3. A 34-year-old CKD 5 patient received an offer from his sister (36-year-old), 112 mismatch, blood group incompatible (donor is blood group AB, the recipient is blood group A, with anti-B antibody titre of 1/4). The recipient has DSAs (anti HLA- A23 with MFI 7350, anti-DR7 with MFI 5646, anti-DQ2 with MFI 8781 and anti-DR53 with MFI 20128).
- Would accept this donor?
- If yes, what is your immunosuppression plan?
- If no,would you accept another donor who is HLA compatible but ABO incompatible?
- If no, would you accept another donor who is ABO compatible but HLA incompatible?
- What are the potions avialable?
Thank you for your contribution, few questions based on your answers
1. Will you use ATG induction and Rituximab induction in this case? Justify your answer, please!
2. Regarding postoperative monitoring, Will you monitor both ABO titre and the DSA?
3. If you have a choice to monitor either DSA or ABO titre, which one you will choose?
4. What do you expect the crossmatch would be? Please justify the answer!
1. I will use ATG because the patient has 2 DR mismatches plus high DSA MFI against DR & DQ. But not necessarily rituximab due to low A/B antibody titer.
2. I will monitor DSA, but not necessarily ABO titer, except if he develops graft dysfunction.
3. DSA
4. POSITIVE, due high DSA MFI
1. I would use ATG induction for HLA mismatch especially in DR which carries worse prognosis.
I think addition of rituximab will cause marked immune suppression, we can give it as rescue treatment in case of AMR.
2. I think it wise to monitor both DSA and anti B iso agglutinin titers for early detection of Acute rejection and timely intervention in such high risk patient.
3. For sure, when I have to choose one antibody testing, it will be DSA because he has already Mismatch on HLA DR level, and have preformed DSA with high titers unlike anti B which is acceptable titer.
4. Cross match will be postive at the level of FXM and I think on level of CDC because high MFI DSA is detected.
1- ATG induction as we have less HLA match, with high DSA against some antigens
2- i will monitor DSA 1st and ABO titer can be monitored
3- i will choose DSA to be monitored dt low titer of anti-B antibody
4- cross match expected to be negative, because of low titer of anti-B antibody
we do not have HLA typing of the recipient and donor to compare antigens in the donor with DSA of the recipient
so i cannot judge about cross match except after knowing tissue typing of both donor and recipient
1. Will you use ATG induction and Rituximab induction in this case? Justify your answer, please!
Yes ATG and Rituximab induction in such a case can be used as it is considered a highly sensitised case with HLA mismatch with high level of DSA ,increased MFI for DR, DQ.
Fang JL et al study concluded that immune-induction therapy that combines Rituximab with ATG can significantly inhibit lymphocyte proliferation. It is effective and safe in treating hypersensitive patients. The survival rate of hypersensitive patients in the short and medium term is comparable to those with low immune risk. (1)
2. Regarding postoperative monitoring, Will you monitor both ABO titre and the DSA?
I would monitor DSA mainly and ABO can be monitored if there is noticed graft dysfunction
3. If you have a choice to monitor either DSA or ABO titre, which one you will choose?
DSA titer in this case
4. What do you expect the crossmatch would be? Please justify the answer!
CDC and FCXM are expected to be positive.
A cut-off MFI value of 3000 for Luminex SAB-based assay was found to significantly correlate with the FCXM positivity while a MFI value of 7000 and above predicted a positive CDC crossmatch. MFI cut-off value obtained as a surrogate marker for CDC and FCXM tests will help in resolving the limitations of different cell-based techniques.(2)
Reference
1-Fang JL, Chen Z, Guo YH, Ma JJ, Pan GH, Li GH, Xu L, Zhang L, Lai XX, Yin W, Yao ZP, Chen LB. [Clinical efficacy and safety of combined induction therapy with rituximab and ATG in highly sensitized kidney transplant recipients]. Zhonghua Yi Xue Za Zhi. 2019 Apr 23;99(16):1232-1236.
2- Baranwal AK, Bhat DK, Goswami S, Agarwal SK, Kaur G, Kaur J, Mehra N. Comparative analysis of Luminex-based donor-specific antibody mean fluorescence intensity values with complement-dependent cytotoxicity & flow crossmatch results in live donor renal transplantation. Indian J Med Res. 2017 Feb;145(2):222-228.
I will use Rituximab for desensitization protocol (if we decide to consider desensitization)in combination with ATG induction as he is high risk transplant.
Indication for desensitization
1) cPRA more than 30% considered sensitized and qualify for desensitization.
2) Positive CDC ,no desensitization recommended,seek PKD or KAS.
3) Negative CDC and positive FCX, then depend on strength and quality of DSAs
If FCX with MCS of more than 250 it’s contraindicated for desensitization.
FCX MCS less than 250 then depend on RIS if more than 17 .contraindicated for desensitization.
In patient, RIS is more than 17( 10 score for every 10000 MFI,5 for 5000-9999,and 2 for less than 5000). It’s very unusual to have FCX of less than 250 when RIS is more than 17, nevertheless I would consider CDC and FCX to verify.
For post operative monitoring ,I will monitor both of them DSAs and Anti B antibodies.
If only one option ,I will go for DSAs monitoring, as Anti B titer is very low risk and accomodation will be there after 2 weeks.
I think cross match will be positive giving the high RIS as I explained earlier.
Reference:
Edmond Huang and Stanly C Jordan.Kidney transplantation in adult: HLA desensitization. March 2022.www.uptodate.com
I will not transplant this case due to very high MFI DSA with RIS> 17, especially if MCS > 250, and if associated with a positive crossmatch , but if the patient is transplanted , desensitization using Rituximab, plasmapheresis and IVIG should be done and induction should be aggressive with ATG
if all is done there is very high risk of hyperacute rejection and graft loss
AntiABO titer and DSA level should be monitored postoperatively for the risk of rebound increase after desensitization, monitoring of DSA in this case is more importetnt than monitoring of antiABO titer
DSA should be monitored once in early post-transplant period (first 3 month) , then every 3 months till 2 years post-transplantation the annually
Monitoring of isoagglutinin titers daily till discharge from the hospital, then 2-3 times per week for the first month then weekly till 3 m post-transplant then annually
Most probably cross match will be positive since there is a cutoff MFI level which usually result in a positive crossmatch which is 2000 in HLA class I, and 5000 in HLA class II
1. Yes will use ATG and rituximab
2. Serial monitoring to DSA level and anti A/B antibodies titer daily first week and then weekly
3. DSA level because it’s very high and high risk of rejection
4. it’s positive cross match
reference
1-Christian Morath,1 Gerhard Opelz,2 Martin Zeier,1 and Caner Süsal2.Clinical Relevance of HLA Antibody Monitoring after Kidney Transplantation.Journal of Immunology Research Volume 2014, Article ID 845040,
5pages.http://dx.doi.org/10.1155/2014/845040.
1. Will you use ATG induction and Rituximab induction in this case? Justify your answer, please!
2. Regarding postoperative monitoring, Will you monitor both ABO titre and the DSA?
3. If you have a choice to monitor either DSA or ABO titre, which one you will choose?
4. What do you expect the crossmatch would be? Please justify the answer!
1- as the DSA levels are high, I will do desensitization with rituximab+plasmapharesis+IVIG.
2- I will monitor both, as it is high-risk transplant, even with low titer isoagglutinin
3- DSA monitoring will have priority
4- positive crossmatch is expected with this high DSA level
1. Will you use ATG induction and Rituximab induction in this case? Justify your answer, please!
This is a case involving a highly sensitized patient with ABO incompatible donor, representing a dual risk. Using a dual induction involving ATG and rituximab is a more prudent approach. It has been shown that using a combination of ATG and rituximab in highly sensitized patients is associated with better graft survival.(1)
2. Regarding postoperative monitoring, Will you monitor both ABO titre and the DSA?
Post-operatively, it is important to monitor DSA levels once in first three months, then annually or whenever there is any graft dysfunction, alteration in immunosuppression or suspicion of non-adherence.(2,3)
Graft dysfunction due to ABO incompatibility can happen in first 3-4 weeks, hence antibody titre monitoring is needed.
The ABO titre also needs to be monitored as graft dysfunction can occur due to ABO incompatibility alone, which usually responds to antibody removal alone, while AMR will require more aggressive treatment.
3. If you have a choice to monitor either DSA or ABO titre, which one you will choose?
If I have to choose one, I would rather follow the DSA level in this case due to presence of high MFI DSAs while the ABO titre is low and their significance lies only for first 3-4 weeks.
4. What do you expect the crossmatch would be? Please justify the answer!
Due to high levels of MFI, the crossmatch is expected to be positive. MFI more than 3000 correlates with FCXM positivity, while more than 7000 correlates with CDC crossmatch positivity.(4)
Reference:
1) Laftavi MR, Pankewycz O, Feng L, Said M, Patel S. Combined induction therapy with rabbit antithymocyte globulin and rituximab in highly sensitized renal recipients. Immunol Invest. 2015;44(4):373-84. doi: 10.3109/08820139.2015.1014097. PMID: 25942348.
2) Tait BD, Süsal C, Gebel HM, Nickerson PW, Zachary AA, Claas FH, et al. Consensus guidelines on the testing and clinical management issues associated with HLA and non-HLA antibodies in transplantation. Transplantation. 2013 Jan 15;95(1):19-47. doi: 10.1097/TP.0b013e31827a19cc. PMID: 23238534.
3) Crespo M, Zárraga S, Alonso Á, Beneyto I, Díaz Corte C, Fernandez Rodriguez AM, et al; GREAT Study Group and Spanish Network for Research in Renal Diseases (REDINREN, RED16/0009). Monitoring of Donor-specific Anti-HLA Antibodies and Management of Immunosuppression in Kidney Transplant Recipients: An Evidence-based Expert Paper. Transplantation. 2020 Aug;104(8 Suppl 2):S1-S12. doi: 10.1097/TP.0000000000003270. PMID: 32658025.
