# Advantage of ABOi-KT
Reduce the waiting list and time
Expanding living donor pool
Improvement of patient’s prognosis
Excellent graft survival (comparable with ABOc-KT)
A2 blood group may be less likely to suffer antibody rejection in the presence of anti-A antibody. In fact, non-A recipients receiving kidneys from A2 donors, can universally and safely accept the transplantation without preconditioning at times of KT
Plasmapheresis (PP)and splenectomy were performed to reduce (anti-A/B) antibody and to minimize the risk of hyper acute humoral rejection. Splenectomy has been totally abandoned and the various desensitization protocols in use are combinations of antibody removal by (PP) or (IA), (IVIG) to neutralize preformed antibodies, B lymphocyte depletion by anti-CD20 monoclonal antibody (RIT) and standard triple immunosuppression (CNI; MMF; and steroid). Recently, they reported successful outcomes of ABOi-KT without RIT and splenectomy.
ACCOMMODATION
Without adequate anti-A/B antibody reduction and desensitization before KT, an incidence of AMR and irreversible damage cannot be avoided. Successful ABOi-KT requires the reduction of anti-A/B antibody titers against ABO antigens on the graft at the time of KT. However, anti-A/B antibody titer returns to the baseline level within almost 1 wk after KTeven if optimal desensitization is performed.
# Disadvantage of ABOi-KT
Comparative high immunological risk
Higher incidence of acute AMR
Intensified immunosuppression
Antibody depletion therapy
Increasing expenditure
Higher incidence of infection, the infection rate in ABOi-KT is significantly higher than in ABOc-KT (60% vs 29.8%).
Malignancy It is generally accepted that immunosuppression is associated with an increased incidence of malignancy in KT recipients compared to the general population. However, several studies have demonstrated that ABOi-KT did not
increase the risk of posttransplant malignancy compared with ABOc-KT.
Assafi Mohammed
2 years ago
ABOi kidney transplantation is favorable for the followings:
· ABOi-KT has led to an expanded donor pool and reduced the number of patients with ESKD awaiting deceased kidney transplantation (KT) .
· ABOi-KT outcome is comparable to ABO compatible KT (ABOc-KT).
· There has been an evolution in ABOi- KT leading to a simplification of protocols over the last decade and this may help reducing the cost of desensitization and pre-transplant treatment.
· Accommodation phenomenon has been noted in ABOi transplantation, whereby graft rejection is avoided despite reemergence of incompatible antibody.
ABOi transplantation; the demerits
· The cost of pre-transplant management.
· The risk of infection associated with desensitization and intensive immunosuppression.
· The risk of early hemorrhage.
Alyaa Ali
2 years ago
Is it good or bad ? why
It has some advantages and some disadvantages Advantages
Reducing waiting list and time patient with ESKD
If the patient with ESKD has an ABO incompatible living donor, the patient can chose one of three options: (1) stay on the waiting list for deceased donor KT; (2) have paired kidney donor exchange (PKDE); or (3) undergo ABOi- KT.
Expanding living donor pool
Improvement of patient’s prognosis
Excellent graft survival (comparable with ABOc-KT)
The outcome of graft survival inABOi-KT has been similar to ABOc-KT.
Disadvantages
Comparative high immunological risk
Higher incidence of acute AMR
There is an increased risk of AMR in ABOi-KT due to anti-A/ B antibody. Protocol biopsies at 3 mo posttransplant in ABOi-KT had a significantly higher incidence of AMR
compared to ABOc-KT. However, there was no significant difference in the rate of acute cellu- lar rejection between ABOi-KT and ABOc-KT
Intensified immunosuppression, as the patient at high immunological risk for rejection
Antibody depletion therapy with its risk
PE removes not only anti-A/B antibody, but also coagulation factors and anti-viral/-bacterial immunoglobulin. Consequently, the risk of bleeding and infection is increased.
Significant amounts of albumin are lost by DFPP, and almost always albumin is needed as the replacement fluid. DFPP is also removes variable amount of fibrinogen.
Increasing expenditure
ABOi-KT is more expensive than ABOc-KT because of requirement for desensitization andremoval of anti-A/B antibody.However, despite more expensive, ABOi-KT is still more cost-effective than dialysis in the long-term and has a better quality of life.
Higher incidence of viral infection
The infection rate in ABOi-KT is significantly higher than in ABOc-KT (60% vs 29.8%) . The rates of in fection including cytomegalovirus (CMV), herpes simplex virus, varicella zoster virus and BK virus (BKV)
Last edited 2 years ago by Alyaa Ali
Balaji Kirushnan
2 years ago
Blood group compatibility was once considered a necessity for renal transplant. Now a days ABO incompatible transplant as equal rates of success as compared to normal blood group transplant. It started with Japan and then worldwide different protocols are present to make this transplant a success.
Advantages:
The patients get transplanted faster rather than remaining on the waitlist. The Living donor pool is also increased by this technique and more live transplants can be encouraged. ABOi transplants increase the likelihood of transplants by 30%. The patients definitely show a survival advantage as compared to waiting on dialysis.
Disadvantages:
Patients need more immunosuppression for anti A/B titre removal. There is more incidence of viral infections like CMV/EBV. There is more incidence of AMR as compared to ABOc transplants (17.1% vs 1.5%).However the rates of TCMR are similar.. Patients are predisposed to more sepsis episodes as plasmapheresis removes normal immunoglobulins also. The studies do not show an increased incidence of PTLD, but further data is needed..
In conclusion, if no suitable blood group compatible donor is available, it is best to to convince the family for an ABOi renal transplant given the improved survival rates and less toxic desensitization protocols especially if the Anti A/B titre <1:512 and Blood group A2.
MICHAEL Farag
2 years ago
Actually, it is not the matter of good or not. Every treatment has certain risks but the decision is based on the need of this treatment. since Kx is the best modality of RRT for patients with ESRD so waiting for ABOc tx will increase the waiting list. The studies showed ABOi tx with good selection of the donor and good desensitization protocol with post kidney transplant good follow up protocol along with good Is regimen is better than remaining on dialysis waiting for ABOi. Hence, with above mentioned good protocol, still there is risk of ABOi including AMR, infection, high risk of bleeding.
Mohamed Essmat
3 years ago
The advantages of ABO incompatible transplants include:
-Increasing the number of the available donors which is still better than remaining on dialysis .
The disadvantages of ABO incompatible transplants include :
-These transplants have a higher level of immunological risks than ABO compatible transplants.
But still this is a better option under certain circumstances than waiting for a deceased donor kidney or a better matching living donor .
ABOi KT is a good option for high risk patient rather to keep the patient on Dialysis
advantages :
Reducing waiting list and time.
Expanding living donor pool .
Improvement of patient’s prognosis.
Disadvantages of ABOi-KT :
it is considered high immunological risk.
More costly
Higher incidence of acute AMR .
Intensified immunosuppression .
Higher incidence of infection.
Jamila Elamouri
3 years ago
it is good because:
1- It increases the living donor pool
2- Reduces the number of patients on the waiting list and reduces the waiting time to receive kidney transplantation.
3- Improve the prognosis of the patients
4- It has comparable graft survival with ABOc-rTx
It is bad because of:
1- It carries high immunological risk
2- Has a higher incidence of acute AMR.
3- More cost
4- Powerful immunosuppression use
5- Pharesis treatment that requires trained staff and more expenditure with more adverse effects
6- Higher incidence of infection and malignancy
7- No universal protocol yet for pre-transplant desensitization.
8- No universal accepted cut point for isoagglutinin titer.
9- Different techniques for isoagglutinin assay.
10- C4d staining can not be used as a marker for ABMR.
Wee Leng Gan
3 years ago
General overview for ABO incompatible renal transplants.
The advancement of intensified immunosuppressive protocol has increased successful ABO incompatible kidney transplantation (ABOi-KT) in the recent years. However, there are few concerns regarding residual immunological risks which might lead to allograft damage. This article focus on the transitional outcomes alongside current and future prospects in ABOi-KT.
Pre transplant management consist of antibody measurement by using either tube technique, gel technique and flow cytometry , B-Cell depletion and antibody depletion.
Assessment of anti-A/B antibody titer is essential in ABOi-KT by assessing pre-operative severity of ABO incompatibility and thus decide on optimal duration for transplantation to proceed. Besides, antibody rebound post-transplant is an early sign for antibody-mediated rejection (AMR). High pre-operative anti-A/B IgG titers is a good predictor for AMR. Post-transplant rapid increase of anti A and anti B titers is also associated with AMR and graft loss. The acceptable antibody tires ranging between 1:4 and 1:32.
B cell depletion can be achieved either by splenectomy or Rituximab. Although the efficacy of splenectomy in ABOi-KT is debatable but it could be useful as salvage treatment for severe AMR secondary to anti-HLA antibody. On the other hand, Rituximab which is anti-CD20 monoclonal antibody cause depletion of B cell. The indications of Rituximab include ABO- and HLA-incompatible KT, treatment of AMR and post-transplant lymphoproliferative disorder. However, we should caution and monitor closely for side effects of Rituximab.
Antibody depletion include plasma exchange (PE), doublefiltration plasmapheresis ( DFPP ) and Antigen-specific immunoadsorption ( IA ) . However, PE increase risks of infection and bleeding due to non selective apharesis. On the other hands, DFPP remove selectively the immunoglobulin from plasma and requires less substitution fluid compared to PE. IA can be A/B antigen IAs or A/B non-antigen IAns (non-specific/semi-selective immunoadsorption) respectively if it removes only a specific antibody such as anti-A/B antibody or removes non-antigen-specific immunoglobulin. IAs is most utilized method in HLA incompatible/ABOi KT recipients. Hence, IAs is generally regard as the most effective and safe compare to other methods of antibody depletion.
In ABOi-KT, the indication of IVIG is recommended for recipients with low anti-A/B titer in order to avoid hemolysis and AMR after transplantation.
Current intensified immunosuppressive protocol include the usage of Rituximab without splenectomy following plasmapharesis with low dose of IV IG. Maintenance immunosuppressants are mostly triple agents which are CNI, MMF and steroid. However, choices of immunosuppressants need to be individualized by weighing risk of rejection and long term risks of oversuppressions.
Increase anti-A/B antibody titres is one of the sign of early graft loss. Acute AMR is evidence by C4d staining in the peritubular capillary (PTC) and the presence of anti-donor antibodies. However, C4d deposition without AMR was seen in 85.7% of ABOi-KT at 3 mo post-transplant. Morphologically transplant glomerulopathy (TG) at 1 year after transplantation was reported as an indicator of poor outcome and graft survival. ABO incompatible grafts had a high incidence of AMR compared to ABO compatible grafts (27% vs 5.3%).However, the rejection rates in ABOi-KT were similar to that in ABOc-KT.
The points favour for ABOi-KT include reducing waiting list and time, expanding living donor pool, Improvement of patient’s prognosis and excellent graft survival (comparable with ABOc-KT). On the other hands, the disadvantages of ABOi-KT include comparative high immunological risk, higher incidence of acute AMR, side effects of over intensified immunosuppression therapy, increase medical expenditure and risks of infections.
In conclusion, ABOiKT is more costly than ABOc-KT which may restrict its application in centre with poor resources. In centre whereby ABOiKT is possible, we need to personalized the preparation and follow up plan for ABOiKT recipients. The include preconditioning treatments and maintenance immunosuppressants. With good medical resources ABOiKT provide good outcome for end stage renal failure patient. However, early recognition of AMR and prompt treatment is crucial for graft survival.
Nasrin Esfandiar
3 years ago
ABOi – KT expanded the donor pool and can be performed by using desensitization protocols and its outcome is comparable with ABOc-KT in recent years.
But there is still risk of allograft damage or increased rate of infection or malignancies. Other choices are: Stay on waiting list for deceased donor KT, paired kidney donation or ABOi-KT. Presence of anti-A or anti-B Abs is an obstacle for TX of a different BG. A2 Ag is weaker and is the subtype for 20 % of cases. A2 kidney can be safely transplanted to a non -A recipient. To perform ABOi-KT, there common principles are:
(1) Ab measurement: acceptable titer at the time of TX varies between 1:4 and 1:32
(2) B cell depletion: Rituximab has replaced splenectomy in ABOi – KT which Binds to CD20 and causes B cell depletion.
(3) Ab depletion by DFPP, IA or PE.
IVIG is usually administered after PE.
· Accommodation:
After one week after ABOi-KT, Anti-A / B Abs returns to baseline.
Accommodation is a phenomenon in which AR is avoided despite incompatible Abs. Presence of C4d alone in ABOi-KT is not an indicator for AMR. TG after first year shows poor outcome.
There is a significant increase in acute rejection in ABOi-KT and there is need for protocol biopsies. The infection rate in ABOi-KT is significantly higher. CMR, HSV, VZV and BKV rates were higher in ABOi-KT.
ABOi-KT is a cost-effective option than dialysis but more expensive than ABOc-KT. So, different conditions of patients or TX centers are effective regarding this kind of Treatment.
Mohammed Sobair
3 years ago
Its good option for high risk patient.
ABOi-KT is still more cost-effective than dialysis in the long-term and delivers a better quality of life.
advantage:
Pro ABOi-KT :
Reducing waiting list and time.
Expanding living donor pool .
Improvement of patient’s prognosis.
Excellent graft survival (comparable with ABOc-KT)
Contra ABOi-KT :
Comparative high immunological risk.
Higher incidence of acute AMR .
Intensified immunosuppression .
Antibody depletion therapy.
Increasing expenditure.
Higher incidence of viral infection.
Filipe prohaska Batista
3 years ago
Undoubtedly, it is an excellent way to include several patients who are waiting for a more compatible deceased donor. The American program itself describes the possibility of transplanting a third of the waiting list that was previously expected for compatibility. Blood type O, historically considered to have the worst prognosis for having both A and B antibodies, increases your opportunity for more compatible live donors.
Mahmud Islam
3 years ago
ABOi Renat transplantation is good as the last chance for patients in whom the transplantation is better than remaining on dialysis. It is not practised in many countries because of being expensive. the advantage is the reduction of waiting time affecting health status and decreasing the mortality related to dialysis itself and sensitization etc.
Ahmed Omran
3 years ago
ABOI -KT has advantages of shortening waiting time by increasing of living donors offers, better QOL and outcome compared with HD. and graft survival may be comparable to ABO C-KT on long term. However, disadvantages include risk of rebound post transplantation even with desensitization which could end by AMR and graft loss ,and complications and cost of use of aggressive immune-suppression during desensitization and treatment of acute rejection episodes.
So ,ABOI-KT can be useful if the patient does not find ABO C donor with long waiting time. It requires expertise and maneuvers of desensitization and after agreement of recipients regarding aggressive medications and its complications .
Ramy Elshahat
3 years ago
ABO-incompatible renal transplants: Good or bad?
it’s a good option for ESRD patients on dialysis but not the best option in comparison to ABO compatible kidney transplantation
why??
-regarding graft survival and patient survival there is a statistically nonsignificant difference between ABO compatible and non-compatible but associated with increased risk of infection, ABMR, the patient is exposed to more intense immunosuppression and more expensive
Mohamed Ghanem
3 years ago
Advantages:
1 Expanding the donor pool, especially for recipients on the long waiting list 2- better survival outcome in comparison to staying on dialysis (better prognosis) 3- a flexible chance for transplantation after the introduction of new protocols for reduction of A/B antibodies with a better outcome, minimizing the risk of ABMR 4-decrease time of waiting list of recipients 5-excellent graft outcome in comparison to ABOc-KT
Disadvantages:
1-high immunological risk 2-higher incidence of ABMR 3-need more Immunosuppression with more risk of infection added 4-increase cost for pre-transplant preparation for reduction of ABO antibodies titer with target less than 1/32 5-higher incidence of infection especially BKV and Pneumocystis jiroveci 6-long period for close follow up for early detection of ABMR So I think it’s good to go for ABOi-KT instead of keeping your patients on dialysis for better survival and quality of life despite our transplantation committee doesn’t allow till now for ABOi-KT also in developing countries it may be more financial burden due to the high cost of immunosuppression used in the reduction of anti A/B antibodies titers
CARLOS TADEU LEONIDIO
3 years ago
Is it good or bad and why?
Its good, because has led to an expanded donor pool and reduced the number of patients with end-stage kidney disease awaiting kidney transplantation. Despite, there is the increased the risk of hyperacute rejection, the ABO incompatible renal transplante outcome of graft survival is comparable to ABO compatible with the use current desensitization protocols. The increasing risk of infection and possibly malignancy its other problem, but the cost is the biggest constraint.
Ahmed Abd El Razek
3 years ago
Advantages
Expanded donor pool.
Reduced the number of patients with ESKD awaiting deceased kidney transplantation.
Accommodation phenomenon whereby graft rejection is avoided despite reemergence of incompatible antibody (possibly due to changes of antibody specificity, avidity, affinity and alteration of the antigen structure).
The outcome of graft survival in ABOi-KT has been similar to ABOc-KT.
