waiting system .
References:
1- Azzi Y, Nair G, Loarte-Campos P, Ajaimy M, et al,. A Safe Anti-A2 Titer for a Successful A2 Incompatible Kidney Transplantation: A Single-center Experience and Review of the Literature. Transplant Direct. 2021 Jan 26;7(2)
2- Shah BV, Rajput P, Virani ZA, Warghade S. Baseline Anti-blood Group Antibody Titers and their Response to Desensitization and Kidney Transplantation. Indian J Nephrol. 2017;27(3):195-198. doi:10.4103/0971-4065.202402.
Excellent
Yes I will go ahead with transplant
Pre transplant CDC cross match is needed
Basiliximab with triple immunosupression
We really do not need to monitor anti A antibody titers
Paired exchange program can be another option
Excellent
I agree in principle with your monitoring plan
• Will you go ahead?
The donor has blood group of A2 or non-A1 which has low immunogenicity and usually is not highly expressed in the endothelial and epithelial donor kidney.
According to KDIGO stratification 2009 of high risk transplantation, the recipient is young (and we don’t don’t know if the donor is old), mismatch 110( more than 0), and ABO incompatible (although the donor is A2 blood group), and no information about crossmatch (although no DSA, but recipient could have non-DSA or non-HLA), So it is considered high risk for rejection.
But ignoring the ABO incompatibility, and having only 2 mismatches at classic HLA loci, and no sensitization history, the risk is considered low and I will proceed with transplantation.
• Any other investigations required?
Crossmatch should be done pretransplant as routine workup at least CDC, if positive transplantation shoukd be avoided, if negative flowcytometry crossmatch should follow.
• If yes, what is your immunosuppression plan?
As presented in the lecture many protocols have been tried, using different induction and maintenance immunosuppression. In this case, based on the KDIGO high risk stratification, I would proceed with r-ATG induction followed by triple maintenance therapy CNI based. Some protocols included r-ATG as induction rather thn basiliximab.No rituximab is needed or plasmapheresis in the pre-transplantation period as the iso-agglutunin titers are very low and do not appear to cause AMR.
• If yes, do we need to monitor the anti-A antibody titer post-transplantation?
Having very low pretransplant titers, and low expression and immunogenicity of A2, the monitoring is unnecessary unless there is alteration in kidney function or DGF, but protocol biopsy should apply here even in the context of normal kidney function to look for subclinical AMR.
• If no, what are your other option?
Paired exchange program is the appropriate program to match ABO compatible donor.
excellent reasoning.
Great to ask for cross match as although no DSAs but non HLA could be looked for.
Follow up question in this particular patient with low anti IGg titre do you need to follow up that post TX. And if yes how frequent.
In this particular patient with low pretransplant titers of isoagglutinins, it is wise to measure the titers in the first 2 weeks, as after 2 weeks there is the accomodation phenomenon, in which the rise in antibody titers is expected after 2 weeks but this rise is not associated with deleterious effects.
Thank you, Mohamed,
Well presented, but I disagree with ATG induction since it is a very low risk regarding the ABO antigen and also HLA antigens. Just basiliximab induction would be enough.