4) Baranwal AK, Bhat DK, Goswami S, Agarwal SK, Kaur G, Kaur J, Mehra N. Comparative analysis of Luminex-based donor-specific antibody mean fluorescence intensity values with complement-dependent cytotoxicity & flow crossmatch results in live donor renal transplantation. Indian J Med Res. 2017 Feb;145(2):222-228. doi: 10.4103/ijmr.IJMR_222_16. PMID: 28639599; PMCID: PMC5501055.
1- Yes I will use Rituximab for desensitization and ATG for induction as there is high immunological risk.
2- Yes I will monitor the 2 . Both are important with regard to AMR.
3-DSA as Accommodation can develop after 2 weeks in ABOi
4-positive crossmatching due to high MFI DSA
1. Will you use ATG induction and Rituximab induction in this case? Justify your answer, please!
ATG because he had 2 DR mismatch
DSA with high MFI
2. Regarding postoperative monitoring, Will you monitor both ABO titre and the DSA?
Yes I will monitor both because the risk of AMR is higher in this patient ,he had double hits
3. If you have a choice to monitor either DSA or ABO titre, which one you will choose?
ABO because the risk of AMR is higher with ABOi
4. What do you expect the crossmatch would be? Please justify the answer!
Will be positive because he had very high level of DSA towards DR 53(MFI 20128)
Will you use ATG induction and Rituximab induction in this case? Justify your answer, please!
Yes, this is a high-risk transplant ( HLAi & ABOi, despite the low titer of Anti-B ab but there is a DSA with significant MFI), need aggressive induction with ATG and rituximab.
Regarding postoperative monitoring, Will you monitor both ABO titre and the DSA?
For ABO antibody, it needs monitoring in the first 2 weeks post-transplant to detect rebound and the risk for ABMR.
For DSA, yes I should monitor it closely and if possible protocol biopsy needs to be done to detect subclinical rejection.
If you have a choice to monitor either DSA or ABO titre, which one you will choose?
I will monitor DSA, it is of class I & II with high titer.
What do you expect the crossmatch would be? Please justify the answer!
Positive crossmatch due to high MFI DSA.
1- ATG for induction as he has significantly high DSA especially to DR AND DQ which is associated with poor graft outcome,
rituximab was mentioned to improve outcomes in ABOI-KT BUT in this case the titre is low so we go without rituximab to avoid the risk of aggressive immunosuppression and infection .
2 i wil follow up ABO titre in the fisrt 2 weeks till accommodation Occurs and I will follow up DSA as well.
3-DSA AS the pretransplant DSA is very high,ABO if graft function started to be impaired.
4 high DSA level means significant titreof antibodies that causes positive crossmatch
1. Will you use ATG induction and Rituximab induction in this case? Justify your answer, please!
ATG due to the high risk of ABM rejection
in addition to Rituximab for B cell depletion post-plasmapheresis (as apart for desensitization protocol )
2. Regarding postoperative monitoring, Will you monitor both the ABO titer and the DSA?
Both to be monitored A/B antibodies 2week post-transplant for early detection of high titer with the prediction of AB MR
DSA is mandatory due to the presence of preformed DSA
3. If you have a choice to monitor either DSA or ABO titre, which one you will choose?
DSA ( due to pre-transplant high level with high RIS )
A/B titer pre-transplant was low 1:4 can be done only if associated with allograft dysfunction
4. What do you expect the crossmatch would be? Please justify the answer
CDC and flowcytometry crossmatch will be positive
due to the presence of DSA with a high level against both class I, II with high RIS
Better use ATG Induction with DSA monitoring
Crossmatch will be positive due to high MFI DSA titre
Would accept this donor?
Nope. High immunological risk with poor graft outcome.
If yes, what is your immunosuppression plan?
Desensitization :Cycle of plasmapheresis with IV IG +/- IV Rituximab.
Induction : ATG.
Maintenance with Tacrolimus MMF Steroid.
Serial DSA and renal profile.
If no,would you accept another donor who is HLA compatible but ABO incompatible?
No
If no, would you accept another donor who is ABO compatible but HLA incompatible?
No
What are the potions avialable?
Paired kidney exchange program. Deceased kidney donor.
Would accept this donor?
I wouldn’t accept this donor for the followings: 2DR mismatch within the 1-1-2 HLA mismatch, ABOi although low ABO titre, high DSA level for HLA-A and DR and high anti-DQ which is associated with high risk of ABMR .
If yes, what is your immunosuppression plan?
If I accept this donor, I will follow the followings:
1. Desensitization therapy; DFPP, IVIG and RTX.
2. Induction with ATG or RTX.
3. For maintenance IS: TAC, MMF and Prednisolone.
If no,would you accept another donor who is HLA compatible but ABO incompatible?
Yes, I would accept ABOi donor with precautions and pre-TX treatment for ABOi-rTX.
If no, would you accept another donor who is ABO compatible but HLA incompatible?
Yes, I will accept HLAi donor with desensitization protocol beside induction therapy with ATG and intense IS regimen.
What are the potions avialable?
1. PKD
2. Altruism
3. Waiting list for deceased donation.
4. Or to go on long lasting dialysis.
* Would accept this donor?
I would not accept this donor, because there are HLA incompatibility (1-1-2), ABO incompatibility ( A and AB) with anti -B antibody titre of 1/4, with a Positive DSA against (HLA -A, DR, DQ ) with high level MFI , So we can expect positive crossmatch in such case.
(A cut-off MFI value of 3000 for Luminex SAB-based assay was found to significantly correlate with the FCXM positivity while a MFI value of 7000 and above predicted a positive CDC crossmatch. MFI cut-off value obtained as a surrogate marker for CDC and FCXM tests will help in resolving the limitations of different cell-based techniques).(1)
* If yes, what is your immunosuppression plan?
This highly sensitized patient need desensitization protocol with plasmapheresis , IVIG, Induction with r-ATG and maintenance triple I.S ( Tac, MMF, Steroid), and postoperative monitoring of the DSA level , and the ABO antibody titre should be done when there is graft dysfunction.
* If no,would you accept another donor who is HLA compatible but ABO incompatible?
Yes, I would accept donor with HLA compatible but, ABO incompatible with low level of ABO antibody titre, due to good graft outcome
* If no, would you accept another donor who is ABO compatible but HLA incompatible?
No, Iwould not accept donor with ABO compatible but HLA incompatible because, HLAi was a more important risk factor for BPAR compared with ABOi.(2)
* What are the potions avialable?
Paired kidney exchange donation program
* References
(1) Ajay Kumar Baranwal, Deepali Krishan Bhat, Sanjeev Goswami, Sanjay Kumar Agarwal, Gurvinder Kaur, Jasmeet Kaur, Narinder Mehra. The Indian journal of medical research 145 (1), 222, 2017.ite
(2) Ko EJ, Yu JH, Yang CW, Chung BH; Korean Organ Transplantation Registry Study Group. Clinical outcomes of ABO- and HLA-incompatible kidney transplantation: a nationwide cohort study. Transpl Int. 2017 Dec;30(12):1215-1225. doi: 10.1111/tri.12979. Epub 2017 Jul 6. PMID: 28493630.
I would decline this donor, high risk transplantation with very high donor specific antibodies.
I would suggest plasma exchange sessions frist,
using ATG for induction ; and as maintenance i would use MMF, Tacrolimus and steroids,
Yes, I would. as ABOi transplantation with HLA compatibility can be performed.
No.
Search for better matched donor.
paired kidney donation.
Would accept this donor?
I would not accept this offer.
This is a high immunological renal transplant offer, ABO incompatible, MM 112, preformed DSAs with high titers, cross match is expected to be positive.
If yes, what is your immunosuppression plan?
Needs desensitization: Plasma exchange, IVIG, Rituximab.
Induction: ATG
Maintenance: Tacrolimus+steroids+MMF.
Monitor: DSA s, anti isoagglutinin, Tacrolimus level, renal function tests.
If no, would you accept another donor who is HLA compatible but ABO incompatible?
yes,
ABOi transplant with anti-A/B antibody titer below 1/512 can be desensitized till titer below 1/8, so transplantation can be done with similar graft survival compared to HLA compatible transplants.
If no, would you accept another donor who is ABO compatible but HLA incompatible?
Yes,
He will need desensitization before transplantation if DSAs MFI above 3000, and positive cross match
What are the potions available?
Paired kidney exchange scheme, wait for another well matched donor.
Thank you for your contribution, few questions based on your answers
1. Will you use ATG induction and Rituximab induction in this case? Justify your answer, please!
Yes, I will use ATG + rituximab because it is high risk transplant offer, with heavy immunosuppression, better graft survival and less acute rejection is expected. However, it is very high risk of immunosuppressive complications especially infections and malignancy.
2. Regarding postoperative monitoring, Will you monitor both ABO titre and the DSA?
Yes, I will monitor both
3. If you have a choice to monitor either DSA or ABO titre, which one you will choose?
DSA
4. What do you expect the crossmatch would be? Please justify the answer!
Expected to be positive with this very high DSA titers.
◇Would accept this donor?
_____________________________
NO, I will not accept this donor due to different reasons:
1. Combined HLA and ABO incompatability
( 2 DR mismatches and the donor is bloodgroup AB and the recipient is bloodgroup A).
2) This is a highly sensitized recipient with DSA against both class I and class II and high DSA (anti HLA- A23 with MFI 7350, anti-DR7 with MFI 5646, anti-DQ2 with MFI 8781 and anti-DR53 with MFI 20128).
◇ If yes, what is your immunosuppression plan?
__________
▪︎Desensitization with Plasmapheresis and IVIG until crossmatch and anti-B titre become negative.
▪︎Rituximab
▪︎Induction with ATG
▪︎Maintenance therapy: based on triple immunosuppression therapy including: Tacrolimus, MMF and prednisolone.
▪︎This pt requires close post transplant follow up with repeated measures of DSAs and anti blood group B titre.
▪︎Monitor the trough level of tacrolimus.
◇If no, would you accept another donor who is HLA compatible but ABO incompatible?
___________________
▪︎I would accept a donor who is HLA compatible but ABO incompatible, but the antibody titres are important.
▪︎Anti-B antibodies are aimed to be below a certain threshold at the time of ABOi kidney transplantation and during the first 2 weeks after surgery (1).
◇If no, would you accept another donor who is ABO compatible but HLA incompatible?