The incidences of rejection, graft survival rate and function of ABOi-KT patients were compatible with these of ABOc-KT patients.
ABOi-KT did not increase the risk of post-transplant malignancy compared with ABOc-KT.
The estimated cost for ABOi-KT which was approximately 15% lower than dialysis and delivers a better quality of life.
Disadvantages
Usually intensified immunosuppressive protocols at the expense of increasing risk of infection and possibly malignancy.
Desensitization and antibody reduction therapies have increased the cost of KT.
High anti-A/B IgG titers is a predictor for AMR.
Adverse events related to B-cell depletion by Rituximab include fever, chill, headache, and nausea.
Plasma exchange has several disadvantages compared with more specific techniques because of non-selective apheresis, PE removes not only anti-A/B antibody, but also coagulation factors and anti-viral/-bacterial immunoglobulin thus, the risk of bleeding and infection is increased. The most common complication was hypocalcaemia.
ABOi-KT had more severe transplant glomerulopathy than ABOc-KT without HLA antibody at 1 year post transplant which is an indicator of poor outcome.
The infection rate in ABOi-KT is significantly higher than in ABOc-KT (60% vs 29.8%). The rates of infection including cytomegalovirus (CMV), herpes simplex virus, varicella zoster virus and BK virus (BKV) in ABOi-KT were also significantly higher than in ABOc-KT. The most common viral infection was BKV in 25% of ABOi-KT compared to only 8.5% of ABOc-KT.
The occurrence of early graft loss and AMR are not completely abolished.
Shereen Yousef
3 years ago
ABOi -KT was considered an absolute contraindication for transplantation due to risk of hyperacute rejection .
ABOi-KT is now performed increasingly all over the world which helped to increase the donor pool and reduced the awaiting time for deceased kidney transplantation (KT).
Advances in immunosuppression and desensitization protocols allowed successful ABOi-KT outcome
PKDE is an option which provides a recipient with an incompatible donor the chance to receive a compatible kidney, Advantages of PKDE are low immunological risk, avoidance of intensified immunosuppression due to desensitization, and cost effectiveness.
Although the use of ABOi-KT has increased worldwide, there are arguments against ABOi-KT as a universal treatment.
●it good or bad and why?
Advantages:
1 expand the donor pool.
2 decreases waiting time for transplantation which is associated with better outcomes as compared to patients on dialysis.
3 after advances in immunosuppression and desensitization protocols it became comparable to ABO Compatible transplantation with no difference in incidence of AMR or long-term graft survival.
4 the acceptable titer of anti-A/B antibody at the time of transplant has varied between 1:4 and 1:32 in the protocol of individual centers allowing more flexible protocol not strict to a very low titer.
Disadvantages:
1 High preoperative anti-A/B IgG titers are associated with poor long-term graft survival.
although Chung et al,described no statistically significant difference between high- (> 1:256) and lowtiter (< 1:128) at the baseline in allograft function at 6 mo after transplantation.
2 it is un clear how long the monitoring should be continued.
4 higher incidence of ABMR.
5 intensified immunosuppression with higher incidencef infection and malignancy.
6 higher cost.
7 it needs more experienced centres.
Despite these disadvantages ABOI KT is still better option than being on dialysis when no other available compatabile donor available
Abdulrahman Ishag
3 years ago
ABO incompatible renal transplants Good or bad?
Advantages;
1- Reducing waiting list and time;
Different ways have been proposed to increase the donor pool and ABO incompatible KT (ABOi-KT) represents a valid source of organs to decrease the donor waiting list.
2-Expanding living donor pool;
When a patient with ESKD requires KT and an acceptable living donor is ABO incompatible with the recipient, the patient can currently chose one of three options: (1) stay on the waiting list for deceased donor KT; (2) have paired kidney donor exchange (PKDE); or (3) undergo ABOi KT.
3-Improvement of patient’s prognosis
4-Excellent graft survival (comparable with ABOc-KT);
The outcome of graft survival in ABOi-KT has been found to be similar to ABOc-KT. In ABOi-KT, acute AMR by anti-A/B antibody is a well recognized cause of early graft loss.
Disadvantages;
1-Comparative high immunological risk;
Blood type incompatibility means the exposure of A or B antigen to a person who has antibodies against these antigens. Therefore, these antigen expressions of an organ have been obstacles for ABOi-KT . Blood group type A, however, carries A1 or A2. The expression of A2 antigen is weaker than that of A1 antigen . A2 kidney may be less likely to suffer antibody rejection in the presence of anti-A antibody. In fact, non-A recipients receiving kidneys from A2 donors , can universally and safely accept the transplantation without preconditioning at times of KT.
2-Higher incidence of acute AMR;
There is an increased risk of AMR in ABOi-KT due to anti-A/B antibody. Acute rejection in ABOi-KT was mainly AMR (73.3%) as compared to ABOc-KT without HLA antibody (12.5%). However, there was no significant difference in the rate of acute cellular rejection between ABOi-KT and ABOc-KT .
3-Intensified immunosuppression;
Is associated with increased risk of opportunistic infections . Efforts have have been made to minimize immunosuppression in order to reduce the long-term risk of over immunosuppression .
4-Antibody depletion therapy
Because of non-selective apheresis, PE re-moves not only anti-A/B antibody, but also coagulation factors and anti-viral/-bacterial immunoglobulin. Consequently, the risk of bleeding and infection is increased. he most common complication was hypocalcemia (6.8%), followed by urticaria or pruritus (4.3%), hypotension (2.9%) and nausea or vomiting (1.2%).
DFPP is designed to remove selectively the immunoglobulin from plasma and requires less substitution fluid compared to PE. Significant amounts of albumin are lost by DFPP, and almost always albumin is needed as the replacement fluid. DFPP is also removes variable amount of fibrinogen [, and its measurement is necessary to avoid bleeding complication.
IAs is selective and free from side effects of PE and DFPP. Single IAs reduces 2- to 4-fold titer between pre- and post-IAs, and at least four preoperative IAs are usually needed to obtain an acceptable titer at the expense of increased cost compared to PE and DFPP .
.
5-Increasing expenditure
6-Higher incidence of viral infection
The infection rate in ABOi-KT is significantly higher than in ABOc-KT .The most common viral infection was BKV in 25% of ABOi- KT compared to only 8.5% of ABOc-KT. However, ABOi-KT patients who were treated with RIT, may have had different infection profiles. Polyoma virus infection rate (64.3%) was relatively high in RIT. Moreover, infection related-death was significantly higher in RIT treated patients.
Malignancy ;
Several studies have demonstrated that ABOi-KT did not increase the risk of post transplant malignancy compared with ABOc-KT.
Cost of ABOi-KT;
It is recognized that KT is a cost-effective option over dialysis. ABOi-KT is more expensive than ABOc-KT because of requirement for desensitization and removal of anti-A/B antibody. The cost of ABOi-KT in the first 90 d posttransplant is $90300 compared to $52500 for ABOc-KT . However, despite more expensive, ABOi-KT is still more cost-effective than dialysis in the long-term and delivers a better quality of life.
Weam Elnazer
3 years ago
ABO-incompatible kidney transplantation: Is it a good or a negative thing?
Advantages include: -a live donor ABOi-KT is a potential alternative to waiting for a kidney transplant or being placed on a dead donor list.
– ABOi-KT has resulted in an increase in the number of potential donors.
When ABOi-KT occurs, there is a phenomenon known as accommodation, which is defined as the prevention of graft rejection despite the reemergence of incompatible antibodies.
– The outcome of graft survival in ABOi-KT has been shown to be comparable to that of ABOc-KT.
In ABOi KT, there was no increase in the risk of malignancy.
As a result, the infection rates of ABOi-KT were considerably greater than the infection rates of ABOc-KT for cytomegalovirus (CMV), herpes simplex virus, varicella-zoster virus, and BK virus (BKV), among other pathogens.
– Anti-A/B antibodies are associated with an increased risk of AMR in ABOi-KT patients. There was no statistically significant difference in the rate of acute cellular rejection between ABOi-KT and ABOc-KT, on the other hand,
-Increase the likelihood of adverse effects associated with desensitization procedures.
Treatment is more expensive than ABOc-KT because of the need for desensitization and elimination of anti-A/B antibodies; nevertheless, even though it is more expensive in the short term, ABOi-KT is more cost-effective than dialysis in the long run and provides a higher quality of life.
my opinion: ABOi should be individually evaluated and also the availability of the resources in the transplant centre is very important.
mai shawky
3 years ago
Why ABO I -KT?
Shortening of the waiting time by expansion of living donors pool
Better QOL and outcome than chronic HD.
Graft survival may be comparable to ABO c-KT over long run
Why not?
Still carry risk of rebound post transplantation in spite of desensitization which eventually ends by AMR and graft loss
Use of aggressive immune-suppressives during desensitization and treatment of acute rejection episodes add more cost and predispose patient to higher risk of infections and malignancy.
In conclusion, it can be used only if the patient does not find ABO c donor after long waiting time. It is only done in case of available expertise and maneuvers of desensitization and after acceptance of the idea of aggressive medications and possible complications by the recipients.
Asmaa Khudhur
3 years ago
Although ABOi-KT is more expensive than AB- Oc-KT because of requirement for desensitization and removal of anti-A/B antibody, It is recognized that KT is a cost-effective option over dialysis.
despite lack of control trials in ABOi-KT, more than satisfactory outcomes have been observed in adult and pediatric recipients, in many studies equivalent to living ABOc-KT.
The advantages of ABOi-KT:
Reducing waiting list and time
Expanding living donor pool
Improvement of patient’s prognosis
Excellent graft survival (comparable with ABOc-KT)
Disadvantages ofABOi-KT:
Comparative high immunological risk Higher incidence of acute AMR
Intensified immunosuppression Antibody depletion therapy
Increasing expenditure
Higher incidence of viral infection
Huda Al-Taee
3 years ago
Is it good or bad and why
Advantages:
reduce waitlist and time for transplantation.
expand the donor pool.
improve patient’s prognosis ( better than being on dialysis).
excellent graft survival as it is comparable to ABOc Tx.
no difference in the rate of TCMR at 3 months as compared to ABOc Tx.
no difference in the rate of subclinical rejection when compared to ABOc Tx.
no difference in IFTA, chronic vasculopathy and allograft function as compared to ABOc Tx.
Disadvantages:
high immunological risk.
higher incidence of ABMR.
Intensified immunosuppression.
the need for antibody depletion therapy.
increasing expenditure.
higher incidence of viral infection.
the acceptable level of antibody titer pre-transplant is variable.
no defined protocol for IS medications minimization.
more sever TG at 1 year than ABOc Tx.
it is unknown for how long the monitoring of antibody titer post-transplantation is.
Naglaa Abdalla
3 years ago
ABO incompatible renal transplants : Good or bad ?
ABO incompatible kidney transplantation(ABOi-KT) is a useful source of organs decreasing the donor waiting list after certain preoperative preparation.
If an ESRD has a donor who is ABO incompatible, there are three choices :
1- Stay on waiting list for deceased donor.
According to the Organ Procurement and Transplantation Network(OPTN) report 2011, 86500 patients on the deceased donor waiting list and almost 28000were added annually to the list in the united states. 10000 patients received deceased donor kidney transplantation and 4900received living KT.
5000 patients on dialysis died while waiting for a kidney. The median waiting time is around 4 years.
2- To have a paired kidney donor exchange(PKDE).
Here 2 or more incompatible couples of donor-recipient exchange donor to create 2 or more compatible pairs.
Started in 1980s where reported by Rapaport.
It increases donor source and decreases waiting list, has low immunological risk with avoidance of heavy immunosuppression and cost effectiveness.
3- Undergo ABOi-KT.
This first started in Japan due to the lack of deceased donors, accounted for approximately 30% of all living donor KT in Japan.
In United states only 738 cases (0.94%)were done between 1995 and 2010, the number is increasing annually.
In United Kingdom the number increased over the last decade from <10 per year to100 per year representing 1.0% of living donor transplant performance. ABO Antigens and Antibodies: Blood group O is a universal donor to all other groups.
Blood group B is a universal recipient to all other groups.
A: has A1 (dominant) and A2 antigens/ anti B antibody.
B: has B antigen / anti A antibody.
AB: has A and B antigens but no antibody.
O: has no antigens but has anti A and anti B antibodies. ABOi-KT Preoperative Management:
1- Antibody measurement: to determine the degree of operative preconditioning and the time to permit transplantation.
For post-transplant monitoring for early detection of AMR by antibody rebound.
Measurement is by tube technique, gel technique and flow cytometry.
High preoperative anti A/B IgG titers is a predictor of AMR and associated with poor long term graft survival.
The accepted titer of anti-A/B antibody is between 1:4 and 1:32 in the protocol of different centers.
2- B-cell depletion:
Either by splenectomy with many disadvantages.
Or using Rituximab which is recently replacing splenectomy.
After a comparative analysis of splenectomized recipients compared to recipient treated with rituximab without splenectomy that showed no statistically significant difference in the anti-A/B antibody titer of KT and liver transplantation, a conclusion that splenectomy was not an essential pre-transplantation treatment in ABOi-KT.
3- Antibody depletion by:
a- Plasma Exchange(PE).
b- Double filtration plasmapheresis(DFPP).
c- Immunoadsorption (IA). Use Of IVIG :
Its action is complement down regulation-interaction with Fc portion-inhibition of B/T cell proliferation- inhibition of CD8 T cell cytotoxicity- increased apoptosis of B cell.
Rare and serious side effects include renal toxicity, thromboembolic events, neurological, hematological, and dermatological toxicities.
IVIG preferable to be of low anti-A/B titer to avoid hemolysis and AMR. Currant Protocol of ABOi-KT:
Splenectomy free protocols published in the last decade, it is replaced by Rituximab.
RIT or splenectomy free protocols have successfully used low dose IVIG after plasmapheresis.
North European protocol is IA followed by high dose IVIG
In Japan 2012 Uchida et al reported use of RIT of 150mg/m2 twice at -14 and 0 d, antibody depletion by DFPP or PE, no use of IVIG and the titer should be < 1:16.
Pre-transplant immunosuppression MMF/MPS at -1mo, CYA or TAC at -3d.
Maintenance immunosuppression CYA or TAC –MMF/MPS. The Incidence of Acute cellular Rejection and Antibody Mediated Rejection in ABOi-KT:
Protocol biopsies at 3 month post-transplant in ABOi-KT had a significant higher incidence of AMR compared to ABOc-KT(17.9% versus 1.1% ) but no significant difference in ACR(48.4% versus 35.7%).
Gloor et al, Setoguchi et al, Wipler et al have reports on that.
The estimated cost for ABOi-KT over 20 years was 315600 Dolars which was 15% lower than dialysis.
So in conclusion The advantages of ABOi-KT:
Reducing waiting list and time
Expanding living donor pool
Improvement of patient’s prognosis
Excellent graft survival (comparable with ABOc-KT) Disadvantages of ABOi-KT:
Comparative high immunological risk
Higher incidence of acute AMR
Intensified immunosuppression
Antibody depletion therapy
Increasing expenditure
Higher incidence of viral infection
Reem Younis
3 years ago
ABO incompatible renal transplants: Good or bad? Advantanges :
-live donor ABOi-KT is a viable alternative to waiting on dialysis or
deceased donor list.
– ABOi-KT has led to an expanded donor pool.
-ABOi-KT is associated with accommodation which is defined as a phenomenon
whereby graft rejection is avoided despite the reemergence of incompatible antibodies.
– The outcome of graft survival in ABOi-KT has been similar to ABOc-KT.
-No increase in the risk of malignancy in ABOi KT. Disadvantages:
-The rates of infection including cytomegalovirus (CMV), herpes simplex
virus, varicella-zoster virus, and BK virus (BKV) in ABOi- KT were significantly higher than in ABOc-KT.
– There is an increased risk of AMR in ABOi-KT due to anti-A/ B antibodies. However, there was no significant difference in the rate of acute cellular rejection between ABOi-KT and ABOc-KT.
-Increase side effects related to desensitization protocols.
– ABOi-KT is more expensive than ABOc- KT because of the requirement for desensitization and removal of anti-A/B antibodies but despite being more expensive,but ABOi-KT is still more cost-effective than dialysis in the long term and delivers a better quality of life. Conclusion: I think ABOi-KT is better than waiting on deceased donor list or remaining on dialysis.
kumar avijeet
3 years ago
ABOi transplant is a mode of tx where bloodgroup barrier hasbeen crossed which was previously a contraindication, today is a possibilty which reduces waiting .
Whether it is good or bad, is definitely a difficult question to be answered.
GOOD-
1.decreases waiting time.
2.increases donor pool
3.decreases morbidity,mortality of hd,pd pts
4.better than deceased donor tx
5.comparable outcome according to ABOc
6.accomodation process is there
BAD-
1.bit of costly(desensitization)
2.more infections,malignancy(intesified
immunesuppression)
3.extra risk of rejection as ABOi.
So, three against and six in favour of ABOi, so mandate is good i think.