__________________
▪︎I would accept a donor who is ABO compatible but HLA incompatible, but this rely upon the interplay of numerous factors: better identification of incompatible antigens, the level of DSA and desensitization procedures before transplantation, improved pharmacotherapy for inhibition of antibody synthesis and evolving immunosuppressant protocols to provide adequate prophylaxis against cell and/or antibody-mediated rejection.
◇ What are the options available?
____________________________________
1) Search for a new donor
who is ABO and HLA compatible
2) Enroll in kidney paired exchange program
c) Wait for a deceased donor kidney.
__________
Ref:
Christian Morath, Martin Zeier, et al. “ABO-Incompatible Kidney Transplantation.
https://dx.doi.org/10.3389/fimmu.2017.00234
[2] A. Sharing, et al “Incompatible kidney transplantation: a brief overview of the past, present and future”
QJM: An International Journal of Medicine, Volume 105, Issue 12, December 2012, Pages 1141-1150.
https://doi.org/10.1093/qjmed/hcs154
No, It carries a high immunological risk with 2 HLA-DR mismatches, DSA with high MFI against both class I and II with RIS 25 (>17) with probablyly positive FCXM
Desensitization with plasmapheresis, IVIG till have a negative FCXM and rituximab
Induction with ATG as it is high immunological risk
triple maintenance therapy with tacrolimus, MMF and steroids
yes, as graft survival in ABOi transplant are nearly similar to HLA compatible transplants with considering the anti-A/B antibody titer if <1/512 ABOi transplant can be performed after desensitization and lowering the titer to <1/8
yes, after assessment of the immunological risk with considering degree of HLA mismatch, DSA, RIS and FCXM result
paired kidney donation as he has a live donor
remaining on waiting list for deceased donor
Would accept this donor?
This case pertains to combined ABO incompatibility and HLA incompatability.
Although the anti-B antibody titres are 1:4 in this patient (suggesting relatively easy to cross the ABO barrier), there are other issues in this donor-recipient pair.
No. I will not accept this donor.
Reasons:
1) Degree of HLA mismatch: There is 2 DR mismatch in this case, which is associated with poor graft outcomes. Even a single DR mismatch has poor graft outcomes and hence should be avoided. (1,2)
2) Presence of DSA: DSA against both class I and class II, with high MFI, are present in this case. The DSA-RIS score is > 17 (5+5+5+10 = 25), hence it would not be prudent to use desensitization in this patient.
· If yes, what is your immunosuppression plan?
This patient should not be desensitized and transplanted due to high immunological risk.
If we do take up this patient for transplant then the patient will require desensitization with Plasmapheresis and IVIG to achieve a negative crossmatch before proceeding with the transplant.
The anti-B antibody titres will also go down due to the plasmapheresis and IVIG.
Injection Rituximab 200 mg IV 2 weeks prior to the tentative date of transplantation.
Since this patient is a high immunological risk category patient, the patient will require induction immunosuppression and tacrolimus based triple drug maintenance immunosuppression.
1) Induction therapy: Injection Anti Thymocyte Globulin (ATG) in dose of 1-1.5 mg/kg per day for 4-6 days (total dose 6 mg/kg).
2) Maintenance immunosuppression: Triple drug therapy including
a. Tacrolimus: Target trough level of 8-10 ng/ml
b. Mycophenolate mofetil (MMF): 1000 mg twice a day
c. Corticosteroids: Injection methylprednisolone 500 mg intravenous on the day of surgery, followed by tablet prednisolone 1mg/kg/day for 3 days and then 20 mg/day, to be tapered to 5 mg/day over next 6 to 8 weeks.
Steroid-free regimen should not be used in this case.
CMV and pneumocystis prophylaxis should be given.
Post-transplant, patient requires close follow-up with clinical and laboratory evaluation.(4)
i) Complete blood count, urine examination and serum creatinine. Tacrolimus trough levels to be monitored.
ii) Anti-B antibody titres monitoring: daily for first 2 weeks, then twice a week for next 2 weeks.
iii) To look for proteinuria: Spot urine protein-to-creatinine ratio.
iv) DSA testing: Once in first three months, then annually or whenever there is any graft dysfunction, alteration in immunosuppression or suspicion of non-adherence.(5,6)
v) Protocol biopsy: Once in first three months. If the biopsy shows features of AMR, it should be treated.
· If no, would you accept another donor who is HLA compatible but ABO incompatible?
I would accept a donor who is HLA compatible but ABO incompatible, but the antibody titres are important.
Pre-transplant maximum isoagglutinin titres have a bearing on graft outcomes, with higher titres showing poor outcomes. If the titres are >1:512, the chances of successful transplantation are low and due to requirement of increased plasmapheresis, there are increased risks of infections and surgical complications due to increased bleeding tendencies. Patients with titres ≥1:256 have been shown to have increased risk of AMR. (8)
So, if the isoagglutinin titres are <1:512, ABO incompatible transplants can be taken up.
· If no, would you accept another donor who is ABO compatible but HLA incompatible?
I would accept a donor who is ABO compatible but HLA incompatible, but the level of DSA are important.
The DSA-RIS score guides us in taking up patients for desensitization and transplant.
· What are the options available?
The other options available in this scenario include:
a) Change the donor to someone who is compatible (ABO and HLA)
b) Enroll in kidney paired exchange program
c) Wait for offer through the deceased donor program
References:
1) Connolly JK, Dyer PA, Martin S, Parrott NR, Pearson RC, Johnson RW. Importance of minimizing HLA-DR mismatch and cold preservation time in cadaveric renal transplantation. Transplantation. 1996 Mar 15;61(5):709-14. doi: 10.1097/00007890-199603150-00007. PMID: 8607172.
2) Shi X, Lv J, Han W, Zhong X, Xie X, Su B, Ding J. What is the impact of human leukocyte antigen mismatching on graft survival and mortality in renal transplantation? A meta-analysis of 23 cohort studies involving 486,608 recipients. BMC Nephrol. 2018 May 18;19(1):116. doi: 10.1186/s12882-018-0908-3. PMID: 29776389; PMCID: PMC5960106.
· Would accept this donor?
No, as there is a double risk of ABM rejection ( due to Incompatible ABO transplantation ) in addition to the presence of DSA against 2 classes I, II with high MFI with high RIS
· If yes, what is your immunosuppression plan?
Plan good desensitization protocol using ( Plasmapheresis + Rituximab or IVIG )and assessment of PRA single antigen of 2 classes and crossmatch negative (CDC + flowcytometry )
Induction includes ATG
Maintenance on Steroids + MMF + high level prograf
Follow up anti-ABO antibodies titer + DSA after transplantation +- Biopsies protocol
· If no, would you accept another donor who is HLA compatible but ABO-incompatible?
Yes to shorten the waiting time for transplantation with better quality of life for the recipient
with precautions A/B antibodies titer before transplantation to be less than 1:32
with the protocol for reduction of antibodies titer ( Rituximab + IA or plasmapheresis )
· If no, would you accept another donor who is ABO compatible but HLA incompatible?
Yes to shorten the waiting time for transplantation with better quality of life for the recipient
with Desensitization protocol ( Rituximab + Plasmapheresis ± IVIG ) with a target of reduction of DSA MFI to lowest level + negative both CDC and flowcytometry cross matches
· What are the options available?
PKD
waiting for a suitable donor on the waiting list of deceased donor
No I will not accept this donor as this case shows combined ABO incompatibility and HLA incompatibility so double the risk .
There are DSA against both class I and class II.The DSA-RIS score is > 17 .
If yes, what is your immunosuppression plan?
The patient will require desensitization with Plasmapheresis and IVIG + Mabthera to achieve a negative cross-match before proceeding with the transplant.
The anti-B antibody titres will also go down due to the plasmapheresis and IVIG.
Induction immunosuppression with ATG and tacrolimus based triple drug maintenance immunosuppression.
CMV and pneumocystis prophylaxis should be given.
If no, would you accept another donor who is HLA compatible but ABO incompatible?
I would accept a donor who is HLA compatible but ABO incompatible, but will check the antibody titres.
If no, would you accept another donor who is ABO compatible but HLA incompatible?
I would accept a donor who is ABO compatible but HLA incompatible, but will check the DSA-RIS score .
What are the options available?
-kidney paired exchange.
-program or checking for deceased donor .
Q1: I won’t accept this donor because of 4/6 HLA mismatch with high MFI (more than 6000 for A23 and DQ2, DR53). This is a high immunological risk TX and there is high risk for hyper acute rejection.
Q2: Aggressive desensitization regarding HLAi-TX and so, aggressive immunosuppression is needed if you perform TX.
Desensitization with plasmapheresis and IVIG and rituximab for HLAi-TX and then induction with ATG.
Q3: Yes, I would accept. If donor’s Ab titers are acceptable (below 1:256)
Q4: I would accept an ABO compatible but HLA in compatible if level of DSA is low and XM could be negative after desensitization.
Q5: Another options are:
1- Choosing another donor by KPD program who is ABO and HLA compatible.
2- Waiting for an ABO and HLA compatible deceased donor.
Would accept this donor?
I will not accept the offer , pt had cumulative DSA about 41000 MFI ,and he will go for incomatible kidney transplant with risk of ABMR , this very risky transplnation and i will not accept it .
if no,would you accept another donor who is HLA compatible but ABO incompatible?
Yes if the pt has a donor with HLA comatibilty and ABOi with this low titre with anti B antibody as low as that , i will accept.
If no, would you accept another donor who is ABO compatible but HLA incompatible?
No , patient still young , transplantation is very risky , he may need another transplantation in future .
What are the potions avialable?
Even PKD is the best choice for them , but if not availble in his country we have to put him in waiting list and continue on RRT
I would accept this donor, despite being high risk. It would require an induction of immunosuppression for high risk. There is no indication of pre-transplant desensitization due to low titers, however, a protocol of titration and post-transplant biopsy should be performed in the first four weeks.
I would do induction with ATG + maintenance with CNI + MMF + Corticosteroid. Initially, the use of Rituximab is determined in protocols that use desensitization in case of ABOi, although the rationale of avoiding T-cell mediated rejections can be maintained.
This couple has a very high risk of rejection. we have both DSA with high MFI, !!’ mismatch and ABO incompatibility. I would prefer kidney pain donation. except if obligatory for reasons like no other donor acceptable, one can proceed after desensitization protocol including plasmapheresis IVIG rituximab followed by triple immunosuppression (TAC/MMF/MP) with close monitoring of DSA ant anti B titers
Would accept this donor?
No I wouldn’t. It is high immunological risk ( HLA mismatch 2DR , high DSA levels , ABOi even if low isoaglutinine titter ) and of course positive crossmatching.
If yes, what is your immunosuppression plan?
Aggressive desensitization by plasmapheresis , IVIG and Retuximab
Induction by ATG or Alemtuzumab
Triple maintenance IS by (Tac. , MMF , steroid)
If no, would you accept another donor who is HLA compatible but ABO-incompatible?
Yes I will working in making the titter of ABO antibodies <1/8 by DFPP and Retuximab then proceed with transplantation .
If no, would you accept another donor who is ABO compatible but HLA incompatible?
No I will not accept
What are the options available?
Wait for more suitable donor
Or enroll in PKD program
1-Would accept this donor?
There is high risk ;2 DR mismatch, high DSA
level, ABOi even of low isoagglutinin titer.
2- If yes, what is your immunosuppression plan?
Discussion of risk for both recipient and donor, then we can proceed for desensitization with Rituximub ,plasmaphresis and IVIG
Induction could be with ATG and methylprednisolone and maintenance with Tac, MMF and steroid
3-If no, would you accept another donor who is HLA compatible but ABO-incompatible?
yes, with making the isoagglutinin titer < 1:4 – < 1:32 by double filter plasmapheresis and rituximab
4- If no, would you accept another donor who is ABO compatible but HLA incompatible?
No, especially DR incompatible also high DSA as it is associated with risk of Acute ABMR
5- What are the options available?
paired kidney donation or another more suitable offer.
1-Would accept this donor?
No , I will not accept this donor , it is high risk due to :
HLA mismatch
DSA high
ABOi even of low isoagglutinin titer
2- If yes, what is your immunosuppression plan?
Better to explain to the pt that he is high risk of rejection
Desensitization with Rituximub+plasmapharesis+IVIG
Induction with ATG and methylprednisolone
maintenance with prograf+MMF+steroid
3-If no, would you accept another donor who is HLA compatible but ABO-incompatible?
yes , by measuring Antibodies titer and if more than 1/32 , desensitization by ID , DFPP, Rituximab, IV IG
4- If no, would you accept another donor who is ABO compatible but HLA incompatible?
No, especially DR incompatible also high DSA because of the risk of Acute ABMR
5- What are the options available?
paired kidney donation.
1.I will not accept this donor as DSA with very high MFI with RIS greater than 17 will lead to ABMR…and with DR mismatch at HLA level will lead to very poor graft survival. . 2.I will not take this donor.and i will not attempt the desensitazition …As even after desensitization Chance of ABMR will be very high and Graft survival will be poor… .. 3.yes, i will accept another donor with HLA compatible and ABO incompatible .But i would like to see titre of Antibody of A/B before saying yes to donor..As very high Titre greater than 512 ..difficult to desensitization. . 4.Yes,donor can be accepted but I will see DSA if present ,its MFI and Crossmatch result..before saying yes to the donor. 5.Paired kidney donation and deceased kidney transplant are the options. . 5.
1-Would accept this donor?
ABO is incompatible .The recipient is blood group A ,while the donor is blood group AB with anti-B titre of 1/4 . The HLA mismatches are 4/6 with 2 DR mismatches with DSA(anti HLA- A23 with MFI 7350, anti-DR7 with MFI 5646, anti-DQ2 with MFI 8781 and anti-DR53 with MFI 20128). No given result of cross match . This recipient has a high immunological risk for hyper acute rejection . It is better not to accept his donor and to look for other options .
2-If yes, what is your immunosuppression plan?
1-Desensitization with Plasmapheresis and IVIG in addition to rituximab
2- Induction with ATG
3- Maintenance triple TAC (tacrolimus base with MMF, prednisolone)
4-CMV prophylaxis, PJP prophylaxis .
In addition to antibodies monitoring both DSA and anti B .Protocol kidney biopsy . close monitor for CMV and BKV nephropathy, urinary protein.
3-If no,would you accept another donor who is HLA compatible but ABO incompatible?
I would accept the offer . ABO‐incompatible transplantation in contrast to HLA‐incompatible transplantation, in which persistent isoagglutinin in low titer post-transplant not necessarily associated with graft injury or rejection .The immunosuppressant protocol depend on the blood group of the donor ( A2 less immunogenicity ) and the antibodies titre.
4-If no, would you accept another donor who is ABO compatible but HLA incompatible?
Yes, I would accept such offer .The immunosuppressant regimen depends on the cross match result (if positive desensitization ,induction ATG and maintenance triple TAC . If negative ,induction and maintenance triple TAC ) . Post transplant monitoring of DSA in addition to protocol biopsy .
5-What are the potions avialable?
1-Paired donor exchange
2- Combined desensitization and PKT.
References:
1- Uchida, Junji et al. “Latest insights on ABO-incompatible living-donor renal transplantation.” International journal of urology: official journal of the Japanese Urological Association vol. 27,1 (2020): 30-38. doi:10.1111/iju.14109.
1-Would accept this donor?
I will not accept this donor, its highly risky (2 DR mismatch, > 2 mismatches, DSA high
level, ABOi even of low isoagglutinin titer)
2- If yes, what is your immunosuppression plan?
after explaining the risk to the recipient and donor I will do desensitization with
Rituximub+plasmapharesis+IVIG
the induction will be with ATG and methylprednisolone
maintenance with prograf+MMF+steroid
3-If no, would you accept another donor who is HLA compatible but ABO-incompatible?
yes, after bringing the isoagglutinin titer < 1:4 – < 1:32 by double filter plasmapheresis and rituximab
4- If no, would you accept another donor who is ABO compatible but HLA incompatible?
No, especially DR incompatible also high DSA because of the risk of Acute ABMR
5- What are the options available?
paired kidney donation.
I will not accept this donor .
There is 2 DR mismatch and presence of DSA , high MFI.
the anti B antibody titer is accepted for ABOi-KT.
i will look for another donor who is HLA compatible and can be ABOi.
A good option to go through paired kidney donation programme.
she is considered a high risky donor, it is not accepted to proceed based on the incompatible blood group AB being high antigenic expressing both A and B blood group antigens of the highest risk of acute AMR, plus having DSA of elevated MFI requiring heavy desensitization with more frequent risk of severe infection related to high immunosuppression related complications.
immunosuppression plan would better be stated by plasmapheresis or immunoadsorption if available with the concomitant use of IVIG prior to TX by 2 weeks at least . Rituximab can also be used one month before Rx.
on day zero ATG would be a mindful option as for induction ,besides the triple regimen of immunosuppression tacrolimus, MMF and corticosteroids with regular monitoring for DSA and anti A and B antibody titers with keeping in mind the option of plasmapheresis when needed and protocol biopsy .
yes, it would less antigenic but still risky after crossing the ABO blood group barrier is being achieved in many centers worldwide
yes, after heavy desensitization plan preceding Tx (plasmapheresis, IVIG and rituximab).
paired kidney donation program and deceased donor would be benefit for trial for finding more suitable donor.
Would accept this donor?
1- he is ABO incompatible with his donor.
2- he has DSA with high titre.
1- the donor is a live one.
2- the mismatch is high, 112
If yes, what is your immunosuppression plan?
If no,would you accept another donor who is HLA compatible but ABO incompatible?
If no, would you accept another donor who is ABO compatible but HLA incompatible?
1- if DSA titre is very high, desensitization protocols can be applied.
2- if DSA titre is low, intensive induction therapy can be applied.
What are the potions avialable?
This recipient is ABO incompatible and HLA incompatible
it’s difficult to proceed kidney transplant because high risk of AMR
If yes immunosuppressive use desensitisation protocol by removal antibodies by double filtration plasma exchange plus selective immunoadsorption plus intravenous immunoglobulin plus rituximab and ecliuzmab.
Yes will accept HLA compatible with ABOI
No will not accept HLA incompatible because high risk of graft loss
Another option PKD or another compatible donor
-In this case there is ABO icompatibility with Anti B titer <1/4
HLA mismatch 112
DSAs (anti HLA- A23 with MFI 7350, anti-DR7 with MFI 5646, anti-DQ2 with MFI 8781 and anti-DR53 with MFI 20128).
This match better to be avoided due to HLA mismatch specially DR and high DSA titers indicating high risk of Rejection and poor graft survival .
Ko EJ et al study demonstrated that the incidence of Biopsy Proven Acute Rejection(BPAR) was higher in the HLAi and ABOi + HLAi groups compared to control groups with compatible ABO and HLA ; in contrast, it was not higher in the ABOi group. Pretransplant desensitization therapy for either ABOi or HLAi significantly increased the risk of infection-related mortality. (1)
– It is considered high risk due to HLA mismatch and DSA
But anti B Ab titer is less than ,1/8
Desensitisation with plasma pharesis and IVIG and rituximab
Induction therapy with r ATG
Maintenance triple therapy with Tac , MMF , steroids
With postoperative monitoring of DSA
Prophylaxis against CMV and PJP
Protocol biopsy will be needed post transplantation
– Yes, ABO incompatible and HLA compatible donors has better outcome and less complications if compared with ABO compatible and HLA incompatible donors
With reduction of anti B Ab titer to less than 1<8
– No I would not accept a donor who is ABO compatible and HLA incompatible donors due to the high ABMR risk.