Amit Sharma
3 years ago
Is it good or bad and why?
The verdict regarding ABO incompatible transplants, whether they are good or bad, depends on a number of ifs and buts.
Overall, ABO incompatible is a good thing to happen to the field of transplantation as it opens up transplant opportunities for patients who do not have a blood group compatible donor.
The advantages of ABO incompatible transplants include:
1) Expansion of the available donor pool with consequent increase in transplant rates and decreased waiting times.
2) The graft prognosis is equivalent to ABO compatible kidney transplants, although with increased AMR, is a big plus point, making it worth the risks involved.
3) Getting an ABO incompatible transplant is better than remaining on dialysis with respect to patient survival as well as cost-effectiveness.
The aspects of ABO incompatible transplants discouraging their use include:
1) There is no consensus on the ideal pre-operative isoagglutinin titres as well as a standard protocol to be followed (with a number of variations being used). This can create confusion especially if a new ABO incompatible program is being set-up.
2) These transplants have a higher level of immunological risks than ABO compatible transplants, and hence have higher rates of AMR especially in patients with high baseline titres or having rapid rebound of titres. It requires intensive monitoring both pre- and post-transplant.
3) Intensive immunosuppression used as well as the antibody depletion procedures used (plasmapheresis or immunoadsorption) increase the risk of complications including infections like CMV and BK virus (more with rituximab use), HSV, Varicella zoster virus, etc and increased risk of bleeding.
4) The cost of the transplant increases due to the desensitization procedures (Plasmapheresis, IVIG, anti-CD20 antibody etc) in comparison to ABO compatible transplants.
In a nutshell:
If a recipient does not have a blood group compatible donor, is not able to get a donor through kidney paired donor program, and has lower anti-blood group antibody titres (<1:128), only then ABO incompatible transplant should be offered. This is a better option than waiting for a deceased donor kidney, especially in our setup, where the waiting times are 5-6 years.
Dear Amit I like your conclusion, it is excellent and up to the point “If a recipient does not have a blood group compatible donor, is not able to get a donor through kidney paired donor program and has lower anti-blood group antibody titres (<1:128), only then ABO incompatible transplant should be offered. This is a better option than waiting for a deceased donor kidney, especially in our setup, where the waiting times are 5-6 years”.
ABOI kidney transplant was a contraindication due to the risk of hyper acute rejection,
Japan decided to do ABOi when there is no access to DD program and they showed comparable graft survival to ABOc KTX Now, ABOI- transplantation practiced in many centers in US and Europe with acceptable outcome.
Desensitization protocols for ABOI kidney transplantation has been evolving over time, no standardized protocol across the globe but it depends on center specific protocols
ABOi TX has been divided to Antibody measurement, B cell depletion and antibody removal
Antibodies measurements:
Measurement of anti-A/anti B titers before and after ABOi transplantation is better with gel method but flowcytometry is showed to be preferred and more accurate method but limited by cost and availability . The higher antibodies titer and the rapid rebound in first two weeks associated with higher rate of AMR and graft loss . post-transplant titer monitoring is important to prevent AAMR.
B cell depletion:
B cell depletion protocols including surgical splenectomy which have been replaced by B cell depleting agent anti-CD 20 monoclonal AB, rituximab . various doses have been tried but nowadays opt to use low dose rituximab usually 10 days pre-operative with higher risk of infection like CMV, BKV, PJP.
Antibody removal
Plasmapheresis, DFPP, IA:
Conventional PP has been used but with the risk of removing coagulants, Igs, calcium together with risk of allergic and hypotension. It requires large replacement fluid in the form of human albumin or FFP. DFPP more specific which remove specific Igs and requires less replacement fluid. IA reduce the 2 -4 fold of titer but cost will be expensive.
IVIG:
have pleotropic effects including complement inhibition , FC receptors binding, inhibit B and T cells proliferation, CD8 T cell inhibition, with B cells apoptosis
No standardized dose, high dose, low dose usually given after plasmapheresis many side effects including infusion related allergic reaction, risk of thromboembolic events, AKI, its use in combination with plasmapheresis the preferred and widely used protocol with or without Rituximab.
Triple intense immunosuppression:
standard triple therapy in ABOI KTX have been moved over time from cyclosporine based to tacrolimus based with full dose MMF and prednisolone, pre transplant 2-4 weeks.
GOOD:
1)it has reduced waiting list in patient No. and time
2) Expanding living donor pool
3) Improvement of patient’s prognosis as compared to Deceased donor transplantation
4) Excellent graft survival (comparable with ABOc-KT)
5) being cost effective as compared to remaining on dialysis as RRT
BAD:
1)carries a high immunological risk
2)Higher incidence of acute AMR
3)Intensified immunosuppression which renders the patient at higher risk of infections and theoretically at higher risk of malignancies
4) mandates Antibody depletion therapy which also has its own complications especially the widely available conventional plasma exchange.
5)Increasing expenditure
6)Higher incidence of viral infection, mainly polyoma BK virus infection in those treated with Rituximab
7) still there is no clearly defined desensitization protocol for ABOi K
Accommodation
Without adequate anti-A/B antibody reduction and desensitization before KT, an incidence of AMR and irreversible damage cannot be avoided. Successful ABOi-KT requires the reduction of anti-A/B antibody titers against ABO antigens on the graft at the time of KT. However, anti-A/B antibody titer returns to the baseline level within almost 1 wk after KT even if optimal desensitization is performed. Therefore, intense monitoring is necessary during critical first two weeks after ABOiKT. Accommodation is defined as a phenomenon whereby graft rejection is avoided despite reemergence of incompatible antibody
Overall, I would like to do ABOi KT as many as I can in my center as DDK is limited due to widely religious reasons. I find ABOi KT with improved protocols and preventatives measures to infections, will lead to success
ABOi transplantion is an art , which is diffucult to some centers to do.
in this era of PKD programme , ABOi had siginficantly decreased in all centers around the globe.
The benifts of this kind of transplantion is to increase the donor pool theoritically by 30%, but in facts due to logistics issues and non trainned pyhiscians it is not.
Using very aggresive stratgies to deplete antibodies aganist both A&B antigens is hectic and costly and time consuming.
A lot of maneuvers and medications are used for in many centers with diffrent protocols , using plex, IV IG G , IA, RTX.
ABMR is the main concern post or which is very devasating which may lead early or late graft loose.
These startiges put the patient at high risk f comaplication pre and post transplantion, like catatstrophic infection with many viruses like CMV, BK, HSV, HZV, which is diffucut to treat.
i cant not say its bad or good , if there is no choice for this patient except ABOi transplantion so , we can go ahead which is better for him rather being on RRT , with good counselling about the consequences of this such hectic process.
ABO antigen and antibodies,
A,B and O antigens are polysacchccharide antigens which are found in the red cells , platelets and other tissues such as endothelium.
The Antibodies to blood group antigen are isohemagglutinins and can be either IgM or IgG.In kidney transplantation , its only IgG that is of significance.
Blood type A develop anti B anti bodies.Similarly blood type B develop anti A antibodies. While blood type AB has both A and B antigens , but no anti bodies, Blood group O has antibodies against B and A antigens and has no antigens.,
ABO incompatible patients represent a major hurdle for kidney transplantation as its associated with potential AMR. It was considered an absolute contraindication to kidney transplantation.
Blood group type A:
It carries A1 and A2.The expression of A2 antigen is weaker than A1 antigen.
A2 constitute approximately 20% of blood .
A2 kidney may be less likely to suffer antibody rejection in the presence of anti A antibodies.
Non A recipients receiving kidney from A2 donors, can universally and safely accept the transplantation without preconditioning at time of of KT.
Currently ABOi KT represent a valid source of organ to decrease the donor waiting list.
3 options are offered for ABOi :
1] KAS
2] PKD: advantages , are low immunologic risk, avoidance of intensified immunosuppression due to desensitization, and cost effectiveness.
3] ABOi KT: it has increased due to the fact that desensitization protocols has been simplified.
Current strategies of ABOi KT compose three common principles:
1] Antibody measurement:
A/B antibody titer is crucial in ABOi KT, as according to this titer effectiveness of preoperative conditioning will be assessed .similarly, post operative titer monitoring detect AMR by antibody rebound. The acceptable preoperative anti A/B level has fallen between 1/4 and 1/32.
2] B cells depletion;
Rituximab has replaced splenectomy as a strategy to deplete B cells. However , splenectomy is still often recommended in severe unresponsive cases of AMR.
3]Antibody depletion:
The antibodies depletion is the core of desensitization of ABOi transplantation. DFPP is commonly used, However ,IA has replaced PP with more efficient and less side effect , but highly expensive technique .
IVIG use:
mechanism of action:
1]complement down regulation.
2]interaction with Fc receptors.
3]Inhibit B/T cells proliferation.
4]Inhibit CD 8 T cell cytotoxicity
5]increase apoptosis of B cells.
Accommodation :
A phenomena whereby graft rejection is avoided despite reemergence of incompatible antibodies.
North Europe protocol ; IA followed by high dose IVIG, Post operative IA is not routinely performed ,but depend on Antibodies level. it was made to avoid over immune suppression and heightened risk of infection and malignancy
Maintenance immunosuppressants .
Triple agents involving CNI,MMF and Steroid.
ABOi Kidney Transplantation :
It is GOOD in that :
1)it has reduced waiting list in patient No. and time
2) Expanding living donor pool
3) Improvement of patient’s prognosis as compared to Deceased donor transplantation
4) Excellent graft survival (comparable with ABOc-KT)
5) being cost effective as compared to remaining on dialysis as RRT
On the other hand it is bad in :
1)carries a high immunological risk
2)Higher incidence of acute AMR
3)Intensified immunosuppression which renders the patient at higher risk of infections and theoratically at higher risk of malignancies
4) mandates Antibody depletion therapy which also has its own complications especially the widely available conventional plasma exchange .
5)Increasing expenditure
6)Higher incidence of viral infection , mainly polyomma BK virus infection in those treatted with Rituximab
7) still there is no clearly defined desessitization protocol for ABOi KT
Overall I think it is a good option when good preconditioning and later on follow up are feasible
Kidney transplantation is considered the best option for patients with the end-stage renal disease worldwide. Due to the shortage of translatable organs, another probable risky method was accepted for a kidney transplant, such as ABOi-KT, which expanded the donor pool & its outcome is comparable to ABOc-KT in both adults & pediatric recipients.
Although it increases the risk of infection & malignancy due to intensified
immunosuppressive protocol & increases the cost compared to ABOc-KT, it is
a good option for ABOi patients.
Alternatives to that is a waiting list for cadaveric donor KT, or paired kidney donor exchange.
ABOi-KT requires desensitization protocol, to avoid AMR , this can be done with the
current strategies:
1-antibody measurement (an excellent method is Flow cytometry ).
2- B-cell depletion ( nowadays with rituximab).
3-Antibody depletion.
Thank you What is the difference in acute rejection rate between ABOi and ABOc transplantation?
Last edited 3 years ago by Professor Ahmed Halawa
Mohamed Mohamed
3 years ago
I. ABO incompatible renal transplants: Good or bad? Is it good or bad and why? What makes ABO-I good?
– Shortage of donor pool necessitates the search for alternatives to PKD organs
– To reduce the number of ESRD on deceased donor waiting list & improve patients prognosis.
– Outcomes are comparable to ABO-c transplants
– Simplified protocols are emerging & thus increasing the usage of ABO-i transplants.
– Availability of many options for reducing anti-A/B antibody & to reduce the risk of hyper-acute rejection.
– Pre-& post- transplant anti-A/B antibody titers help prediction & early detection & management of AMR.
– Certain ABO blood types are less immunogenic & permit transplantation without the need for pre-transplant desensitization: A2 donation to non-A recipients (B & A2B). A2 present in 20% of blood type A in white races; & only 0.15% in Japanese.
– Splenectomy is largely replaced by rituximab in ABO-I transplant protocols to remove B-cell.
– In some case there is normal graft function & structure(accomodation) despite reemergence of anti-A/ B antibody against A or B antigen.
– Maintenance IS agents do not differ from those of ABO-C transplants (triple: CNI, MMF & steroid).
============================================= Adverse effects & arguments against ABO-I kidney transplantation: 1. Higher immunological risks & thus intensified IS & antibody depleting therapies compared to ABO-C transplants with its known consequences: – The infection rate is significantly higher than in ABO-c transplants (60% vs 29.8%). BKV was the most common viral infection (25% vs 8.5% in ABO-c- transplants). – Limited data indicates that ABO-i is not associated with an increasing incidence of malignancy; however long-term observations are needed.
2. Significantly higher incidence of AMR compared to ABO-c- transplants (17.9% vs 1.1%). However no significant difference in the rate of ATCMR (48.4% vs 35.7%). 3. ABO-i is more expensive than ABO-c transplant due to costs of desensitization & removal of anti-A/B antibody. It is, however, more cost-effective than dialysis in the long-term & provides a better quality of life.
In the context of living donor ,who is ABO incompatible with the recipient, the patient can chose one of three options:
(1) stay on the waiting list for deceased donor KT
(2) have paired kidney donor exchange
(3) undergo ABOiKT.
According to the Organ Procurement and Transplantation Network (OPTN) report 2011, 86500 patients on the deceased donor waiting list, Almost 5000 patients died while waiting for a kidney.
ABOi transplantation was reviewed in several studies in different countries and using different desensitization protocols and induction therapy. Overall, ABOi transplantation was shown to be similar to ABO compatible on the long term graft and patient survival with cost effectiveness when comparing to dialysis.
So ABO incompatible renal transplants is Good when other options are not available. It is associated with better survival rate when comparing to a patient receiving dialysis in the waiting list. It is Bad when it is done in a patient with high risk for infection or malignancy when paired exchange kidney program is available.
Current strategies of ABOi-KT compose three common principles: (1) antibody measurement; (2) B-Cell depletion; and (3) antibody depletion.
Antibody measurement
The acceptable titer of anti-A/B antibody at the time of transplant has varied between 1:4 and 1:32 in line with the protocol of individual centers. Inclusioncriteria for isoagglutinin titer is < 1:256, no statistically significant difference between high- (> 1:256) and low titer (< 1:128) at the baseline in allograft function at 6 mo after transplantation.
B-cell depletion
Splenectomy and Rituximab: Splenectomy has been largely replaced by RIT in ABOi-KT protocols to remove B-cell
Antibody depletion
In order to eliminate existing anti-A/B antibody, plasma exchange (PE), DFPP and IA[67] are available. They differ in their mechanisms of action, specificity, efficiency and cost.
USE OF IVIG
IVIG is believed to act through various mechanisms: (1) complement down-regulation; (2) interactions with the Fc receptors; (3) inhibit of B/T-cell proliferation; (4) inhibit of CD8 T-cell cytotoxicity; and (5) increased apoptosis of B-cell.
Accommodation
anti-A/B antibody titer returns to the baseline level within almost 1 wk after KT[11,79,80], even if optimal desensitization is performed. Therefore, intense monitoring is necessary during critical first two weeks after ABOiKT.
ADVERSE EFFECT OF ABOI-KT
Infection: The infection rate in ABOi-KT is significantly higher than in ABOc-KT (60% vs 29.8%)[37]. The rates of infection including cytomegalovirus (CMV), herpes simplex virus, varicella zoster virus and BK virus (BKV).
Malignancy
several studies have demonstrated that ABOi-KT did not increase the risk of posttransplant malignancy compared with ABOc-KT.
Cost effectiveness
It is recognized that KT is a cost-effective option over dialysis
Alaa eddin salamah
3 years ago
Article I
ABO incompatible renal transplants: Good or bad?
Advantages
Reducing waiting list and time
Expanding living donor pool
Improvement of patient’s prognosis
Excellent graft survival (comparable with ABOc-KT), it is a valid alternative therapy for ESKD
and the outcome of ABOi-KT has become equivalent to ABOc-KT in adult and pediatric recipients
Disadvantages
Comparative high immunological risk
Higher incidence of acute AMR
Intensified immunosuppression
Antibody depletion therapy
Increasing expenditure
Higher incidence of viral infection
I think it is a GOOD program for patients with no ABO compatible living donor, it is better than dialysis for sure with better outcome than deceased donor transplant and comparable results with ABOc KT. Continuing this program within certain conditions will allow more advancements in protocols for ABOi KT, I think if Japan did not take the lead in ABOi KT we wouldn’t have the knowledge we have today.
Abdul Rahim Khan
3 years ago
This review has focussed on whether ABOi- KT should be offered as a therapeutic option. Historically ABO incompatible kidney transplant- (ABOi- KT) was absolute contraindication due to risk of hyper acute rejection. Since the successful series of ABO incompatible kidney transplant has led to expansion of donor pool in short waiting list. This, however will require more extensive immunosuppression protocols. Recently the outcome of ABOi- KT is comparable to ABO compatible KT. This however involves additional risks like infections and malignancy. Cost of ABOi- KT was very high but protocols have been simplified in the last decade.