HLAi was a more important risk factor for BPAR compared with ABOi.(1)
– Other options :
Kidney exchange program
Waiting for a more compatible deceased or living donor
Reference
1-Ko EJ, Yu JH, Yang CW, Chung BH; Korean Organ Transplantation Registry Study Group. Clinical outcomes of ABO- and HLA-incompatible kidney transplantation: a nationwide cohort study. Transpl Int. 2017 Dec;30(12):1215-1225
1-NO I will accept this transplantion
●The patient must not be undergoing concurrent human leukocyte antigen (HLA) incompatibility and ABOI
This patient have HLA I,ABOI , 112 mismatch(more than 2 HLA mismatch ),high titer of DSA (anti-DR7, anti-DQ2)
DQ mismatches have been associated with an increased risk of rejection and allograft loss in kidney transplant recipients
that HLA-DR mismatches correlated with poor long-term survival
All these factors make the transplantion having high risk for AMR So I will not precede this transplantion
2-If I will accept to do transplantion we should explain the risk and complications for patient
Desensitization by plasmapharesis ,IVIG,ritiximab
Induction with ATG
Maintenance with TAG,MMF,steroid
Monitoring
*we monitor isoagglutinin titers daily while the patient is in the hospital, two to three times per week for the first month posttransplant, weekly for months 2 to 3 posttransplant, and then yearly thereafter. In patients with a posttransplant isoagglutinin titer ≥1:16, a kidney biopsy and/or preemptive plasmapheresis should be performed, particularly if there is evidence of graft dysfunction (eg, delayed/slow graft function or rising serum creatinine).
*monitor DSA levels at months 1, 3, 6, and 12 posttransplant and then annually
In patients with a significant rise in DSA we perform a renal allograft biopsy.
3-yes ,we can accept patient with HLA compatible and ABO in compatible
But this also depend on DSA titer and cross match
• The risk of TCMR is much higher in HLAi when compared to ABOi transplantation.
4-yes we can accept patient with ABOI and compatible HLA
the total isoagglutinin antibody titer is generally reduced to at least 1:32 (and often to ≤1:8) before proceeding to transplantation as higher titers are associated with acute ABMR posttransplant
5-Other options is to wait for more compatible donor or do paired kidney transplantion
Reference
1-Up to date
2-Nicholas Torpey, Nadeem E Moghal, Evelyn Watson, and David Talbot. OSH Renal Transplantation. Published online: Oct 2011.
Would accept this donor?
No, because :
-both donor and recipient are ABO incompatible.
-recipient has DSA with high MFI and RIS =17 which associated with a positive predictive value of 91% for antibody-mediated rejection)
– There HLA mismatches 112 (2 mismatch at DR carries a high risk for rejection)
If yes, what is your immunosuppression plan?
-Desentiation of the recipient with plasma exchange followed by IVIg.
-Induction with rATG , maintenance immunosuppression with Tac ,MMF, prednisolone.
– Prophylaxis for PJP & CMV infection.
-Follow-up posttransplant for :
-DSA ,Anti-B antibodies
-Tac level,CBC, RFT ,urine analysis
-Protocol biopsies.
If not, would you accept another donor who is HLA compatible but ABO-incompatible?
Yes , ABO-incompatible can be accepted after determining IgG and IgM titer and deciding if the patient needs desensitization or not.
If not, would you accept another donor who is ABO compatible but HLA incompatible?
I will accept donor with ABO compatible but HLA incompatible after doing crossmatch and DSA level and determine if the recipient needs desensitization or not.
-I prefer donor with ABO compatible but HLA incompatible. We have no experience with ABO-incompatible.
What are the options available?
-Search for another living compatible donor
– deceased compatible donor.
– Kidney Paired Donation
Reference:
– Edmund Huang & Stanley C .Rationalizing Incompatible Living Donor Kidney Transplantation for Highly Sensitized Candidates. https://doi.org/10.1007/s40472-021-00329-y
3. A 34-year-old CKD 5 patient received an offer from his sister (36-year-old), 112 mismatch, blood group incompatible (donor is blood group AB, the recipient is blood group A, with anti-B antibody titre of 1/4). The recipient has DSAs (anti HLA- A23 with MFI 7350, anti-DR7 with MFI 5646, anti-DQ2 with MFI 8781 and anti-DR53 with MFI 20128).
Would accept this donor?
No better to find another donor either through PKD program or better DD allocation program with ABO compatible and HLA compatible donor
Rational for rejection this donor:
Double hit ABOI, HLAI from related living donor (his sister with high risk of rejection, due to two Mismatch in DR, performed class1,11 DSA with high MFI and the RIS > 17, high risk of rejection and poor graft prognosis
If yes, what is your immunosuppression plan?
Desensitization with Plasmapheresis and IVIG alone followed by ATG and triple immune-suppressive therapy (tacrolimus base with MMF, prednisolone)
Target higher tacrolimus trough, CMV prophylaxis, PJP prophylaxis, close monitor for CMV and BKV nephropathy, urinary protein
If no, would you accept another donor who is HLA compatible but ABO incompatible?
ABO‐incompatible transplantation in contrast to HLA‐incompatible transplantation, in which persistent isoagglutinin in low titer post-transplant not necessarily associated with graft injury or rejection and usually cause graft accommodation while recurrent donor‐specific antibodies often bring about ongoing rejection and chronic tissue injury
So yes, we can accept such donor with monitor the anti B/A abs and decision of desensitization based on the isoagglutinin titer pre transplant with close monitor post transplantation
If no, would you accept another donor who is ABO compatible but HLA incompatible?
Yes, we can accept such offer but again we need to know the FXCM and CPRA% and the DSA type and level to determine the immunological risk and the need of desensitization prior to transplantation.
What are the potions available?
Search for better matched donor from nonrelated LD through paired kidney exchange program or KAS for priority access to better matched DD.
References:
1- Uchida, Junji et al. “Latest insights on ABO-incompatible living-donor renal transplantation.” International journal of urology: official journal of the Japanese Urological Association vol. 27,1 (2020): 30-38. doi:10.1111/iju.14109.
2-Bentall A, Herrera LP, Cornell LD et al Differences in chronic intra graft inflammation between positive crossmatch and ABO‐incompatible kidney transplantation. Transplantation 2014; 98: 1089–96.
Would accept this donor?
This is a case of combined HLA and ABO incompatibility. There is 112 HLA mismatch
HLA mismatch involves one HLA -A , One HLA DR, 2 HLA DQ. DR mismatch is associated with poor graft outcomes.
There are significant DSAs against A23,DQ2,DR7 and DR53 with high MFI.
There is ABO incompatibility, with anti B titres of 1/4. This however can be managed .
So I will not accept this donor.
If yes, what is your immunosuppression plan?
As this patient is high risk so will need desensitization protocols.
Induction with ATG
Maintenance with Tacrolimus, MMF and prednisolone
Monitoring of DSA levels and protocol biopsies
If no, would you accept another donor who is HLA compatible but ABO incompatible?
I will accept a donor who is HLA compatible but ABO incompatible as HLAi is more important but will take into consideration the antibody titres. With accommodation we can have better outcomes in ABOi -transplants
If no, would you accept another donor who is ABO compatible but HLA incompatible?
I will not accept a donor who is ABO compatible but HLA incompatible., However if there is no other option then I will take into consideration the level of DSAs .I will take into consideration the result of T and B cell cross match. and mean channel shift before making a decision.
What are the options available?
To find a ABO and HLA compatible donor
Paired Kidney donation
Enrol in deceased donor programme
Reference
Adnan Sharif. Who will benefit from ABOI kidney transplantation in contemporary era. AJKD. Volume 76. Issue 5 page-607-609.
Q1. I will not accept this donor because this patient is considered as high risk due to
1. HLA miss match specially in HLA-DR locus which has a critical prognostic factor that affects graft and recipient survival. (1)
2. Multi DSAs (presence of pre-TX DSA was initially associated with the occurrence of AMR, and this condition may lead to graft loss) (2)
3. Transplantation across ABO i now is possible but need (Preconditioning treatment, such as antibody reduction and desensitization, is more intensified and complicated than that of ABOc-KT. With current protocols, the occurrence of early graft loss and AMR are not completely abolished. Overall, ABOi-KT is more expensive than ABOc-KT which may restrict its adoption in resource poor countries. (3)
Q2
If I accept this donor the patient should subjected to desensitization should be done through (Plasmapheresis, IVIG, and Rituximab).
Then Induction with r-ATG
Maintenance triple immunosuppressive regimen including Tacrolimus, MMF, steroid.
Close monitoring post-transplant needed – DSA should be monitored .
Q3
I would accept a donor who is HLA compatible but ABO incompatible, but the antibody titers should be at the acceptable level.
Q4
I will accept despite HLA i was a more important risk factor for the development of BPAR than was ABOi.
. However, desensitization efforts in patients with pre transplant ABOi or HLAi can increase infection-related mortality during the early post-transplant period. The results of this investigation suggest that in patients who are at high immunological risk, such as HLAi or ABOi patients, it is necessary to both prevent acute rejection and attempt to decrease infection-related complications. (4)
Q5
1.looking for new donor with better HLA match and compatible blood group
2.paired exchange donation
3. Deceased donor
REF:
1.What is the impact of human leukocyte antigen mismatching on graft survival and mortality in renal transplantation? A meta-analysis of 23 cohort studies involving 486,608 recipients
BMC Nephrology volume 19, Article number: 116 (2018) Cite this article
4533 Accesses
2. The impact of pretransplant donor-specific antibodies on graft outcome in renal transplantation: a six-year follow-up study
Elias David-Neto,I Patricia Soares Souza,I Nicolas Panajotopoulos,II Helcio Rodrigues,II Carlucci Gualberto Ventura,I Daisa Silva Ribeiro David,I,,III Francine Brambate Carvalhinho Lemos,I Fabiana Agena,I William Carlos Nahas,I Jorge Elias Kalil,II and Maria Cristina Ribeiro CastroI
I3. ABO incompatible renal transplants: Good or bad?
Masaki Muramatsu, Hector Daniel Gonzalez, Roberto Cacciola, Atsushi Aikawa, Magdi M Yaqoob, and Carmelo Puliatti
4. Clinical outcomes of ABO- and HLA-incompatible kidney transplantation: a nationwide cohort studyEun Jeong Ko,Ji Hyun Yu,Chul Woo Yang,Byung Ha Chung,the Korean Organ Transplantation Registry Study Group
First published: 11 May 2017
https://doi.org/10.1111/tri.12979 Citations: 34
Though you touched all the aspects but need to organise the answer
thankyou DR sharma some times during typing some mistakes occurs
and some words missed will be careful next times
· Would accept this donor?
This case pertains to combined ABO incompatibility and HLA incompatability.
Although the anti-B antibody titres are 1:4 in this patient (suggesting relatively easy to cross the ABO barrier), there are other issues in this donor-recipient pair.
No. I will not accept this donor.
Reasons:
1) Degree of HLA mismatch: There is 2 DR mismatch in this case, which is associated with poor graft outcomes. Even a single DR mismatch has poor graft outcomes and hence should be avoided. (1,2)
2) Presence of DSA: DSA against both class I and class II, with high MFI, are present in this case. The DSA-RIS score is > 17 (5+5+5+10 = 25), hence it would not be prudent to use desensitization in this patient. (3)
· If yes, what is your immunosuppression plan?
This patient should not be desensitized and transplanted due to high immunological risk.
If we do take up this patient for transplant then the patient will require desensitization with Plasmapheresis and IVIG to achieve a negative crossmatch before proceeding with the transplant.
The anti-B antibody titres will also go down due to the plasmapheresis and IVIG.
Injection Rituximab 200 mg IV 2 weeks prior to the tentative date of transplantation.
Since this patient is a high immunological risk category patient, the patient will require induction immunosuppression and tacrolimus based triple drug maintenance immunosuppression.(4)
1) Induction therapy: Injection Anti Thymocyte Globulin (ATG) in dose of 1-1.5 mg/kg per day for 4-6 days (total dose 6 mg/kg).
2) Maintenance immunosuppression: Triple drug therapy including
a. Tacrolimus: Target trough level of 8-10 ng/ml
b. Mycophenolate mofetil (MMF): 1000 mg twice a day
c. Corticosteroids: Injection methylprednisolone 500 mg intravenous on the day of surgery, followed by tablet prednisolone 1mg/kg/day for 3 days and then 20 mg/day, to be tapered to 5 mg/day over next 6 to 8 weeks.
Steroid-free regimen should not be used in this case.
CMV and pneumocystis prophylaxis should be given.
Post-transplant, patient requires close follow-up with clinical and laboratory evaluation.(4)
i) Complete blood count, urine examination and serum creatinine. Tacrolimus trough levels to be monitored.
ii) Anti-B antibody titres monitoring: daily for first 2 weeks, then twice a week for next 2 weeks.
iii) To look for proteinuria: Spot urine protein-to-creatinine ratio.
iv) DSA testing: Once in first three months, then annually or whenever there is any graft dysfunction, alteration in immunosuppression or suspicion of non-adherence.(5,6)
v) Protocol biopsy: Once in first three months.(5) If the biopsy shows features of AMR, it should be treated.
· If no, would you accept another donor who is HLA compatible but ABO incompatible?
I would accept a donor who is HLA compatible but ABO incompatible, but the antibody titres are important.
Pre-transplant maximum isoagglutinin titres have a bearing on graft outcomes, with higher titres showing poor outcomes.(7) If the titres are >1:512, the chances of successful transplantation are low and due to requirement of increased plasmapheresis, there are increased risks of infections and surgical complications due to increased bleeding tendencies. Patients with titres ≥1:256 have been shown to have increased risk of AMR. (8)
So, if the isoagglutinin titres are <1:512, ABO incompatible transplants can be taken up.
· If no, would you accept another donor who is ABO compatible but HLA incompatible?
I would accept a donor who is ABO compatible but HLA incompatible, but the level of DSA are important.
The DSA-RIS score guides us in taking up patients for desensitization and transplant.(3)
· What are the options available?
The other options available in this scenario include:
a) Change the donor to someone who is compatible (ABO and HLA)
b) Enroll in kidney paired exchange program
c) Wait for offer through the deceased donor program
References:
1) Connolly JK, Dyer PA, Martin S, Parrott NR, Pearson RC, Johnson RW. Importance of minimizing HLA-DR mismatch and cold preservation time in cadaveric renal transplantation. Transplantation. 1996 Mar 15;61(5):709-14. doi: 10.1097/00007890-199603150-00007. PMID: 8607172.
2) Shi X, Lv J, Han W, Zhong X, Xie X, Su B, Ding J. What is the impact of human leukocyte antigen mismatching on graft survival and mortality in renal transplantation? A meta-analysis of 23 cohort studies involving 486,608 recipients. BMC Nephrol. 2018 May 18;19(1):116. doi: 10.1186/s12882-018-0908-3. PMID: 29776389; PMCID: PMC5960106.
3) Sethi S, Choi J, Toyoda M, Vo A, Peng A, Jordan SC. Desensitization: Overcoming the Immunologic Barriers to Transplantation. J Immunol Res. 2017;2017:6804678. doi: 10.1155/2017/6804678. Epub 2017 Jan 3. PMID: 28127571; PMCID: PMC5239985.
4) Kidney Disease: Improving Global Outcomes (KDIGO) Transplant Work Group. KDIGO clinical practice guideline for the care of kidney transplant recipients. Am J Transplant. 2009 Nov;9 Suppl 3:S1-155. doi: 10.1111/j.1600-6143.2009.02834.x. PMID: 19845597.
5) Tait BD, Süsal C, Gebel HM, Nickerson PW, Zachary AA, Claas FH, et al. Consensus guidelines on the testing and clinical management issues associated with HLA and non-HLA antibodies in transplantation. Transplantation. 2013 Jan 15;95(1):19-47. doi: 10.1097/TP.0b013e31827a19cc. PMID: 23238534.
6) Crespo M, Zárraga S, Alonso Á, Beneyto I, Díaz Corte C, Fernandez Rodriguez AM, et al; GREAT Study Group and Spanish Network for Research in Renal Diseases (REDINREN, RED16/0009). Monitoring of Donor-specific Anti-HLA Antibodies and Management of Immunosuppression in Kidney Transplant Recipients: An Evidence-based Expert Paper. Transplantation. 2020 Aug;104(8 Suppl 2):S1-S12. doi: 10.1097/TP.0000000000003270. PMID: 32658025.
7) Shimmura H, Tanabe K, Ishikawa N, Tokumoto T, Takahashi K, Toma H. Role of anti-A/B antibody titers in results of ABO-incompatible kidney transplantation. Transplantation. 2000 Nov 15;70(9):1331-5. doi: 10.1097/00007890-200011150-00011. PMID: 11087148.
8) Lee KW, Park JB, Oh DK, Na BG, Choi JY, Cho WT, Lee SH, Park HJ, Cho D, Huh WS, Kim SJ. Short-Term Outcomes of ABO-Incompatible Living Donor Kidney Transplantation With Uniform Protocol: Significance of Baseline Anti-ABO Titer. Transplant Proc. 2016 Apr;48(3):820-6. doi: 10.1016/j.transproceed.2016.01.027. PMID: 27234744.
Excellent Amit as always
Cannot agree more.
It is not recommended to accept this donor, since the risk of graft rejection is too great. There is also a significant HLA mismatch present, which is associated with high levels of MFI demonstrating a large number of donor antibodies, most likely the T and B Flow crossmatch is positive with high MCS. In addition, the ABO is incompatible.
When comparing HLA-i with ABO-i, it was shown that HLA-i was a more significant risk factor for AMR. and the patient has both.
If you answered yes, what is your immunosuppressive strategy?
The following protocols are used: rituximab (a single dose given 2 weeks to 1 month before transplant, 500 -1 gm), plasmapheresis (4-5 sessions) with IVIG.
until crossmatch is negative then proceed for transplantation with close monitoring of DSA and protocol biopsy.
– ATG is used to initiate the process.
– Triple immunosuppressive therapy (Tac, MMF, and prednisolone).
If you say no, would you be willing to accept another donor who is HLA compatible but ABO-incompatible as a replacement?
Yes
HLA-i, on the other hand, is a substantial risk factor for the development of AMR, in contrast to ABO-i. This shows that HLA-i is more important for rejection than ABO incompatible. provided that there is no other option for the recipient, like a paired exchange.
If you say no, would you be willing to accept another donor who is ABO compatible but HLA incompatible as a replacement?
I will not accept this high DSA against classes 1and 2 without knowing the result of T and B crossmatch and MCS. as the risk of rejection is still high.
Excellent, BUT using ATG and Rituximab is associated with an increased risk of infection. Can you look for a study that addressed ABOi and HLAi?
No patient with both ABOI AND HLAi which put him in high risk of ABMR
and will initiate a viscous cycle of sensitization and rejection , if this his first
transplant ,reducing his chances of future retranslation.
incompatible?
Here the risk is less than having both HLAi and ABOI. We can desensitized the patient
before transplant and pursue the plan.
Here the risk is less than having both HLAi and ABOI. We can desensitized the patient
before transplant if his DSA MFI within acceptable range not as high as in our patient.
Wait for suitable donor.
PKD.
DDA
Thank you, what is meant by DDA?
Please explain the abbreviations
SORRY ;Deceased donor
1-Kong JM, Ahn J, Park JB, et al. ABO incompatible living donor kidney transplantation in Korea: highly uniform protocols and good medium-term outcome. Clin Transplant 2013; 27: 875.
Wiley Online LibraryCASPubMedWeb of Science®Google Scholar
Thank you
References:
Thank you
1.No I wouldn’t accept this donor,because the donor is-ABOi
-DSA present against HLA class-1 and 2
-DR mismatch
Hence,very high chance of hyperacute rejection,acute rejection.
2.If any way accepting this donor then has to undergo desensitization with plasmapheresis and ivig to become crossmatch negative, then to induce with ATG and maintain on triple immunosuppression.
3.yes I would accept HLA compatible but ABOi,where i hv to cross one immunological barrier of ABOi where on longterm accomodation will be there and outcome is comparable with ABOc.
4.ABOi is better than HLAi,as more rejection is a/w HLAi tx than ABOi and graft and patient outcome are better .
5.KIDNEY PAIRED DONATION
Thank you
3. A 34-year-old CKD 5 patient received an offer from his sister (36-year-old), 112 mismatch, blood group incompatible (donor is blood group AB, the recipient is blood group A, with anti-A antibody titre of 1/4). The recipient has DSAs (anti HLA- A23 with MFI 7350, anti-DR7 with MFI 5646, anti-DQ2 with MFI 8781 and anti-DR53 with MFI 20128).