ABOi- KT will require desensitization protocols-
PLEX
IVIG
B cell depletion- Rituximab
Intense Triple immunosuppression with TAc, MMF and prednisolone
ABOi- KT- Good or Bad
Advantages
It increases donor pool thus decreasing donor W/L
Outcome of ABOi- KT is comparable to ABO compatible KT
Surgical Splenectomy has been replaced by Rituximab
Accommodation- A phenomenon in which graft rejection in avoided despite re emergence of incompatible antibodies.
Disadvantages
Higher cost
More infection risk
Risk of malignancy
Aggressive immunosuppression
Desensitisation in specialist centre and aggressivemonitoring
Higher incidence of AMR
Absence of RCTs to standardize the protocols
Usually not possible in third world countries
mohamed hefzy
3 years ago
ABO incompatible kidney transplantation (ABOi-KT) is good but with precautions and good management as ABOi-KT has led to an expanded donor pool and reduced the number of patients with ESKD awaiting deceased kidney transplantation (KT). Intensified immunosuppression and immunological understanding has helped to shape current desensitization protocols. Consequently, in recent years, ABOi-KT outcome is comparable to ABO compatible KT (ABOc-KT)
But in ABOi-KT, there is an additional residual immunological risk that may lead to allograft damage, despite using current diverse but usually intensified immunosuppressive protocols at the expense of increasing risk of infection and possibly malignancy. Notably the cost of KT is more but when compared to chronic dialysis it is less .
When a patient with ESKD requires KT and an acceptable living donor is ABO incompatible with the recipient, the patient can currently chose one of three options:
(1) stay on the waiting list for deceased donor KT;
(2) have paired kidney donor exchange (PKDE);
(3) undergo ABOiKT.
In early cases splenectomy was indicated pretransplantation but nowadays, splenectomy has been totally abandoned and the various desensitization protocols in use are combinations of antibody removal by plasmapheresis or immunoadsorption (IA), intravenous immunoglobulin (IVIG) to neutralize preformed antibodies, B lymphocyte depletion by anti-CD20 monoclonal antibody (RIT) and standard triple immunosuppression (calcineurin inhibitor, CNI; mycophenolate mofetil, MMF; and steroid). Recently, some authors reported successful outcomes of ABOi-KT without RIT and splenectomy.
Current strategies of ABOi-KT compose three common principles:
(1) antibody measurement. (2) B-Cell depletion. (3) antibody depletion .
ACCOMMODATION
Without adequate anti-A/B antibody reduction and desensitization before KT, an incidence of AMR and irreversible damage cannot be avoided. Successful ABOi-KT requires the reduction of anti-A/B antibody titers against ABO antigens on the graft at the time of KT. However, anti-A/B antibody titer returns to the baseline level within almost 1 wk after KT even if optimal desensitization is performed. Therefore, intense monitoring is necessary during critical first two weeks after ABOiKT. Accommodation is defined as a phenomenon whereby graft rejection is avoided despite reemergence of incompatible antibody.
CURRENT PROTOCOL OF ABOI-KT
In ABOi-KT, intensified immunosuppressive protocol usually starts before KT in order to deplete anti-A/B antibody. . RIT has been adopted in the place of splenectomy by majorities of centers. However, the timing and dose of RIT administrated remains variable. RIT or splenectomy-free protocols have successfully, used low dose IVIG after plasmapheresis. Postoperative IAs is not performed routinely and its use is determined by antibody titers. Maintenance immunosuppressive agents are mostly triple agents which are CNI, MMF and steroid. Tacrolimus is the CNI of choice in these ABOi-KT protocols. MMF was taken 7-14 d pretransplant in order to inhibit antibody production. Some centers use a protocol without daclizumab, basiliximab or antithymocyte globulin, and report excellent outcomes. Thus it is controversial whether these clonal antibodies should be introduced in ABOi-KT or not.
ADVERSE EFFECT OF ABOI-KT
Infection
Malignancy
COST OF ABOI-KT
It is recognized that KT is a cost-effective option over dialysis
saja Mohammed
3 years ago
ABO incompatible renal transplants: Good or bad?
previously ABOI kidney transplant was contraindication due to the risk of hyper acute rejection, the experience with ABOI KTX comes from Japan when they use ABOi KTX program in LD earlier when there is no access to DD program ,and they confirmed its effectiveness with comparable graft survival to ABOc KTX by many observational studies with modification of desensitization protocols over time and better understanding of immunology nowadays ABOI- transplantation practiced in many centers in US and Europe with very acceptable outcome .So ABOI-KT is good, helped in reduce the waiting list and time with expanding the pool of donor access in LD program, and associated with better patient’s prognosis compared to waiting on dialysis and have similar graft survival to ABOc KT, also ABOI KT is cost effective.
Desensitization protocols for ABOI kidney transplantation evolving over time, yet not standardized, each center have their own protocol based on their experience, facilities, resources and infrastructure .
PLasmaphersis , DFPP,IA:
By principle the concept of desensitization based on antibodies removal by plasmapheresis (plasma exchanges, non-specific associated with removal of abs , antiviral ,antibacterial Igs and clotting factors with increased rate of infection, coagulopathy , bleeding tendency the use of immunoadsorption (IA) which is more selective and specific , preferred for HLA I , ABOI transplant with specific removal of anti-A,anti B abs with average reduction rate by 3-4 fold and associated with less infectious or bleeding side effects compared to plasma-exchange but more cost Immunomodulating agent IVIG:
have pleotropic effects including complement inhibition , FC receptors binding, inhibit B and T cells proliferation, CD8 T cell inhibition, with B cells apoptosis
No standardized dose, high dose, low dose usually given after plasmapheresis many side effects including infusion related allergic reaction, risk of thromboembolic events, AKI, its use in combination with plasmapheresis the preferred and widely used protocol with or without Rituximab. B cell depletion:
B cell depletion earlier protocols including surgical splenectomy which have been replaced by B cell depleting agent anti-CD 20 monoclonal AB, rituximab with different doses and frequency based on local center protocols but trend nowadays to use low dose rituximab usually 10 days pre operative again its part of intense immunosuppressive therapy associated with higher risk of infection like CMV, BKV, PJP.
Triple intense immunosuppression:
standard triple therapy in ABOI KTX have been moved over time from cyclosporine based to tacrolimus based with full dose MMF and prednisolone, pre transplant 2-4 weeks and continue as maintenance triple IS after transplantation , some centres tried early steriod withdraw after 1week with 100% graft survival .
Antibodies measurements:
Measurement of anti-A/anti B titers before and after ABOi transplantation is very important by Using different methods with no standardization among laboratories but flowcytometry is the more preferred and more accurate method but its use limited by cost and availability compared to tube technique, gel technique , The higher antibodies titer and the rapid rebound in first two weeks associated with higher rate of AMR and graft loss so its mandatory to continue post-transplant frequent monitoring for antibodies formation in first two weeks .
C4D staining positive in ABOI alone its common finding and indicate graft accommodation , for the diagnosis of AMR post ABOI KTX we need the combination of confirmed graft injury , C4D staining and ABS detection.
Mohamed Saad
3 years ago
ABO incompatible renal transplants: Good or bad?
Generally its good but nothing good 100% so it has also some pitfalls so it should be considered in special circumstances, therefore any recipient with an incompatible living donor should choose from three options.
(1) stay on the waiting list for deceased donor KT.
(2) have paired kidney donor exchange (PKDE).
(3) undergo ABOiKT
ABOiKT is a viable alternative to waiting on deceased donor list.
There are some merits and demerits for ABOiKT.
ABOiKT kidney transplantation has merits like:
-Saving many chances for kidney recipients .
-Increase the donor pool and so decreasing the donor waiting list.
-The outcome of graft survival in ABOiKT has been similar to ABOc-KT.
-Medical splenectomy (Rituximab) replaced surgical splenectomy.
(splenectomy-free protocols).
-ABOiKT become in progress currently because the protocols become more simplified and clear than before and due to its good graft and patient survival outcome.
ABOi kidney transplantation has demerits like:
-Challenges facing incompatible ABO transplantation and require new strategies.
-Heavily immunosuppressive protocol and desensitization, there are high risk of infection and malignancy.
– ABOi-KT had a significantly higher incidence of AMR compared to ABOc-KT without difference in ACR.
-Serial follow up of Isoagglutinin pre and post transplantation.
-Costly desensitization protocol specially for developing countries.
Manal Malik
3 years ago
ABO incompatible renal transplants:good or bad ?ABOi is good for these reasons:
1- lead to an expand donor pool and reduced the number of patients with ESRD awating deceased kidney transplant.
2- improved graft and patients survival compared whom spend waiting time long in dialysis and even with ABO c-KT.
3- KPDE for HLA (sensitize and or ABOi so create more compatible pairs so KPDE is low immunological risk ,avoid intensified immunosupression and cost effects.
4-Over come the shortage of deceased donor in some countries such as japan,
5-using Rituxmab in desensitization protocol useful for both AMR and CAMR prevention so observed that ABOi -KT with RITUXMAB has stasticly significant lower rate of CAMR at 2 year post transplant than ABOc-KT (3.5% versus 28.9%) .
6- accommodation phenomena so minimize the risk of immunosupression and in ABOi -KT here it remain speculative.
7- although in presence of heavy immunosupression medication the risk of malignancy same as ABOc-KT . ABOi -KT is bad as for :
1- intensified immunosuppression
using plasmapharasis with risk of all complication such as infection ,bleeding,hypocalecimia and hypo tension.
2- higher incidence of infection such as viral infection(CMV,EBV).
3- higher incidence of AMR due to anti A/B antibodies but no difference in acute cellular rejection compared with ABOc-KT.
4- increasing expenditure.
5-Antibody depletion therapy
6- using IVIG with all complication and other hand absence of control data ,the use of IVIG in ABOi-KT can best described as empirical.
7-absence of randomized trials to satisfy about different protocol.
8- ABOi-KT had sever transplant glommulapathy than ABOc -KT without HLA Ab at 1 year post transplant.
9- can not be implement in poor countries more expensive than ABOc-KT.
10- desensitization is require special centre with full filled criteria and need lab to monitor anti A/B antibodies titre so usually not available in all center as equipment is expensive
Heba Wagdy
3 years ago
Good
Graft survival is similar to ABO compatible transplant,
Increase number of potential living donors
Reduce waiting time on dialysis
Provide better quality of life than dialysis
More cost effective than dialysis on the long-term Bad
It is associated with higher immunological risk
It requires close monitoring of anti-ABO antibody titer before and after kidney transplant to detect any rebound in antibody production.
Increased risk of AMR
Several complication associated with treatments used for antibody depletion as plasmapheresis increase risk of bleeding and infection.
Immunoadsorption may be needed to reach acceptable titer but with high cost and is not available in all centers.
Needs intensified immunosuppression protocols
No available randomized controlled trials studying different immunosuppressive agents or the long term outcomes
Increased risk of post transplant infection.
It is a good chance for patients who can’t find a compatible donor nor participate in kidney paired donation, also it is better than remaining on dialysis. However, it is difficult to be applied due to the increased cost and higher immunological risk.
Last edited 3 years ago by Heba Wagdy
Zahid Nabi
3 years ago
I think it’s very good option for our country which doesn’t have a deceased donor programe or even PKD. It will definitely will increase the donor pool and many patients who otherwise will remain on dialysis will get a transplant.
The quality of dialysis in many third world countries including mine is not good so one should be very careful in interpreting dialysis survival data for such patients (as most of data is western or American etc). So We have to decide is it better to keep someone on poor quality dialysis or go for ABOi transplant?
Sahar elkharraz
3 years ago
It’s good because less waiting time and list
Improve quality of life rather than stay for long time on dialysis or dying while waiting for deceased donor
it’s give chance for paired kidney donor exchange with low immunological risk and benefit to get compatible donor
Good graft survival in comparison to ABO compatible
it’s Bad because high immunological risk
it’s very expensive for monitoring anti A/B antibodies titer and invasive method for removing antibodies by plasma exchange or immunoadsorption for removal B and T cell and risk to protocol of renal biopsy every 3 months
Risk to hazard of intensive immunosuppressive drug
High incidence of infection and malignancy
High risk of rejection
Sherif Yusuf
3 years ago
GOOD
Superior survival benefit when compared to maintaining patients on dialysis
Can reduce wating time in deseased donor transplantation
Allow for the increase in the living kidney donation pool including KPD
Accommodation of the graft can occur after the first 2 weeks of transplantation due to change in the nature and affinity of antibodies with subsequent increase in antibodies but with no associated ABMR
No increase in the risk of malignancy in ABOi transplantation
Bad
Danger of intensive immunosuppression including the increase in the risk of infection such as PSC, CMV, BK virus, which may be attributed to the use of rituximab
ABO I transplantation is expensive, it is estimated that the cost of ABOi transplantation over 20 years is 15% lower than dialysis, thus it is considered cost effective when compared to dialysis
Dangers and side effects related to stratigies used for desensitization such as plasmapharesis, IVIG, Rituximab
Significant increase in the risk of ABMR but not acute CMR
Little experience aquired in ABO incompatible when compared to HLA incompatible transplantation, prevalance of ABO incompatible transplantation is variable ranging from 1% in UK to 30 % of living kidney transplantation in Japan
Thank you What is your personal opinion, good or bad? Will you support this programme or you implement it under certain conditions?
Last edited 3 years ago by Professor Ahmed Halawa
Ibrahim Omar
3 years ago
Is it good or bad and why?
there is no a single answer for this question.
ABO incompatible kidney transplantation (ABOi-KT) is a form of a serious therapy for a serious disease. no doubt that any effective therapy should have serious side effects as long as beneficial therapeutic effects.
ABOi-KT was previously considered as an absolute contraindication for ESRD patients due to the possible hyperacute rejection.
ABOi-KT was 1st done 50 years ago. since that time, it is increasingly performed allover the world.
Why good ?
it expands the donor pool as more grafts are available for ESRD patients.
it decreases the number of ESRD patients awaiting deceased kidney transplants.
in recent years, the outcome is comparable to compatible transplants.
with the current protocols of desensitization, early graft loss and antibody mediated rejection (AMR) have been completely abolished.
despite being expensive, it is still cost-effective as compared to patients maintained on hemodialysis.
it involves a better quality of life as compared to hemodialysis.
Why bad ?
it is an expensive therapy due to the extra costs of desensitization protocols.
there is still residual immunological risks that can do allograft damage.
there is an increased risk of malginant disorders and serious infections due to the the intensive immunosuppression.
the antibody titre returns to the baseline level within 1 week after kidney transplantation, even with optimal desensitization. this requires intensive monitoring within the 1st 2 weeks.
it is a good procedure as it has been proved to be successful in many cases.
I will support this porgram because the risk/benefit ratio is in favour of doing it. then more benign and different desensitiztion protocols are expected to be developed in the near future. this new protocols will be less toxic and also effective. therefore, the risks will be significantly minimized.
Riham Marzouk
3 years ago
it is good and reasonable option for transplantation:
1- it is better to wait for NDD or DCD
2- in spite of high cost of desensitization protocol, it is less cost than the cost of staying on dialysis.
3-it allows to enlarge donor pool and allow more patient to leave dialysis and become transplanted so help to decrease cardiovascular mortality on dialysis.
4-same incidence of AMR between ABO incompatible and compatible donor transplantation
5- same risk of malignancy
6-desensitization protocol can be individualized to try to decrease cost
7-rituximab as a part of induction and also it replace surgical splenectomy
8- the concept of accommodation
BUT
1- we lack RCTs to judge well is it good or not
2-definite we face a problem of increase incidence of infection either bacterial or viral like CMV, BK…as a complication of heavy immunosuppression.
Thank you Riham for your reflection. You mentioned an important point that ABOi transplantation is cheaper than dialysis. Can you prove this point please for us and provide evidence.
COST OF ABOI-KT It is recognized that KT is a cost-effective option over dialysis[104-106]. The estimated cost for ABOi-KT over 20 years was $315600, which was approximately 15% lower than dialysis[107]. ABOi-KT is more expensive than ABOc-KT because of requirement for desensitization and removal of anti-A/B antibody. The cost of ABOi-KT in the first 90 d posttransplant is $90300 compared to $52500 for ABOc-KT[108]. The additional cost of ABOiKT amounts to €31948 for IAs, RIT, IVIG, and prolonged hospital stay[31]. The cost of single IA is approximately €4340-1433[40]. However, despite more expensive, ABOi-KT is still more cost-effective than dialysis in the long-term and delivers a better quality of life.
this is from same paper
but i mean that ABOI transplant on long term will be cost effective in comparison to the burden of dialysis and its cost and also the cost of its complication beside better quality of life post transplant in comparison to stay on dialysis
Ban Mezher
3 years ago
Although renal transplantation is the treatment of choice for patients with ESRD, but it had big obstacle which is the shortage of donor pools ( deceased & live). ABOi-KT can reduce the waiting time for those patients. It is a good option because :
comparing to patients kept on dialysis, the patient with ABOi-KT had better survival due to reduce waiting list time ( median waiting time depend on blood type ~4 years)
it offer good donor pool for countries not used deceased donor
Blood group A had 2 Ags ( A1, A2). Expression of A2 Ag is weak & it found only in 20% of white race, so A2 graft may be less likely to suffer from rejection, & transplantation can be done without preconditioning.
abandoned splenectomy as apart of desensitization regime & replaced by rituximab ( avoid complication of splenectomy).