Would accept this donor?
A nationwide cohort study of a total of 1964 renal transplants to see the impact of anti-A/B & HLA-DSA antibodies on the outcomes in recipients:- The patients were classified into 4 groups:
i. Transplants from ABO-i donors (n = 248)
ii. Recipients with HLA-DSA (n = 144)
iii. Transplants from combined ABO-i & HLA-i donors (n = 31)
iv. Control group for whom neither ABO-i nor HLA-i was applicable (n = 1541).
Results were as follows:
– BPAR was higher in the HLA-i & ABO-i + HLA-i groups vs control group. In contrast, it was not higher in the ABO-i group.
– Death-censored graft survival rates did not differ across the 4 groups.
– Patient survival rate was reduced in ABO-i & ABO-i + HLA-i groups, with infection being the most common cause of death.
– Desensitization therapy because of ABO-i or HLA-i was independent risk factors for patient mortality.
– HLA-i was a more important risk factor for BPAR compared with ABO-i.
– Pretransplant desensitization for either ABO-i or HLA-i significantly increased the risk of infection-related mortality.
So the decision to proceed or not will depend on striking a balance between the above results, the availability of alternative chances of transplantation & the risk of staying on the waiting list for a compatible donor which might never come.
=============================================
If yes, what is your immunosuppression plan?
– Desensitization protocol consisting of rituximab (a single dose 2 weeks to 1 month prior transplant,100 to 375 mg/m2) & PP(with 5% albumin or FFP)with or without IVIG.
– Induction with ATG
– Maintenance triple IS(Tac, MMF & prednisolone)
– Prophylaxis for PJP & CMV infection
================================================
If no,would you accept another donor who is HLA compatible but ABO incompatible?
Yes
In contrast to ABO-i, HLA-i is a significant risk factor for the development of BPAR. This suggests that HLA-i is more significant for rejection.
However, both ABO-i & HLA-i are significantly associated with early patient mortality, mainly because of infections associated with pre-transplant desensitization therapy.
================================================
If no, would you accept another donor who is ABO compatible but HLA incompatible?
Yes, if no other alternatives are available; as the risk of HLA-i alone is less than that of combined HLA- & ABO-i.
===============================================
What are the options avialable?
Paired kidney donation
Combined PKD & desensitization
Wait for a compatible deceased donor which might never come.
Reference
Eon Jeong Ko, Ji Hayun Yu, Chul Woo Yang, et al.Clinical outcomes of ABO- and HLA-incompatible kidney transplantation: a nationwide cohort study
First published: 11 May 2017 https://doi.org/10.1111/tri.12979
Do you think that this nationwide study is enough evidence?
In which nation !? Is it applicable to your setting?
Korean Organ Transplantation Registry Study Group.
A good sum of study population.
The results of this study could be extrapolated to other settings with similar populations and resources.
It might not be applicable to a low resource setting like ours.
Thank you Mohamed
I agree with you regarding the use of ATG without Rituximab in this case. The combination carries an increased risk of infection. Very impressed
Would accept this donor?
No, the risk for graft rejection is too high. In addition to the ABO mismatch, there is an important HLA mismatch associated with high levels of MFI showing plenty of donor antibodies.
Added to this, we can sensitize the patient even more, hindering his future in the organ donation program.
If yes, what is your immunosuppression plan?
I would not procceed
If no,would you accept another donor who is HLA compatible but ABO incompatible?
Yes, the patient has low levels of B lymphocytes for his ABO incompatibility, making it possible to carry out a desensitization program (PE + IVIG and assess need for rituximab) and measurement of titration levels.
If no, would you accept another donor who is ABO compatible but HLA incompatible?
Not. In addition to being highly sensitized, patients have mismatches for HLA 1 and 2, increasing both acute and chronic rejection levels. The high levels of DSA are noteworthy, with MFI above 5000 in more than four antibodies (one of them reaching 20000).
What are the potions avialable?
Kidney paired exchange
Wait for a more compatible deceased donor
REASONABLE
Would accept this donor?
I would not accept as it will associated with high risk of graft rejection and poor graft and patient survival specially with combination of both ABOi KTX and HLA DSA antibodies (1).
-Matching 2 over 6 , with two mismatch for DR.
-HLA class I and II DSA with significant high MFI.
If we proceed ,we will lose the living and related advantages related to graft and patient survival with these high immunological factors.
If yes, what is your immunosuppression plan?
I think better try to avoid transplantation for this pairs ,if the accept after explanation the highly risk situation for the graft and patient survival.
So check CXM.
We will desensitize with (PEX ,I VIG, Rituximab protocol)
If FXCM came negative and already anti-B antibody titer is low will use induction therapy in the form of ATG and tacrolimus based therapy as maintained therapy.
We will follow the DSA and isoagglutinin antibody titers every other day in the first week post-transplant period then two to three times per week for the first month post-transplant, weekly for months 2nd and 3rd post-transplant, and then yearly after that if rising we may need another session of PEX.
If no, would you accept another donor who is HLA compatible but ABO incompatible? If no, would you accept another donor who is ABO compatible but HLA incompatible?
Nothing static and we can not take the decision alone because also we depend on center facility and patient Autonomy.
Again better for living related transplantation to be with good matching without HLA DSA antibodies and ABOc transplantation.
But If we try to choose between two options .(the two options sure better than combination of ABOi and HLA incompatible),each one has its up and downsides.
Pt with HLA compatible surely associated with good graft and patients survival with low incidence of ABMR(2).
We can prefer it if ABOi associated with low issoglutinn titer.
ABOi-ktx can be accepted with HLA incompatibility but associated with a higher risk of 1-year mortality , 3-year mortality , 5-year mortality, but not of 8-years or more mortality.(3).
What are the potions available?
Paired Exchange Kidney program which I think it’s the best option for this situation looking for ABOc ,well matched donor with no HLA DSA for good graft and patient survival.
Deceased donor kidney.
References:
1. 1- Kwon H, Kim JY, Kim DH, Ko Y, Choi JY, Shin S, et al. Effect of simultaneous presence of anti-blood group A/B and -HLA antibodies on clinical outcomes in kidney transplantation across positive cross-match: a nationwide cohort study. nature scientific reports. (2019) 9:18229.
2. Kim, J.J., Fuggle, S.V. & Marks, S.D. Does HLA matching matter in the modern era of renal transplantation?. Pediatr Nephrol 36, 31–40 (2021). https://doi.org/10.1007/s00467-019-04393-6.
3. Florian G Scurt, Lara Ewert, Peter R Mertens, et al(Clinical outcomes after ABO-incompatible renal transplantation: a systematic review and meta-analysis)April 18, 2019DOI:https://doi.org/10.1016/S0140-6736(18)32091-9.
Agree
▪︎Would accept this donor?
I will not accept this donor, the recipient is considered very high risk better to find more compatible donor.
There are multiple risk factors for hyperacute and acute rejection;
ABO incompatibility
there is a very high titre of DSAs against both HLA class I and II,
2 mismatch at DR with high MFI to DR and DQ which is associated with AMR and poor outcomes.
▪︎If yes, what is your immunosuppression plan?
Very aggressive immunosuppression is needed to over come all these risk factors
Desensitization with Plasmapheresis, IVIG, and Rituximab until negative crossmatch.
As he is very high risk patient so induction with ATG plus intraoprative methylprisnesilone
Maintenance on triple immunosuppression Tac keep trough level 8-10 ng/ml, MMF, steroid.
Follow up of DSA in the first 2 weeks then at 1,3,6,and 12 months and protocol biopsies to detect early AMR.
follow up of isoagglutinin titers weekly in the first 3 months , then every visit in the first 2 years with close follow up of graft function
▪︎If no, would you accept another donor who is HLA compatible but ABO-incompatible?
HLAi was a more important risk factor for BPAR compared with ABOi. However, pretransplant desensitization therapy for either ABOi or HLAi significantly increased the risk of infection-related mortality.
So I accept another donor who is HLA compatible with desensitization and ATG for Induction
▪︎If no, would you accept another donor who is ABO compatible but HLA incompatible?
HLA incompatible transplantation associated with higher risk of rejection it depends on the degree of mismatch but its not contraindicated but needs aggressive immunosuppression and desensitization till negative crossmatch before transplant and Induction with ATG or Alematuzamab.
▪︎What are the options available?
Paired Kidney Donation Program
No, I will not accept, this is a live donor with HLA mismatching, ABOi, with class I and II DSA with high MFI, so there is a high risk for rejection and graft survival, in this case, is expected to be poor.
If the patient accepts the risk, desensitization is required with PP, IVIG, Rituximab, induction with ATG, and tac based triple maintenance IS with monitoring of DSA and protocol biopsy. For ABOi, follow up for anti B antibody in the first 3-4 weeks post-transplant.
I will prefer ABOi kidney transplantation, as and according to a retrospective study, HLAi transplantation is associated with a higher incidence of early hospital readmission compared to ABOi transplant.
Patients who experienced early hospital readmission experienced a greater risk of late hospital readmission and death-censored graft loss and exhibited consistently lower eGFR compared to those without early hospital readmission during the first postoperative year.
Either PKD or a deceased donor.
References:
Excellent. In such a setting, is there any specific consideration for PLeX?
Thank you
Double filtration plasmapheresis, the idea is that the second filter will return back the essential substances that had been lost through the first filter, so it will reduce the side effects of PP.
Would accept this donor?
I will not proceed with this transplant as we have both ABO and HLA incompatibility. Cumulative DSA is 41000 and specially against HLA DQ2 which leads to poor graft survival.
If yes, what is your immunosuppression plan?
I can’t proceed with this transplant so there is no question of immunosuprression protocol.
If no,would you accept another donor who is HLA compatible but ABO incompatible?
Well I might consider accepting another donor who is HLA compatible and ABO incompatible depending upon isoagglutinin titer .
I think other options are to go for PKD.
Wait for DD transplant.
Would accept this donor?
So we have an offer of potential living related donor with:
-incompatible blood groups; AB to group A with anti B antibody titre of 1:4
-HLA mismatch 112 with 2 DR mismatch
-Recipient has multiple DSAs against class I and II with significant strengths.