Accommodation
minimization of immunosuppression, e.g. early withdrawal of steroid in ABOi KT had good graft & patient survival
similar graft survival of ABOi-KT & ABOc-KT inspire of increased AMR rate among patients with ABOi-KT
cost effective when compared to dialysis
risk of malignancy not increased when compared to ABOc-KT.
Thank you, Ban for your answer. You mentioned an important point that ABOi transplantation is cheaper than dialysis. Can you prove this point please for us and provide evidence.
Estimated cost of ABOi-T over 20 years ~$315600 which is 15%lower than cost of dialysis & ABOi-T provide better quality of life.
Doaa Elwasly
3 years ago
The good side of ABOi KT is that it expanded donor pool and reduced the number of recipents awaiting deceased kidney transplantation ie decreasing waiting time list.
The outcome of ABOi-KT has been comparable to ABOc-KT in adult and pediatric recipients.
ABOi cases can be enrolled into Paired kidney donation exchange PKDE programs either through three-way, four-way and domino paired donation which has advantages having less immunological risk, needs less immunosuppression, and is cost effective if compared with dialysis and also provides better quality of life.
For blood group A ;A2 kidney is less susceptible to have antibody rejection in the presence of anti-A antibody. Non-A recipients receiving kidneys from A2 donors can safely accept the transplantation because A2 antigen expression is weaker than A1.
ABOi-KT preoperative management includes:
(1) antibody measurement mainly through flowcytometry ,tube and gel technique.
High preoperative anti-A/B IgG titers correlates with poor long-term allograft survival in ABOi-KT
(2) B-Cell depletion by splenectomy because it decreases the risk of antibody mediated rejection but this was not confirmed because rejection occurred after splenectomy, currently it is replaced by Rituximab, Rituximab is used in AMR, and in chronic antibody-mediated rejection (CAMR) prevention.
(3) antibody depletion by plasma exchange,DFPP, immunoadsorpant,the latest is more effective with less side effects but is more expensive and IVIG is usually used after plasmapheresis to avoid AMR
Accommodation is a mechanism where graft rejection doesnot occur inspite of reappearnance of incompatible antibodies.
The Eurotransplant protocol is IAs followed by high dose of IVIG then triple immunosupreesion with Tac ,MMF ,and steroids.
The bad side of ABOi-KT, is seen in the superadded immunological risk that can cause allograft damage, inspite of intensified immunosuppressive protocols increasing risk of infection and malignancy.
Also desensitisation increased the expenses of the transplantation
As in splenectomy a B cell depletion method , patient is susceptible for life threatening sepsis and infection with encapsulated organisms and he will need lifelong prophylaxis as well as it’s surgical complications ,currently splenectomy free protocols are used
ABOi-KT had more severe TG than ABOc-KT without HLA antibody at 1 year posttransplant
ABOi-KT had a significantly higher incidence of AMR compared to ABOc-KT on the other hand ,some studies showed no difference .
The rates of infection including mostly BK virus (BKV), cytomegalovirus (CMV), herpes simplex virus, and varicella zoster virus in ABOiKT were significantly higher than in ABOc-KT
Some studies mentioned that ABOiKT is not associated with an increased incidence of malignancy after KT but long term studies for ABOiKT after rituximab treatment is needed
Yes I support this program it’s advantages outweigh it’s disadvantages
Radwa Ellisy
3 years ago
– I think it’s a good option if failed paired kidney donation or if it is unavailable
– It is better compared with waiting for a deceased donor or being on dialysis for a long time
– Why?
It carries graft survival equivalent to ABOc-KT, but with higher ABMR rate and similar TCMR
It expands donor pool and decreases waiting loss
Provide better prognosis for patients rather than being on dialysis
But
Require monitoring of level abs pre and post tx (better with flowcytometry)
Intensive immunosuppression including IVIG, rituximab, and triple IS(CNI, MMF, and prednisolone) as maintenance
– Careful monitoring and suspicion for viral infection especially BK virus
Very impressed Radwa. You put your own reflection very clear. Your summary is very short and up to the point. I agree with every single word you mentioned.
Good
Leads to increase in donor pool
decrease in donor waiting list time .
outcome of ABOi-KT has become equivalent to ABOc-KT in adult and pediatric recipients.
Improvement of patients prognosis
Better quality of life for the patient.
live donor ABOi-KT is a viable alternative to waiting on
deceased donor list.
Bad
Higher incidence of AMR (17.9%)
Comparative high immunological risk.( acceptable titre of antibody pre transplant not clearly defined and also the protocol is not standardised)
Intensified immusuppresion , pre transplant rituximab, plasmapharesis/DFPP/IAs with post IvIg needed.
Increased cost of transplant initially ( additional cost for IAs, RIT, IVIG is 31948 pounds, however more cost effective than dialysis in the long term( 15% lower cost as compared to remaining on dialysis for 20 years.)
Higher incidence of viral infections like CMV,HSV, Varicella zoster and BK virus which is most common(25%).
# Advantage of ABOi-KT
Reduce the waiting list and time
Expanding living donor pool
Improvement of patient’s prognosis
Excellent graft survival (comparable with ABOc-KT)
A2 blood group may be less likely to suffer antibody rejection in the presence of anti-A antibody. In fact, non-A recipients receiving kidneys from A2 donors, can universally and safely accept the transplantation without preconditioning at times of KT
Plasmapheresis (PP)and splenectomy were performed to reduce (anti-A/B) antibody and to minimize the risk of hyper acute humoral rejection. Splenectomy has been totally abandoned and the various desensitization protocols in use are combinations of antibody removal by (PP) or (IA), (IVIG) to neutralize preformed antibodies, B lymphocyte depletion by anti-CD20 monoclonal antibody (RIT) and standard triple immunosuppression (CNI; MMF; and steroid). Recently, they reported successful outcomes of ABOi-KT without RIT and splenectomy.
ACCOMMODATION
Without adequate anti-A/B antibody reduction and desensitization before KT, an incidence of AMR and irreversible damage cannot be avoided. Successful ABOi-KT requires the reduction of anti-A/B antibody titers against ABO antigens on the graft at the time of KT. However, anti-A/B antibody titer returns to the baseline level within almost 1 wk after KTeven if optimal desensitization is performed.
# Disadvantage of ABOi-KT
Comparative high immunological risk
Higher incidence of acute AMR
Intensified immunosuppression
Antibody depletion therapy
Increasing expenditure
Higher incidence of infection, the infection rate in ABOi-KT is significantly higher than in ABOc-KT (60% vs 29.8%).
Malignancy It is generally accepted that immunosuppression is associated with an increased incidence of malignancy in KT recipients compared to the general population. However, several studies have demonstrated that ABOi-KT did not
increase the risk of posttransplant malignancy compared with ABOc-KT.
ABOi kidney transplantation is favorable for the followings:
· ABOi-KT has led to an expanded donor pool and reduced the number of patients with ESKD awaiting deceased kidney transplantation (KT) .
· ABOi-KT outcome is comparable to ABO compatible KT (ABOc-KT).
· There has been an evolution in ABOi- KT leading to a simplification of protocols over the last decade and this may help reducing the cost of desensitization and pre-transplant treatment.
· Accommodation phenomenon has been noted in ABOi transplantation, whereby graft rejection is avoided despite reemergence of incompatible antibody.
ABOi transplantation; the demerits
· The cost of pre-transplant management.
· The risk of infection associated with desensitization and intensive immunosuppression.
· The risk of early hemorrhage.
Is it good or bad ? why
It has some advantages and some disadvantages
Advantages
If the patient with ESKD has an ABO incompatible living donor, the patient can chose one of three options: (1) stay on the waiting list for deceased donor KT; (2) have paired kidney donor exchange (PKDE); or (3) undergo ABOi- KT.
The outcome of graft survival inABOi-KT has been similar to ABOc-KT.
Disadvantages
There is an increased risk of AMR in ABOi-KT due to anti-A/ B antibody. Protocol biopsies at 3 mo posttransplant in ABOi-KT had a significantly higher incidence of AMR
compared to ABOc-KT. However, there was no significant difference in the rate of acute cellu- lar rejection between ABOi-KT and ABOc-KT
PE removes not only anti-A/B antibody, but also coagulation factors and anti-viral/-bacterial immunoglobulin. Consequently, the risk of bleeding and infection is increased.
Significant amounts of albumin are lost by DFPP, and almost always albumin is needed as the replacement fluid. DFPP is also removes variable amount of fibrinogen.
ABOi-KT is more expensive than ABOc-KT because of requirement for desensitization andremoval of anti-A/B antibody.However, despite more expensive, ABOi-KT is still more cost-effective than dialysis in the long-term and has a better quality of life.
The infection rate in ABOi-KT is significantly higher than in ABOc-KT (60% vs 29.8%) . The rates of in fection including cytomegalovirus (CMV), herpes simplex virus, varicella zoster virus and BK virus (BKV)
Blood group compatibility was once considered a necessity for renal transplant. Now a days ABO incompatible transplant as equal rates of success as compared to normal blood group transplant. It started with Japan and then worldwide different protocols are present to make this transplant a success.
Advantages:
The patients get transplanted faster rather than remaining on the waitlist. The Living donor pool is also increased by this technique and more live transplants can be encouraged. ABOi transplants increase the likelihood of transplants by 30%. The patients definitely show a survival advantage as compared to waiting on dialysis.
Disadvantages:
Patients need more immunosuppression for anti A/B titre removal. There is more incidence of viral infections like CMV/EBV. There is more incidence of AMR as compared to ABOc transplants (17.1% vs 1.5%).However the rates of TCMR are similar.. Patients are predisposed to more sepsis episodes as plasmapheresis removes normal immunoglobulins also. The studies do not show an increased incidence of PTLD, but further data is needed..
In conclusion, if no suitable blood group compatible donor is available, it is best to to convince the family for an ABOi renal transplant given the improved survival rates and less toxic desensitization protocols especially if the Anti A/B titre <1:512 and Blood group A2.
Actually, it is not the matter of good or not. Every treatment has certain risks but the decision is based on the need of this treatment. since Kx is the best modality of RRT for patients with ESRD so waiting for ABOc tx will increase the waiting list. The studies showed ABOi tx with good selection of the donor and good desensitization protocol with post kidney transplant good follow up protocol along with good Is regimen is better than remaining on dialysis waiting for ABOi. Hence, with above mentioned good protocol, still there is risk of ABOi including AMR, infection, high risk of bleeding.
The advantages of ABO incompatible transplants include:
-Increasing the number of the available donors which is still better than remaining on dialysis .
The disadvantages of ABO incompatible transplants include :
-These transplants have a higher level of immunological risks than ABO compatible transplants.
But still this is a better option under certain circumstances than waiting for a deceased donor kidney or a better matching living donor .
ABOi KT is a good option for high risk patient rather to keep the patient on Dialysis
advantages :
Reducing waiting list and time.
Expanding living donor pool .
Improvement of patient’s prognosis.
Disadvantages of ABOi-KT :
it is considered high immunological risk.
More costly
Higher incidence of acute AMR .
Intensified immunosuppression .
Higher incidence of infection.
it is good because:
1- It increases the living donor pool
2- Reduces the number of patients on the waiting list and reduces the waiting time to receive kidney transplantation.
3- Improve the prognosis of the patients
4- It has comparable graft survival with ABOc-rTx
It is bad because of:
1- It carries high immunological risk
2- Has a higher incidence of acute AMR.
3- More cost
4- Powerful immunosuppression use
5- Pharesis treatment that requires trained staff and more expenditure with more adverse effects
6- Higher incidence of infection and malignancy
7- No universal protocol yet for pre-transplant desensitization.
8- No universal accepted cut point for isoagglutinin titer.
9- Different techniques for isoagglutinin assay.
10- C4d staining can not be used as a marker for ABMR.
General overview for ABO incompatible renal transplants.
The advancement of intensified immunosuppressive protocol has increased successful ABO incompatible kidney transplantation (ABOi-KT) in the recent years. However, there are few concerns regarding residual immunological risks which might lead to allograft damage. This article focus on the transitional outcomes alongside current and future prospects in ABOi-KT.
Pre transplant management consist of antibody measurement by using either tube technique, gel technique and flow cytometry , B-Cell depletion and antibody depletion.
Assessment of anti-A/B antibody titer is essential in ABOi-KT by assessing pre-operative severity of ABO incompatibility and thus decide on optimal duration for transplantation to proceed. Besides, antibody rebound post-transplant is an early sign for antibody-mediated rejection (AMR). High pre-operative anti-A/B IgG titers is a good predictor for AMR. Post-transplant rapid increase of anti A and anti B titers is also associated with AMR and graft loss. The acceptable antibody tires ranging between 1:4 and 1:32.
B cell depletion can be achieved either by splenectomy or Rituximab. Although the efficacy of splenectomy in ABOi-KT is debatable but it could be useful as salvage treatment for severe AMR secondary to anti-HLA antibody. On the other hand, Rituximab which is anti-CD20 monoclonal antibody cause depletion of B cell. The indications of Rituximab include ABO- and HLA-incompatible KT, treatment of AMR and post-transplant lymphoproliferative disorder. However, we should caution and monitor closely for side effects of Rituximab.
Antibody depletion include plasma exchange (PE), doublefiltration plasmapheresis ( DFPP ) and Antigen-specific immunoadsorption ( IA ) . However, PE increase risks of infection and bleeding due to non selective apharesis. On the other hands, DFPP remove selectively the immunoglobulin from plasma and requires less substitution fluid compared to PE. IA can be A/B antigen IAs or A/B non-antigen IAns (non-specific/semi-selective immunoadsorption) respectively if it removes only a specific antibody such as anti-A/B antibody or removes non-antigen-specific immunoglobulin. IAs is most utilized method in HLA incompatible/ABOi KT recipients. Hence, IAs is generally regard as the most effective and safe compare to other methods of antibody depletion.
In ABOi-KT, the indication of IVIG is recommended for recipients with low anti-A/B titer in order to avoid hemolysis and AMR after transplantation.
Current intensified immunosuppressive protocol include the usage of Rituximab without splenectomy following plasmapharesis with low dose of IV IG. Maintenance immunosuppressants are mostly triple agents which are CNI, MMF and steroid. However, choices of immunosuppressants need to be individualized by weighing risk of rejection and long term risks of oversuppressions.
Increase anti-A/B antibody titres is one of the sign of early graft loss. Acute AMR is evidence by C4d staining in the peritubular capillary (PTC) and the presence of anti-donor antibodies. However, C4d deposition without AMR was seen in 85.7% of ABOi-KT at 3 mo post-transplant. Morphologically transplant glomerulopathy (TG) at 1 year after transplantation was reported as an indicator of poor outcome and graft survival. ABO incompatible grafts had a high incidence of AMR compared to ABO compatible grafts (27% vs 5.3%).However, the rejection rates in ABOi-KT were similar to that in ABOc-KT.
The points favour for ABOi-KT include reducing waiting list and time, expanding living donor pool, Improvement of patient’s prognosis and excellent graft survival (comparable with ABOc-KT). On the other hands, the disadvantages of ABOi-KT include comparative high immunological risk, higher incidence of acute AMR, side effects of over intensified immunosuppression therapy, increase medical expenditure and risks of infections.
In conclusion, ABOiKT is more costly than ABOc-KT which may restrict its application in centre with poor resources. In centre whereby ABOiKT is possible, we need to personalized the preparation and follow up plan for ABOiKT recipients. The include preconditioning treatments and maintenance immunosuppressants. With good medical resources ABOiKT provide good outcome for end stage renal failure patient. However, early recognition of AMR and prompt treatment is crucial for graft survival.
ABOi – KT expanded the donor pool and can be performed by using desensitization protocols and its outcome is comparable with ABOc-KT in recent years.
But there is still risk of allograft damage or increased rate of infection or malignancies. Other choices are: Stay on waiting list for deceased donor KT, paired kidney donation or ABOi-KT. Presence of anti-A or anti-B Abs is an obstacle for TX of a different BG. A2 Ag is weaker and is the subtype for 20 % of cases. A2 kidney can be safely transplanted to a non -A recipient. To perform ABOi-KT, there common principles are:
(1) Ab measurement: acceptable titer at the time of TX varies between 1:4 and 1:32
(2) B cell depletion: Rituximab has replaced splenectomy in ABOi – KT which Binds to CD20 and causes B cell depletion.
(3) Ab depletion by DFPP, IA or PE.
IVIG is usually administered after PE.
· Accommodation:
After one week after ABOi-KT, Anti-A / B Abs returns to baseline.
Accommodation is a phenomenon in which AR is avoided despite incompatible Abs. Presence of C4d alone in ABOi-KT is not an indicator for AMR. TG after first year shows poor outcome.