*Immunologic assessment of this offer is high immunological risk for rejection with iABO and preformed DSAs
Before taking decision for transplantation I have to fulfil the following:
-The first step needed is to do CDC crossmatch and FCXM>A positive CDC crossmatch is considered to be a contraindication to transplantation unless after commencement of successful desensitization for positive cross match
-The baseline isoagglutinin titer is 1:4 (the titre less than 1:8 is safe to proceed for transplantation and this is the target after desensitization)
-I think it will be a difficult mission and the right decision to decline the offer.
-If yes,will need to do successful HLA antibodies desensitization:
Desensitization protocol:
Rituximab 375 mg/m2 on days 0 and 14. With pre medications for each dose of rituximab with IV Methylprednisolone 40 mg, Acetaminophen and Diphenhydramine 50 mg IV.
IVIG 2 g/kg (maximum dose of 140 g per treatment) on days 28 and 42 with pre medications.
Repeat CDC T and B cell crossmatch and a flow cytometry T and B cell crossmatch.
Desensitization is considered successful if the patient has an acceptable crossmatch, which is defined as a negative CDC crossmatch in a ≥1:2 dilution of patient serum, a negative flow cytometry crossmatch, or a positive flow cytometry crossmatch with MCS ≤250.
If failed desensitization try other protocol of low dose IVIG and plasmapheresis.
Induction of immunosuppression will be with ATG followed by triple immunosuppression of Tacrolimus with high target trough levels,MMF and predinsolone.
Close monitoring of DSA after transplantation with graft biopsy if indicated.
If no,would you accept another donor who is HLA compatible but ABO incompatible?
-Desensitization for iABO if high isoagglutinin titre is high pre transplant is a meticulous procedure with high cost and carrying high risk of rejection,so the best option will be alternative donor with compatible ABO or PKD.
If no, would you accept another donor who is ABO compatible but HLA incompatible?
Yes I will do after assessing cPRA,DSA and cross match and procced accordingly.
patients are monitored by doing isoagglutinin antibody titers daily in post transplant period then two to three times per week for the first month posttransplant, weekly for months 2nd and 3rd posttransplant, and then yearly after that. In patients with a posttransplant isoagglutinin titer ≥1:16, a kidney biopsy and/or pre-emptive plasmapheresis should be performed, especially if there is evidence of graft dysfunction as delayed graft function or rising serum creatinine.
What about the DSA?
Sure it has to be regular monitoring of DSA post transplant
Would accept this donor?
Although anti A titre is 1/4, but other risks of AR are overwhelmed and high likely the graft will have poor outcome. SO i will not proceed with transplantation.
If yes, what is your immunosuppression plan?
I will not prefer to proceed with this transplant. I would explain high risk of rejection and if the patient is unlikely to get another donor or long waiting for transplant, i would do desensitization with PLEX, IVIG and Rituximab with ATG induction. Continue with standard maintenance therapy with TAC, MMF and prednisolone. I will closely monitor DSA post transplant and would do Kidney biopsy post transplant ( protocol Biopsy).
If no, would you accept another donor who is HLA compatible but ABO incompatible?
More and more evidences showed that ABOi transplant had comparable graft survival and patient survival compared with ABOc transplant. IF no DSA, just ABOI, I would proceed with transplant.
If no, would you accept another donor who is ABO compatible but HLA incompatible?
HLA incompatible, it is a broad term, I would like to know how incompatible the HLA incompatible is. If DSA against class 1 less than 2000 or against Class 2 less than 5000, I would proceed with transplantation. My induction agent will be ATG and standard maintenance therapy with TAC, MMF and prednisolone. I would be more vigilant in monitoring DSA and low threshold to do kidney biopsy if increasing DSA or creatinine.
What are the options available?
Paired Kidney Donation Program
Wait for the deceased donor Program.
Excellent, BUT using ATG and Rituximab is associated with an increased risk of infection. Can you look for a study that addressed ABOi and HLAi?
1. I will not accept this offer because it is full of problems. HLA DR 2 mismatch plus high MFI DSA against both HLA class I and II plus ABO incompatibility, so rejection is inevitable in spite of adding more cost and adverse effects of the drugs in process of heavy desensitization.
2. If accept this offer, at least do desensitization heavily by PEX , Immunadsorption and IVig till negative cross match, induction with r ATG and then triple maintenance with tacrolimus, prednisolone and MMF.
Post transplant PEX may be used in case of rising titer of iso agglutinin or presence of DSA
Close monitoring of DSA, iso agglutinin titers together with surveillance biopsy are crucial in this case , twice weekly early postoperative then weekly in 1 st month then monthly in following 3 months then at least quarterly in 1 st year.
3 . I think it is more safe to transplant HLA incompatible than ABO incompatible.
4 .other options …PKD or Deceased donor via KAS.
Excellent, what about rituximab?
Will you use it with ATG in this case?
It’s a high risk transplant profile ,HLA antigen mismatch is 112, with DSAs anti HLA DR antigen of 20128 MFI. Flow cytometry cross match and CDC assay was not done,it might be positive with this high titer DSAs.Furthermore ,he is ABO incompatible ,however his anti-B antibody titer is within acceptable limit,It will not be a major reason to preclude kidney transplantation,with strict follow up of Anti B antibodies post transplantation especially the early 2 post operative week.
Even if CDC and flow cytometry cross match return negative,I will accept him for transplant as a high risk with protocol consistant of rATG induction high dose 6,6 mg/kg,to be followed by Tacrolimus based immunosuppressive medications aiming at Tacrolimus trough level of 10-12 ng/ml in the first few weeks ,and then 7 to 9 for the fist 6 months.I would advice Anti viral CMV and BKV,and anti fungal prophylactic PJP and Candidiasis.
If CDC and flow cytometry cross match are positive,then will advice inrollment in PKD programs which would improve the chance of having life kidney donation.
Other wise we can refer him to KAS looking for acceptable antigens.
Lastly if there is no chance to proceed ,Desensitization programs can be adopted for this high risk patient .Desensitization and PKD can be combined as well to enhance the immunogenecity profile .
Reference:
N.Krishnan et al.
HLA Antibody incompatible Renal Transplantation: Long-term outcomes similar to Decesead Donor transplant.Transplantation .August 2021.
Excellent, what about rituximab?
Will you use it with ATG in this case?
If flow cytometry cross match and CDC assay are positive(I think they are positive with this high MFI ), as RIS is more than 17 and if MCS less than 250, then will recommend desensitization protocol , including Rituximab .
Would accept this donor?
The decision to transplant this patient or not will depend on addressing the risk factors related to this transplantation:
I will not accept the donor due to high immunological risk because of cumulative DSA of 41000MFI and DSA against both class I and II, RIS >25, HLA mismatches, and specifically 02 HLA DR mismatches which are associated with the worst outcome. Also, there is ABO incompatibility. All are associated with increased risk of ABMR and TCMR and hyperacute rejection and poor graft and patient survival.
If yes, what is your immunosuppression plan?
I will not transplant this patient-if ever being considered then the patient needs aggressive management to get a negative crossmatch before transplant.
Desensitization should be done with all three modalities i.e., Plasmapheresis, IVIG, and Rituximab
Induction with r-ATG
Maintenance triple immunosuppressive regimen including Tacrolimus, MMF, steroid.
Post-transplant PLEX if isoagglutinin antibody titers high
Close monitoring post-transplant needed – DSA should be monitored once in the early post-transplant period (first 3 months) , then every 3 months till 2 years post-transplantation the annually
Regular monitoring of kidney function tests with protocol biopsies
Monitoring of isoagglutinin titers daily till discharge from the hospital, then 2-3 times per week for the first month then weekly till 3 months post-transplant then annually
If no, would you accept another donor who is HLA compatible but ABO-incompatible?
If no, would you accept another donor who is ABO compatible but HLA incompatible?
I would prefer transplant HLA compatible but ABO-incompatible –Although the risk of ABMR and worst graft survival is documented with both but less experience is available to manage ABO-incompatible transplant.
What are the options available?
Paired Kidney Donation Program
Wait for the deceased donor Program.
REFERENCES:
1- Tobian AA, Shirey RS, Montgomery RA, et al. ABO antibody titer and risk of antibody-mediated rejection in ABO-incompatible renal transplantation. Am J Transplant. 2010 May;10(5):1247-53.
2-Handbook of Kidney Transplantation sixth edition
Excellent and confident
• Would accept this donor?
The donor has multiple risk factors to have hyperacute AMR. First, the HLA mismatch (4 mismatches) and preexisting DSAs with high titers, and RIS of 25 (>17), and second, the ABO incompatibility.
So if we assume that the patient is ABO compatible based on the low titer of isoagglutinin and assuming that the donor has A2 blood group, the recipient has a high risk of hyperacute rejection if not adequately desensitized. But if no alternative donor, I would accept the donation with desensitization protocol and induction/maintenance therapy compatible with his high risk.
• If yes, what is your immunosuppression plan?
Desensitization therapy would include plasmapheresis, IVIG + rituximab to hit the double sensitization (DSA and ant-ABO isoagglutinins) followed by induction with r-ATG and triple immunosuppression CNI based.
• If no, would you accept another donor who is HLA compatible but ABO incompatible?
ABO incompatible donation was shown to have same survival and graft survival on the long term. But, patient with HLA incompatible was shown to have risk of de novo DSA, risk of AMR and poorer graft survival.
So. I would prefer ABO incompatible with low titers on HLA high mismatch, especially in the presence of anti-HLA DSA.
• If no, would you accept another donor who is ABO compatible but HLA incompatible?
If the donor and recipient are ABO compatible, HLA incompatible has been associated with poor graft and survival outcomes. The higher the mismatch, the poorer the outcome.
What are the potions available?
Alternative options are Paired Exchange Kidney program and deceased donor kidney
As decision maker would you transplant this patient?
Remember as practicing nephrologists we need to practice decision taking whatever differences we have with others and even literatures and papers provided we give our reasons and justifications for our decisions
If I have to be the decision maker, I will not proceed with this transplantation, as we have both ABO and HLA incompatibility along with DSA.