There is a significant increase in acute rejection in ABOi-KT and there is need for protocol biopsies. The infection rate in ABOi-KT is significantly higher. CMR, HSV, VZV and BKV rates were higher in ABOi-KT.
ABOi-KT is a cost-effective option than dialysis but more expensive than ABOc-KT. So, different conditions of patients or TX centers are effective regarding this kind of Treatment.
Its good option for high risk patient.
ABOi-KT is still more cost-effective than dialysis in the long-term and delivers a better quality of life.
advantage:
Pro ABOi-KT :
Reducing waiting list and time.
Expanding living donor pool .
Improvement of patient’s prognosis.
Excellent graft survival (comparable with ABOc-KT)
Contra ABOi-KT :
Comparative high immunological risk.
Higher incidence of acute AMR .
Intensified immunosuppression .
Antibody depletion therapy.
Increasing expenditure.
Higher incidence of viral infection.
Undoubtedly, it is an excellent way to include several patients who are waiting for a more compatible deceased donor. The American program itself describes the possibility of transplanting a third of the waiting list that was previously expected for compatibility. Blood type O, historically considered to have the worst prognosis for having both A and B antibodies, increases your opportunity for more compatible live donors.
ABOi Renat transplantation is good as the last chance for patients in whom the transplantation is better than remaining on dialysis. It is not practised in many countries because of being expensive. the advantage is the reduction of waiting time affecting health status and decreasing the mortality related to dialysis itself and sensitization etc.
ABOI -KT has advantages of shortening waiting time by increasing of living donors offers, better QOL and outcome compared with HD. and graft survival may be comparable to ABO C-KT on long term. However, disadvantages include risk of rebound post transplantation even with desensitization which could end by AMR and graft loss ,and complications and cost of use of aggressive immune-suppression during desensitization and treatment of acute rejection episodes.
So ,ABOI-KT can be useful if the patient does not find ABO C donor with long waiting time. It requires expertise and maneuvers of desensitization and after agreement of recipients regarding aggressive medications and its complications .
ABO-incompatible renal transplants: Good or bad?
it’s a good option for ESRD patients on dialysis but not the best option in comparison to ABO compatible kidney transplantation
why??
-regarding graft survival and patient survival there is a statistically nonsignificant difference between ABO compatible and non-compatible but associated with increased risk of infection, ABMR, the patient is exposed to more intense immunosuppression and more expensive
1 Expanding the donor pool, especially for recipients on the long waiting list
2- better survival outcome in comparison to staying on dialysis (better prognosis)
3- a flexible chance for transplantation after the introduction of new protocols for reduction of A/B antibodies with a better outcome, minimizing the risk of ABMR
4-decrease time of waiting list of recipients
5-excellent graft outcome in comparison to ABOc-KT
1-high immunological risk
2-higher incidence of ABMR
3-need more Immunosuppression with more risk of infection added
4-increase cost for pre-transplant preparation for reduction of ABO antibodies titer with target less than 1/32
5-higher incidence of infection especially BKV and Pneumocystis jiroveci
6-long period for close follow up for early detection of ABMR
So I think it’s good to go for ABOi-KT instead of keeping your patients on dialysis for better survival and quality of life despite our transplantation committee doesn’t allow till now for ABOi-KT also in developing countries it may be more financial burden due to the high cost of immunosuppression used in the reduction of anti A/B antibodies titers
Its good, because has led to an expanded donor pool and reduced the number of patients with end-stage kidney disease awaiting kidney transplantation. Despite, there is the increased the risk of hyperacute rejection, the ABO incompatible renal transplante outcome of graft survival is comparable to ABO compatible with the use current desensitization protocols. The increasing risk of infection and possibly malignancy its other problem, but the cost is the biggest constraint.
Advantages
Expanded donor pool.
Reduced the number of patients with ESKD awaiting deceased kidney transplantation.
Accommodation phenomenon whereby graft rejection is avoided despite reemergence of incompatible antibody (possibly due to changes of antibody specificity, avidity, affinity and alteration of the antigen structure).
The outcome of graft survival in ABOi-KT has been similar to ABOc-KT.
The incidences of rejection, graft survival rate and function of ABOi-KT patients were compatible with these of ABOc-KT patients.
ABOi-KT did not increase the risk of post-transplant malignancy compared with ABOc-KT.
The estimated cost for ABOi-KT which was approximately 15% lower than dialysis and delivers a better quality of life.
Disadvantages
Usually intensified immunosuppressive protocols at the expense of increasing risk of infection and possibly malignancy.
Desensitization and antibody reduction therapies have increased the cost of KT.
High anti-A/B IgG titers is a predictor for AMR.
Adverse events related to B-cell depletion by Rituximab include fever, chill, headache, and nausea.
Plasma exchange has several disadvantages compared with more specific techniques because of non-selective apheresis, PE removes not only anti-A/B antibody, but also coagulation factors and anti-viral/-bacterial immunoglobulin thus, the risk of bleeding and infection is increased. The most common complication was hypocalcaemia.
ABOi-KT had more severe transplant glomerulopathy than ABOc-KT without HLA antibody at 1 year post transplant which is an indicator of poor outcome.
The infection rate in ABOi-KT is significantly higher than in ABOc-KT (60% vs 29.8%). The rates of infection including cytomegalovirus (CMV), herpes simplex virus, varicella zoster virus and BK virus (BKV) in ABOi-KT were also significantly higher than in ABOc-KT. The most common viral infection was BKV in 25% of ABOi-KT compared to only 8.5% of ABOc-KT.
The occurrence of early graft loss and AMR are not completely abolished.
ABOi -KT was considered an absolute contraindication for transplantation due to risk of hyperacute rejection .
ABOi-KT is now performed increasingly all over the world which helped to increase the donor pool and reduced the awaiting time for deceased kidney transplantation (KT).
Advances in immunosuppression and desensitization protocols allowed successful ABOi-KT outcome
PKDE is an option which provides a recipient with an incompatible donor the chance to receive a compatible kidney, Advantages of PKDE are low immunological risk, avoidance of intensified immunosuppression due to desensitization, and cost effectiveness.
Although the use of ABOi-KT has increased worldwide, there are arguments against ABOi-KT as a universal treatment.
●it good or bad and why?
Advantages:
1 expand the donor pool.
2 decreases waiting time for transplantation which is associated with better outcomes as compared to patients on dialysis.
3 after advances in immunosuppression and desensitization protocols it became comparable to ABO Compatible transplantation with no difference in incidence of AMR or long-term graft survival.
4 the acceptable titer of anti-A/B antibody at the time of transplant has varied between 1:4 and 1:32 in the protocol of individual centers allowing more flexible protocol not strict to a very low titer.
Disadvantages:
1 High preoperative anti-A/B IgG titers are associated with poor long-term graft survival.
although Chung et al,described no statistically significant difference between high- (> 1:256) and lowtiter (< 1:128) at the baseline in allograft function at 6 mo after transplantation.
2 it is un clear how long the monitoring should be continued.
4 higher incidence of ABMR.
5 intensified immunosuppression with higher incidencef infection and malignancy.
6 higher cost.
7 it needs more experienced centres.
Despite these disadvantages ABOI KT is still better option than being on dialysis when no other available compatabile donor available
ABO incompatible renal transplants Good or bad?
Advantages;
1- Reducing waiting list and time;
Different ways have been proposed to increase the donor pool and ABO incompatible KT (ABOi-KT) represents a valid source of organs to decrease the donor waiting list.
2-Expanding living donor pool;
When a patient with ESKD requires KT and an acceptable living donor is ABO incompatible with the recipient, the patient can currently chose one of three options: (1) stay on the waiting list for deceased donor KT; (2) have paired kidney donor exchange (PKDE); or (3) undergo ABOi KT.
3-Improvement of patient’s prognosis
4-Excellent graft survival (comparable with ABOc-KT);
The outcome of graft survival in ABOi-KT has been found to be similar to ABOc-KT. In ABOi-KT, acute AMR by anti-A/B antibody is a well recognized cause of early graft loss.
Disadvantages;
1-Comparative high immunological risk;
Blood type incompatibility means the exposure of A or B antigen to a person who has antibodies against these antigens. Therefore, these antigen expressions of an organ have been obstacles for ABOi-KT . Blood group type A, however, carries A1 or A2. The expression of A2 antigen is weaker than that of A1 antigen . A2 kidney may be less likely to suffer antibody rejection in the presence of anti-A antibody. In fact, non-A recipients receiving kidneys from A2 donors , can universally and safely accept the transplantation without preconditioning at times of KT.
2-Higher incidence of acute AMR;
There is an increased risk of AMR in ABOi-KT due to anti-A/B antibody. Acute rejection in ABOi-KT was mainly AMR (73.3%) as compared to ABOc-KT without HLA antibody (12.5%). However, there was no significant difference in the rate of acute cellular rejection between ABOi-KT and ABOc-KT .
3-Intensified immunosuppression;
Is associated with increased risk of opportunistic infections . Efforts have have been made to minimize immunosuppression in order to reduce the long-term risk of over immunosuppression .
4-Antibody depletion therapy
Because of non-selective apheresis, PE re-moves not only anti-A/B antibody, but also coagulation factors and anti-viral/-bacterial immunoglobulin. Consequently, the risk of bleeding and infection is increased. he most common complication was hypocalcemia (6.8%), followed by urticaria or pruritus (4.3%), hypotension (2.9%) and nausea or vomiting (1.2%).
DFPP is designed to remove selectively the immunoglobulin from plasma and requires less substitution fluid compared to PE. Significant amounts of albumin are lost by DFPP, and almost always albumin is needed as the replacement fluid. DFPP is also removes variable amount of fibrinogen [, and its measurement is necessary to avoid bleeding complication.
IAs is selective and free from side effects of PE and DFPP. Single IAs reduces 2- to 4-fold titer between pre- and post-IAs, and at least four preoperative IAs are usually needed to obtain an acceptable titer at the expense of increased cost compared to PE and DFPP .
.
5-Increasing expenditure
6-Higher incidence of viral infection
The infection rate in ABOi-KT is significantly higher than in ABOc-KT .The most common viral infection was BKV in 25% of ABOi- KT compared to only 8.5% of ABOc-KT. However, ABOi-KT patients who were treated with RIT, may have had different infection profiles. Polyoma virus infection rate (64.3%) was relatively high in RIT. Moreover, infection related-death was significantly higher in RIT treated patients.
Malignancy ;
Several studies have demonstrated that ABOi-KT did not increase the risk of post transplant malignancy compared with ABOc-KT.
Cost of ABOi-KT;
It is recognized that KT is a cost-effective option over dialysis. ABOi-KT is more expensive than ABOc-KT because of requirement for desensitization and removal of anti-A/B antibody. The cost of ABOi-KT in the first 90 d posttransplant is $90300 compared to $52500 for ABOc-KT . However, despite more expensive, ABOi-KT is still more cost-effective than dialysis in the long-term and delivers a better quality of life.
ABO-incompatible kidney transplantation: Is it a good or a negative thing?
Advantages include: -a live donor ABOi-KT is a potential alternative to waiting for a kidney transplant or being placed on a dead donor list.
– ABOi-KT has resulted in an increase in the number of potential donors.
When ABOi-KT occurs, there is a phenomenon known as accommodation, which is defined as the prevention of graft rejection despite the reemergence of incompatible antibodies.
– The outcome of graft survival in ABOi-KT has been shown to be comparable to that of ABOc-KT.
In ABOi KT, there was no increase in the risk of malignancy.
As a result, the infection rates of ABOi-KT were considerably greater than the infection rates of ABOc-KT for cytomegalovirus (CMV), herpes simplex virus, varicella-zoster virus, and BK virus (BKV), among other pathogens.
– Anti-A/B antibodies are associated with an increased risk of AMR in ABOi-KT patients. There was no statistically significant difference in the rate of acute cellular rejection between ABOi-KT and ABOc-KT, on the other hand,
-Increase the likelihood of adverse effects associated with desensitization procedures.
Treatment is more expensive than ABOc-KT because of the need for desensitization and elimination of anti-A/B antibodies; nevertheless, even though it is more expensive in the short term, ABOi-KT is more cost-effective than dialysis in the long run and provides a higher quality of life.
my opinion: ABOi should be individually evaluated and also the availability of the resources in the transplant centre is very important.
Why ABO I -KT?
Why not?
In conclusion, it can be used only if the patient does not find ABO c donor after long waiting time.
It is only done in case of available expertise and maneuvers of desensitization and after acceptance of the idea of aggressive medications and possible complications by the recipients.
Although ABOi-KT is more expensive than AB- Oc-KT because of requirement for desensitization and removal of anti-A/B antibody, It is recognized that KT is a cost-effective option over dialysis.
despite lack of control trials in ABOi-KT, more than satisfactory outcomes have been observed in adult and pediatric recipients, in many studies equivalent to living ABOc-KT.
The advantages of ABOi-KT:
Reducing waiting list and time
Expanding living donor pool
Improvement of patient’s prognosis
Excellent graft survival (comparable with ABOc-KT)
Disadvantages ofABOi-KT:
Comparative high immunological risk Higher incidence of acute AMR
Intensified immunosuppression Antibody depletion therapy
Increasing expenditure
Higher incidence of viral infection
Advantages:
Disadvantages:
ABO incompatible renal transplants : Good or bad ?
ABO incompatible kidney transplantation(ABOi-KT) is a useful source of organs decreasing the donor waiting list after certain preoperative preparation.
If an ESRD has a donor who is ABO incompatible, there are three choices :
1- Stay on waiting list for deceased donor.
According to the Organ Procurement and Transplantation Network(OPTN) report 2011, 86500 patients on the deceased donor waiting list and almost 28000were added annually to the list in the united states. 10000 patients received deceased donor kidney transplantation and 4900received living KT.
5000 patients on dialysis died while waiting for a kidney. The median waiting time is around 4 years.
2- To have a paired kidney donor exchange(PKDE).
Here 2 or more incompatible couples of donor-recipient exchange donor to create 2 or more compatible pairs.
Started in 1980s where reported by Rapaport.
It increases donor source and decreases waiting list, has low immunological risk with avoidance of heavy immunosuppression and cost effectiveness.
3- Undergo ABOi-KT.
This first started in Japan due to the lack of deceased donors, accounted for approximately 30% of all living donor KT in Japan.
In United states only 738 cases (0.94%)were done between 1995 and 2010, the number is increasing annually.
In United Kingdom the number increased over the last decade from <10 per year to100 per year representing 1.0% of living donor transplant performance.
ABO Antigens and Antibodies:
Blood group O is a universal donor to all other groups.
Blood group B is a universal recipient to all other groups.
A: has A1 (dominant) and A2 antigens/ anti B antibody.
B: has B antigen / anti A antibody.
AB: has A and B antigens but no antibody.
O: has no antigens but has anti A and anti B antibodies.
ABOi-KT Preoperative Management:
1- Antibody measurement: to determine the degree of operative preconditioning and the time to permit transplantation.
For post-transplant monitoring for early detection of AMR by antibody rebound.
Measurement is by tube technique, gel technique and flow cytometry.
High preoperative anti A/B IgG titers is a predictor of AMR and associated with poor long term graft survival.
The accepted titer of anti-A/B antibody is between 1:4 and 1:32 in the protocol of different centers.
2- B-cell depletion:
Either by splenectomy with many disadvantages.
Or using Rituximab which is recently replacing splenectomy.
After a comparative analysis of splenectomized recipients compared to recipient treated with rituximab without splenectomy that showed no statistically significant difference in the anti-A/B antibody titer of KT and liver transplantation, a conclusion that splenectomy was not an essential pre-transplantation treatment in ABOi-KT.
3- Antibody depletion by:
a- Plasma Exchange(PE).
b- Double filtration plasmapheresis(DFPP).
c- Immunoadsorption (IA).
Use Of IVIG :
Its action is complement down regulation-interaction with Fc portion-inhibition of B/T cell proliferation- inhibition of CD8 T cell cytotoxicity- increased apoptosis of B cell.
Rare and serious side effects include renal toxicity, thromboembolic events, neurological, hematological, and dermatological toxicities.
IVIG preferable to be of low anti-A/B titer to avoid hemolysis and AMR.
Currant Protocol of ABOi-KT:
Splenectomy free protocols published in the last decade, it is replaced by Rituximab.
RIT or splenectomy free protocols have successfully used low dose IVIG after plasmapheresis.
North European protocol is IA followed by high dose IVIG
In Japan 2012 Uchida et al reported use of RIT of 150mg/m2 twice at -14 and 0 d, antibody depletion by DFPP or PE, no use of IVIG and the titer should be < 1:16.
Pre-transplant immunosuppression MMF/MPS at -1mo, CYA or TAC at -3d.
Maintenance immunosuppression CYA or TAC –MMF/MPS.
The Incidence of Acute cellular Rejection and Antibody Mediated Rejection in ABOi-KT:
Protocol biopsies at 3 month post-transplant in ABOi-KT had a significant higher incidence of AMR compared to ABOc-KT(17.9% versus 1.1% ) but no significant difference in ACR(48.4% versus 35.7%).
Gloor et al, Setoguchi et al, Wipler et al have reports on that.
The estimated cost for ABOi-KT over 20 years was 315600 Dolars which was 15% lower than dialysis.
So in conclusion
The advantages of ABOi-KT:
Reducing waiting list and time
Expanding living donor pool
Improvement of patient’s prognosis
Excellent graft survival (comparable with ABOc-KT)
Disadvantages of ABOi-KT:
Comparative high immunological risk
Higher incidence of acute AMR
Intensified immunosuppression
Antibody depletion therapy
Increasing expenditure
Higher incidence of viral infection
ABO incompatible renal transplants: Good or bad?
Advantanges :
-live donor ABOi-KT is a viable alternative to waiting on dialysis or
deceased donor list.
– ABOi-KT has led to an expanded donor pool.
-ABOi-KT is associated with accommodation which is defined as a phenomenon
whereby graft rejection is avoided despite the reemergence of incompatible antibodies.
– The outcome of graft survival in ABOi-KT has been similar to ABOc-KT.
-No increase in the risk of malignancy in ABOi KT.
Disadvantages:
-The rates of infection including cytomegalovirus (CMV), herpes simplex
virus, varicella-zoster virus, and BK virus (BKV) in ABOi- KT were significantly higher than in ABOc-KT.
– There is an increased risk of AMR in ABOi-KT due to anti-A/ B antibodies. However, there was no significant difference in the rate of acute cellular rejection between ABOi-KT and ABOc-KT.
-Increase side effects related to desensitization protocols.
– ABOi-KT is more expensive than ABOc- KT because of the requirement for desensitization and removal of anti-A/B antibodies but despite being more expensive,but ABOi-KT is still more cost-effective than dialysis in the long term and delivers a better quality of life.
Conclusion: I think ABOi-KT is better than waiting on deceased donor list or remaining on dialysis.
ABOi transplant is a mode of tx where bloodgroup barrier hasbeen crossed which was previously a contraindication, today is a possibilty which reduces waiting .
Whether it is good or bad, is definitely a difficult question to be answered.
GOOD-
1.decreases waiting time.
2.increases donor pool
3.decreases morbidity,mortality of hd,pd pts
4.better than deceased donor tx
5.comparable outcome according to ABOc
6.accomodation process is there
BAD-
1.bit of costly(desensitization)
2.more infections,malignancy(intesified
immunesuppression)
3.extra risk of rejection as ABOi.
So, three against and six in favour of ABOi, so mandate is good i think.
The verdict regarding ABO incompatible transplants, whether they are good or bad, depends on a number of ifs and buts.
Overall, ABO incompatible is a good thing to happen to the field of transplantation as it opens up transplant opportunities for patients who do not have a blood group compatible donor.
The advantages of ABO incompatible transplants include:
1) Expansion of the available donor pool with consequent increase in transplant rates and decreased waiting times.
2) The graft prognosis is equivalent to ABO compatible kidney transplants, although with increased AMR, is a big plus point, making it worth the risks involved.
3) Getting an ABO incompatible transplant is better than remaining on dialysis with respect to patient survival as well as cost-effectiveness.
The aspects of ABO incompatible transplants discouraging their use include:
1) There is no consensus on the ideal pre-operative isoagglutinin titres as well as a standard protocol to be followed (with a number of variations being used). This can create confusion especially if a new ABO incompatible program is being set-up.
2) These transplants have a higher level of immunological risks than ABO compatible transplants, and hence have higher rates of AMR especially in patients with high baseline titres or having rapid rebound of titres. It requires intensive monitoring both pre- and post-transplant.
3) Intensive immunosuppression used as well as the antibody depletion procedures used (plasmapheresis or immunoadsorption) increase the risk of complications including infections like CMV and BK virus (more with rituximab use), HSV, Varicella zoster virus, etc and increased risk of bleeding.
4) The cost of the transplant increases due to the desensitization procedures (Plasmapheresis, IVIG, anti-CD20 antibody etc) in comparison to ABO compatible transplants.
In a nutshell:
If a recipient does not have a blood group compatible donor, is not able to get a donor through kidney paired donor program, and has lower anti-blood group antibody titres (<1:128), only then ABO incompatible transplant should be offered. This is a better option than waiting for a deceased donor kidney, especially in our setup, where the waiting times are 5-6 years.
Dear Amit
I like your conclusion, it is excellent and up to the point “If a recipient does not have a blood group compatible donor, is not able to get a donor through kidney paired donor program and has lower anti-blood group antibody titres (<1:128), only then ABO incompatible transplant should be offered. This is a better option than waiting for a deceased donor kidney, especially in our setup, where the waiting times are 5-6 years”.
Thank you Professor.
ABO incompatible renal transplants: Good or bad?
ABOI kidney transplant was a contraindication due to the risk of hyper acute rejection,
Japan decided to do ABOi when there is no access to DD program and they showed comparable graft survival to ABOc KTX Now, ABOI- transplantation practiced in many centers in US and Europe with acceptable outcome.
Desensitization protocols for ABOI kidney transplantation has been evolving over time, no standardized protocol across the globe but it depends on center specific protocols
ABOi TX has been divided to Antibody measurement, B cell depletion and antibody removal
Antibodies measurements:
Measurement of anti-A/anti B titers before and after ABOi transplantation is better with gel method but flowcytometry is showed to be preferred and more accurate method but limited by cost and availability . The higher antibodies titer and the rapid rebound in first two weeks associated with higher rate of AMR and graft loss . post-transplant titer monitoring is important to prevent AAMR.
B cell depletion:
B cell depletion protocols including surgical splenectomy which have been replaced by B cell depleting agent anti-CD 20 monoclonal AB, rituximab . various doses have been tried but nowadays opt to use low dose rituximab usually 10 days pre-operative with higher risk of infection like CMV, BKV, PJP.
Antibody removal
Plasmapheresis, DFPP, IA:
Conventional PP has been used but with the risk of removing coagulants, Igs, calcium together with risk of allergic and hypotension. It requires large replacement fluid in the form of human albumin or FFP. DFPP more specific which remove specific Igs and requires less replacement fluid. IA reduce the 2 -4 fold of titer but cost will be expensive.
IVIG:
have pleotropic effects including complement inhibition , FC receptors binding, inhibit B and T cells proliferation, CD8 T cell inhibition, with B cells apoptosis
No standardized dose, high dose, low dose usually given after plasmapheresis many side effects including infusion related allergic reaction, risk of thromboembolic events, AKI, its use in combination with plasmapheresis the preferred and widely used protocol with or without Rituximab.
Triple intense immunosuppression:
standard triple therapy in ABOI KTX have been moved over time from cyclosporine based to tacrolimus based with full dose MMF and prednisolone, pre transplant 2-4 weeks.
GOOD:
1)it has reduced waiting list in patient No. and time
2) Expanding living donor pool
3) Improvement of patient’s prognosis as compared to Deceased donor transplantation
4) Excellent graft survival (comparable with ABOc-KT)
5) being cost effective as compared to remaining on dialysis as RRT
BAD:
1)carries a high immunological risk
2)Higher incidence of acute AMR
3)Intensified immunosuppression which renders the patient at higher risk of infections and theoretically at higher risk of malignancies
4) mandates Antibody depletion therapy which also has its own complications especially the widely available conventional plasma exchange.
5)Increasing expenditure
6)Higher incidence of viral infection, mainly polyoma BK virus infection in those treated with Rituximab
7) still there is no clearly defined desensitization protocol for ABOi K
Accommodation
Without adequate anti-A/B antibody reduction and desensitization before KT, an incidence of AMR and irreversible damage cannot be avoided. Successful ABOi-KT requires the reduction of anti-A/B antibody titers against ABO antigens on the graft at the time of KT. However, anti-A/B antibody titer returns to the baseline level within almost 1 wk after KT even if optimal desensitization is performed. Therefore, intense monitoring is necessary during critical first two weeks after ABOiKT. Accommodation is defined as a phenomenon whereby graft rejection is avoided despite reemergence of incompatible antibody
Overall, I would like to do ABOi KT as many as I can in my center as DDK is limited due to widely religious reasons. I find ABOi KT with improved protocols and preventatives measures to infections, will lead to success
Well done, thank you
Well done, thank you
ABO antigen and antibodies,
A,B and O antigens are polysacchccharide antigens which are found in the red cells , platelets and other tissues such as endothelium.
The Antibodies to blood group antigen are isohemagglutinins and can be either IgM or IgG.In kidney transplantation , its only IgG that is of significance.
Blood type A develop anti B anti bodies.Similarly blood type B develop anti A antibodies. While blood type AB has both A and B antigens , but no anti bodies, Blood group O has antibodies against B and A antigens and has no antigens.,
ABO incompatible patients represent a major hurdle for kidney transplantation as its associated with potential AMR. It was considered an absolute contraindication to kidney transplantation.
Blood group type A:
It carries A1 and A2.The expression of A2 antigen is weaker than A1 antigen.
A2 constitute approximately 20% of blood .
A2 kidney may be less likely to suffer antibody rejection in the presence of anti A antibodies.
Non A recipients receiving kidney from A2 donors, can universally and safely accept the transplantation without preconditioning at time of of KT.
Currently ABOi KT represent a valid source of organ to decrease the donor waiting list.
3 options are offered for ABOi :
1] KAS
2] PKD: advantages , are low immunologic risk, avoidance of intensified immunosuppression due to desensitization, and cost effectiveness.
3] ABOi KT: it has increased due to the fact that desensitization protocols has been simplified.
Current strategies of ABOi KT compose three common principles:
1] Antibody measurement:
A/B antibody titer is crucial in ABOi KT, as according to this titer effectiveness of preoperative conditioning will be assessed .similarly, post operative titer monitoring detect AMR by antibody rebound. The acceptable preoperative anti A/B level has fallen between 1/4 and 1/32.
2] B cells depletion;
Rituximab has replaced splenectomy as a strategy to deplete B cells. However , splenectomy is still often recommended in severe unresponsive cases of AMR.
3]Antibody depletion:
The antibodies depletion is the core of desensitization of ABOi transplantation. DFPP is commonly used, However ,IA has replaced PP with more efficient and less side effect , but highly expensive technique .
IVIG use:
mechanism of action:
1]complement down regulation.
2]interaction with Fc receptors.
3]Inhibit B/T cells proliferation.
4]Inhibit CD 8 T cell cytotoxicity
5]increase apoptosis of B cells.
Accommodation :
A phenomena whereby graft rejection is avoided despite reemergence of incompatible antibodies.
North Europe protocol ; IA followed by high dose IVIG, Post operative IA is not routinely performed ,but depend on Antibodies level. it was made to avoid over immune suppression and heightened risk of infection and malignancy
Maintenance immunosuppressants .
Triple agents involving CNI,MMF and Steroid.
Well done, thank you
ABOi Kidney Transplantation :
It is GOOD in that :
1)it has reduced waiting list in patient No. and time
2) Expanding living donor pool
3) Improvement of patient’s prognosis as compared to Deceased donor transplantation
4) Excellent graft survival (comparable with ABOc-KT)
5) being cost effective as compared to remaining on dialysis as RRT
On the other hand it is bad in :
1)carries a high immunological risk
2)Higher incidence of acute AMR
3)Intensified immunosuppression which renders the patient at higher risk of infections and theoratically at higher risk of malignancies
4) mandates Antibody depletion therapy which also has its own complications especially the widely available conventional plasma exchange .
5)Increasing expenditure
6)Higher incidence of viral infection , mainly polyomma BK virus infection in those treatted with Rituximab
7) still there is no clearly defined desessitization protocol for ABOi KT
Overall I think it is a good option when good preconditioning and later on follow up are feasible
Well done, thank you
Pros and Cons for ABO incompatible Kidney Transplantation
Pros ABOi-KT
Cons ABOi-KT
Thank you
Kidney transplantation is considered the best option for patients with the end-stage renal disease worldwide. Due to the shortage of translatable organs, another probable risky method was accepted for a kidney transplant, such as ABOi-KT, which expanded the donor pool & its outcome is comparable to ABOc-KT in both adults & pediatric recipients.
Although it increases the risk of infection & malignancy due to intensified
immunosuppressive protocol & increases the cost compared to ABOc-KT, it is
a good option for ABOi patients.
Alternatives to that is a waiting list for cadaveric donor KT, or paired kidney donor exchange.
ABOi-KT requires desensitization protocol, to avoid AMR , this can be done with the
current strategies:
1-antibody measurement (an excellent method is Flow cytometry ).
2- B-cell depletion ( nowadays with rituximab).
3-Antibody depletion.
Thank you
What is the difference in acute rejection rate between ABOi and ABOc transplantation?
I. ABO incompatible renal transplants: Good or bad?
Is it good or bad and why?
What makes ABO-I good?
– Shortage of donor pool necessitates the search for alternatives to PKD organs
– To reduce the number of ESRD on deceased donor waiting list & improve patients prognosis.
– Outcomes are comparable to ABO-c transplants
– Simplified protocols are emerging & thus increasing the usage of ABO-i transplants.
– Availability of many options for reducing anti-A/B antibody & to reduce the risk of hyper-acute rejection.
– Pre-& post- transplant anti-A/B antibody titers help prediction & early detection & management of AMR.
– Certain ABO blood types are less immunogenic & permit transplantation without the need for pre-transplant desensitization: A2 donation to non-A recipients (B & A2B). A2 present in 20% of blood type A in white races; & only 0.15% in Japanese.
– Splenectomy is largely replaced by rituximab in ABO-I transplant protocols to remove B-cell.
– In some case there is normal graft function & structure(accomodation) despite reemergence of anti-A/ B antibody against A or B antigen.
– Maintenance IS agents do not differ from those of ABO-C transplants (triple: CNI, MMF & steroid).
=============================================
Adverse effects & arguments against ABO-I kidney transplantation:
1. Higher immunological risks & thus intensified IS & antibody depleting therapies compared to ABO-C transplants with its known consequences:
– The infection rate is significantly higher than in
ABO-c transplants (60% vs 29.8%).
BKV was the most common viral infection (25% vs
8.5% in ABO-c- transplants).
– Limited data indicates that ABO-i is not associated
with an increasing incidence of malignancy;
however long-term observations are needed.
2. Significantly higher incidence of AMR compared to ABO-c- transplants (17.9% vs 1.1%). However no significant difference in the rate of ATCMR (48.4%
vs 35.7%).
3. ABO-i is more expensive than ABO-c transplant due to costs of desensitization & removal of anti-A/B antibody. It is, however, more cost-effective than dialysis in the
long-term & provides a better quality of life.
Well done, thank you
ABO incompatible renal transplants: Good or bad?
In the context of living donor ,who is ABO incompatible with the recipient, the patient can chose one of three options:
(1) stay on the waiting list for deceased donor KT
(2) have paired kidney donor exchange
(3) undergo ABOiKT.
According to the Organ Procurement and Transplantation Network (OPTN) report 2011, 86500 patients on the deceased donor waiting list, Almost 5000 patients died while waiting for a kidney.
ABOi transplantation was reviewed in several studies in different countries and using different desensitization protocols and induction therapy. Overall, ABOi transplantation was shown to be similar to ABO compatible on the long term graft and patient survival with cost effectiveness when comparing to dialysis.
So ABO incompatible renal transplants is Good when other options are not available. It is associated with better survival rate when comparing to a patient receiving dialysis in the waiting list. It is Bad when it is done in a patient with high risk for infection or malignancy when paired exchange kidney program is available.
Current strategies of ABOi-KT compose three common principles: (1) antibody measurement; (2) B-Cell depletion; and (3) antibody depletion.
Antibody measurement
The acceptable titer of anti-A/B antibody at the time of transplant has varied between 1:4 and 1:32 in line with the protocol of individual centers. Inclusioncriteria for isoagglutinin titer is < 1:256, no statistically significant difference between high- (> 1:256) and low titer (< 1:128) at the baseline in allograft function at 6 mo after transplantation.
B-cell depletion
Splenectomy and Rituximab: Splenectomy has been largely replaced by RIT in ABOi-KT protocols to remove B-cell
Antibody depletion
In order to eliminate existing anti-A/B antibody, plasma exchange (PE), DFPP and IA[67] are available. They differ in their mechanisms of action, specificity, efficiency and cost.
USE OF IVIG
IVIG is believed to act through various mechanisms: (1) complement down-regulation; (2) interactions with the Fc receptors; (3) inhibit of B/T-cell proliferation; (4) inhibit of CD8 T-cell cytotoxicity; and (5) increased apoptosis of B-cell.
Accommodation
anti-A/B antibody titer returns to the baseline level within almost 1 wk after KT[11,79,80], even if optimal desensitization is performed. Therefore, intense monitoring is necessary during critical first two weeks after ABOiKT.
ADVERSE EFFECT OF ABOI-KT
Infection: The infection rate in ABOi-KT is significantly higher than in ABOc-KT (60% vs 29.8%)[37]. The rates of infection including cytomegalovirus (CMV), herpes simplex virus, varicella zoster virus and BK virus (BKV).
Malignancy
several studies have demonstrated that ABOi-KT did not increase the risk of posttransplant malignancy compared with ABOc-KT.
Cost effectiveness
It is recognized that KT is a cost-effective option over dialysis
Article I
ABO incompatible renal transplants: Good or bad?
Advantages
Reducing waiting list and time
Expanding living donor pool
Improvement of patient’s prognosis
Excellent graft survival (comparable with ABOc-KT), it is a valid alternative therapy for ESKD
and the outcome of ABOi-KT has become equivalent to ABOc-KT in adult and pediatric recipients
Disadvantages
Comparative high immunological risk
Higher incidence of acute AMR
Intensified immunosuppression
Antibody depletion therapy
Increasing expenditure
Higher incidence of viral infection
I think it is a GOOD program for patients with no ABO compatible living donor, it is better than dialysis for sure with better outcome than deceased donor transplant and comparable results with ABOc KT. Continuing this program within certain conditions will allow more advancements in protocols for ABOi KT, I think if Japan did not take the lead in ABOi KT we wouldn’t have the knowledge we have today.
This review has focussed on whether ABOi- KT should be offered as a therapeutic option. Historically ABO incompatible kidney transplant- (ABOi- KT) was absolute contraindication due to risk of hyper acute rejection. Since the successful series of ABO incompatible kidney transplant has led to expansion of donor pool in short waiting list. This, however will require more extensive immunosuppression protocols. Recently the outcome of ABOi- KT is comparable to ABO compatible KT. This however involves additional risks like infections and malignancy. Cost of ABOi- KT was very high but protocols have been simplified in the last decade.
ABOi- KT will require desensitization protocols-
PLEX
IVIG
B cell depletion- Rituximab
Intense Triple immunosuppression with TAc, MMF and prednisolone
ABOi- KT- Good or Bad
Advantages
It increases donor pool thus decreasing donor W/L
Outcome of ABOi- KT is comparable to ABO compatible KT
Surgical Splenectomy has been replaced by Rituximab
Accommodation- A phenomenon in which graft rejection in avoided despite re emergence of incompatible antibodies.
Disadvantages
Higher cost
More infection risk
Risk of malignancy
Aggressive immunosuppression
Desensitisation in specialist centre and aggressivemonitoring
Higher incidence of AMR
Absence of RCTs to standardize the protocols
Usually not possible in third world countries
ABO incompatible kidney transplantation (ABOi-KT) is good but with precautions and good management as ABOi-KT has led to an expanded donor pool and reduced the number of patients with ESKD awaiting deceased kidney transplantation (KT). Intensified immunosuppression and immunological understanding has helped to shape current desensitization protocols. Consequently, in recent years, ABOi-KT outcome is comparable to ABO compatible KT (ABOc-KT)
But in ABOi-KT, there is an additional residual immunological risk that may lead to allograft damage, despite using current diverse but usually intensified immunosuppressive protocols at the expense of increasing risk of infection and possibly malignancy. Notably the cost of KT is more but when compared to chronic dialysis it is less .
When a patient with ESKD requires KT and an acceptable living donor is ABO incompatible with the recipient, the patient can currently chose one of three options:
(1) stay on the waiting list for deceased donor KT;
(2) have paired kidney donor exchange (PKDE);
(3) undergo ABOiKT.
In early cases splenectomy was indicated pretransplantation but nowadays, splenectomy has been totally abandoned and the various desensitization protocols in use are combinations of antibody removal by plasmapheresis or immunoadsorption (IA), intravenous immunoglobulin (IVIG) to neutralize preformed antibodies, B lymphocyte depletion by anti-CD20 monoclonal antibody (RIT) and standard triple immunosuppression (calcineurin inhibitor, CNI; mycophenolate mofetil, MMF; and steroid). Recently, some authors reported successful outcomes of ABOi-KT without RIT and splenectomy.
Current strategies of ABOi-KT compose three common principles:
(1) antibody measurement.
(2) B-Cell depletion.
(3) antibody depletion .
ACCOMMODATION
Without adequate anti-A/B antibody reduction and desensitization before KT, an incidence of AMR and irreversible damage cannot be avoided. Successful ABOi-KT requires the reduction of anti-A/B antibody titers against ABO antigens on the graft at the time of KT. However, anti-A/B antibody titer returns to the baseline level within almost 1 wk after KT even if optimal desensitization is performed. Therefore, intense monitoring is necessary during critical first two weeks after ABOiKT. Accommodation is defined as a phenomenon whereby graft rejection is avoided despite reemergence of incompatible antibody.
CURRENT PROTOCOL OF ABOI-KT
In ABOi-KT, intensified immunosuppressive protocol usually starts before KT in order to deplete anti-A/B antibody. . RIT has been adopted in the place of splenectomy by majorities of centers. However, the timing and dose of RIT administrated remains variable. RIT or splenectomy-free protocols have successfully, used low dose IVIG after plasmapheresis. Postoperative IAs is not performed routinely and its use is determined by antibody titers. Maintenance immunosuppressive agents are mostly triple agents which are CNI, MMF and steroid. Tacrolimus is the CNI of choice in these ABOi-KT protocols. MMF was taken 7-14 d pretransplant in order to inhibit antibody production. Some centers use a protocol without daclizumab, basiliximab or antithymocyte globulin, and report excellent outcomes. Thus it is controversial whether these clonal antibodies should be introduced in ABOi-KT or not.
ADVERSE EFFECT OF ABOI-KT
COST OF ABOI-KT
It is recognized that KT is a cost-effective option over dialysis
ABO incompatible renal transplants: Good or bad?
previously ABOI kidney transplant was contraindication due to the risk of hyper acute rejection, the experience with ABOI KTX comes from Japan when they use ABOi KTX program in LD earlier when there is no access to DD program ,and they confirmed its effectiveness with comparable graft survival to ABOc KTX by many observational studies with modification of desensitization protocols over time and better understanding of immunology nowadays ABOI- transplantation practiced in many centers in US and Europe with very acceptable outcome .So ABOI-KT is good, helped in reduce the waiting list and time with expanding the pool of donor access in LD program, and associated with better patient’s prognosis compared to waiting on dialysis and have similar graft survival to ABOc KT, also ABOI KT is cost effective.
Desensitization protocols for ABOI kidney transplantation evolving over time, yet not standardized, each center have their own protocol based on their experience, facilities, resources and infrastructure .
PLasmaphersis , DFPP,IA:
By principle the concept of desensitization based on antibodies removal by plasmapheresis (plasma exchanges, non-specific associated with removal of abs , antiviral ,antibacterial Igs and clotting factors with increased rate of infection, coagulopathy , bleeding tendency the use of immunoadsorption (IA) which is more selective and specific , preferred for HLA I , ABOI transplant with specific removal of anti-A,anti B abs with average reduction rate by 3-4 fold and associated with less infectious or bleeding side effects compared to plasma-exchange but more cost
Immunomodulating agent IVIG:
have pleotropic effects including complement inhibition , FC receptors binding, inhibit B and T cells proliferation, CD8 T cell inhibition, with B cells apoptosis
No standardized dose, high dose, low dose usually given after plasmapheresis many side effects including infusion related allergic reaction, risk of thromboembolic events, AKI, its use in combination with plasmapheresis the preferred and widely used protocol with or without Rituximab.
B cell depletion:
B cell depletion earlier protocols including surgical splenectomy which have been replaced by B cell depleting agent anti-CD 20 monoclonal AB, rituximab with different doses and frequency based on local center protocols but trend nowadays to use low dose rituximab usually 10 days pre operative again its part of intense immunosuppressive therapy associated with higher risk of infection like CMV, BKV, PJP.
Triple intense immunosuppression:
standard triple therapy in ABOI KTX have been moved over time from cyclosporine based to tacrolimus based with full dose MMF and prednisolone, pre transplant 2-4 weeks and continue as maintenance triple IS after transplantation , some centres tried early steriod withdraw after 1week with 100% graft survival .
Antibodies measurements:
Measurement of anti-A/anti B titers before and after ABOi transplantation is very important by Using different methods with no standardization among laboratories but flowcytometry is the more preferred and more accurate method but its use limited by cost and availability compared to tube technique, gel technique , The higher antibodies titer and the rapid rebound in first two weeks associated with higher rate of AMR and graft loss so its mandatory to continue post-transplant frequent monitoring for antibodies formation in first two weeks .
C4D staining positive in ABOI alone its common finding and indicate graft accommodation , for the diagnosis of AMR post ABOI KTX we need the combination of confirmed graft injury , C4D staining and ABS detection.
ABO incompatible renal transplants: Good or bad?
Generally its good but nothing good 100% so it has also some pitfalls so it should be considered in special circumstances, therefore any recipient with an incompatible living donor should choose from three options.
(1) stay on the waiting list for deceased donor KT.
(2) have paired kidney donor exchange (PKDE).
(3) undergo ABOiKT
ABOiKT is a viable alternative to waiting on deceased donor list.
There are some merits and demerits for ABOiKT.
ABOiKT kidney transplantation has merits like:
-Saving many chances for kidney recipients .
-Increase the donor pool and so decreasing the donor waiting list.
-The outcome of graft survival in ABOiKT has been similar to ABOc-KT.
-Medical splenectomy (Rituximab) replaced surgical splenectomy.
(splenectomy-free protocols).
-ABOiKT become in progress currently because the protocols become more simplified and clear than before and due to its good graft and patient survival outcome.
ABOi kidney transplantation has demerits like:
-Challenges facing incompatible ABO transplantation and require new strategies.
-Heavily immunosuppressive protocol and desensitization, there are high risk of infection and malignancy.
– ABOi-KT had a significantly higher incidence of AMR compared to ABOc-KT without difference in ACR.
-Serial follow up of Isoagglutinin pre and post transplantation.
-Costly desensitization protocol specially for developing countries.
ABO incompatible renal transplants:good or bad ?ABOi is good for these reasons:
1- lead to an expand donor pool and reduced the number of patients with ESRD awating deceased kidney transplant.
2- improved graft and patients survival compared whom spend waiting time long in dialysis and even with ABO c-KT.
3- KPDE for HLA (sensitize and or ABOi so create more compatible pairs so KPDE is low immunological risk ,avoid intensified immunosupression and cost effects.
4-Over come the shortage of deceased donor in some countries such as japan,
5-using Rituxmab in desensitization protocol useful for both AMR and CAMR prevention so observed that ABOi -KT with RITUXMAB has stasticly significant lower rate of CAMR at 2 year post transplant than ABOc-KT (3.5% versus 28.9%) .
6- accommodation phenomena so minimize the risk of immunosupression and in ABOi -KT here it remain speculative.
7- although in presence of heavy immunosupression medication the risk of malignancy same as ABOc-KT .
ABOi -KT is bad as for :
1- intensified immunosuppression
using plasmapharasis with risk of all complication such as infection ,bleeding,hypocalecimia and hypo tension.
2- higher incidence of infection such as viral infection(CMV,EBV).
3- higher incidence of AMR due to anti A/B antibodies but no difference in acute cellular rejection compared with ABOc-KT.
4- increasing expenditure.
5-Antibody depletion therapy
6- using IVIG with all complication and other hand absence of control data ,the use of IVIG in ABOi-KT can best described as empirical.
7-absence of randomized trials to satisfy about different protocol.
8- ABOi-KT had sever transplant glommulapathy than ABOc -KT without HLA Ab at 1 year post transplant.
9- can not be implement in poor countries more expensive than ABOc-KT.
10- desensitization is require special centre with full filled criteria and need lab to monitor anti A/B antibodies titre so usually not available in all center as equipment is expensive
Good
Graft survival is similar to ABO compatible transplant,
Increase number of potential living donors
Reduce waiting time on dialysis
Provide better quality of life than dialysis
More cost effective than dialysis on the long-term
Bad
It is associated with higher immunological risk
It requires close monitoring of anti-ABO antibody titer before and after kidney transplant to detect any rebound in antibody production.
Increased risk of AMR
Several complication associated with treatments used for antibody depletion as plasmapheresis increase risk of bleeding and infection.
Immunoadsorption may be needed to reach acceptable titer but with high cost and is not available in all centers.
Needs intensified immunosuppression protocols
No available randomized controlled trials studying different immunosuppressive agents or the long term outcomes
Increased risk of post transplant infection.
It is a good chance for patients who can’t find a compatible donor nor participate in kidney paired donation, also it is better than remaining on dialysis. However, it is difficult to be applied due to the increased cost and higher immunological risk.
I think it’s very good option for our country which doesn’t have a deceased donor programe or even PKD. It will definitely will increase the donor pool and many patients who otherwise will remain on dialysis will get a transplant.
The quality of dialysis in many third world countries including mine is not good so one should be very careful in interpreting dialysis survival data for such patients (as most of data is western or American etc). So We have to decide is it better to keep someone on poor quality dialysis or go for ABOi transplant?
It’s good because less waiting time and list
Improve quality of life rather than stay for long time on dialysis or dying while waiting for deceased donor
it’s give chance for paired kidney donor exchange with low immunological risk and benefit to get compatible donor
Good graft survival in comparison to ABO compatible
it’s Bad because high immunological risk
it’s very expensive for monitoring anti A/B antibodies titer and invasive method for removing antibodies by plasma exchange or immunoadsorption for removal B and T cell and risk to protocol of renal biopsy every 3 months
Risk to hazard of intensive immunosuppressive drug
High incidence of infection and malignancy
High risk of rejection
GOOD
Bad
Thank you
What is your personal opinion, good or bad?
Will you support this programme or you implement it under certain conditions?
Is it good or bad and why?
Why good ?
Why bad ?
Thank you
What is your personal opinion, good or bad?
Will you support this programme or you implement it under certain conditions?
it is good and reasonable option for transplantation:
1- it is better to wait for NDD or DCD
2- in spite of high cost of desensitization protocol, it is less cost than the cost of staying on dialysis.
3-it allows to enlarge donor pool and allow more patient to leave dialysis and become transplanted so help to decrease cardiovascular mortality on dialysis.
4-same incidence of AMR between ABO incompatible and compatible donor transplantation
5- same risk of malignancy
6-desensitization protocol can be individualized to try to decrease cost
7-rituximab as a part of induction and also it replace surgical splenectomy
8- the concept of accommodation
BUT
1- we lack RCTs to judge well is it good or not
2-definite we face a problem of increase incidence of infection either bacterial or viral like CMV, BK…as a complication of heavy immunosuppression.
Thank you Riham for your reflection. You mentioned an important point that ABOi transplantation is cheaper than dialysis. Can you prove this point please for us and provide evidence.
COST OF ABOI-KT It is recognized that KT is a cost-effective option over dialysis[104-106]. The estimated cost for ABOi-KT over 20 years was $315600, which was approximately 15% lower than dialysis[107]. ABOi-KT is more expensive than ABOc-KT because of requirement for desensitization and removal of anti-A/B antibody. The cost of ABOi-KT in the first 90 d posttransplant is $90300 compared to $52500 for ABOc-KT[108]. The additional cost of ABOiKT amounts to €31948 for IAs, RIT, IVIG, and prolonged hospital stay[31]. The cost of single IA is approximately €4340-1433[40]. However, despite more expensive, ABOi-KT is still more cost-effective than dialysis in the long-term and delivers a better quality of life.
this is from same paper
but i mean that ABOI transplant on long term will be cost effective in comparison to the burden of dialysis and its cost and also the cost of its complication beside better quality of life post transplant in comparison to stay on dialysis
Although renal transplantation is the treatment of choice for patients with ESRD, but it had big obstacle which is the shortage of donor pools ( deceased & live). ABOi-KT can reduce the waiting time for those patients. It is a good option because :
Thank you, Ban for your answer. You mentioned an important point that ABOi transplantation is cheaper than dialysis. Can you prove this point please for us and provide evidence.
Estimated cost of ABOi-T over 20 years ~$315600 which is 15%lower than cost of dialysis & ABOi-T provide better quality of life.
The good side of ABOi KT is that it expanded donor pool and reduced the number of recipents awaiting deceased kidney transplantation ie decreasing waiting time list.
The outcome of ABOi-KT has been comparable to ABOc-KT in adult and pediatric recipients.
ABOi cases can be enrolled into Paired kidney donation exchange PKDE programs either through three-way, four-way and domino paired donation which has advantages having less immunological risk, needs less immunosuppression, and is cost effective if compared with dialysis and also provides better quality of life.
For blood group A ;A2 kidney is less susceptible to have antibody rejection in the presence of anti-A antibody. Non-A recipients receiving kidneys from A2 donors can safely accept the transplantation because A2 antigen expression is weaker than A1.
ABOi-KT preoperative management includes:
(1) antibody measurement mainly through flowcytometry ,tube and gel technique.
High preoperative anti-A/B IgG titers correlates with poor long-term allograft survival in ABOi-KT
(2) B-Cell depletion by splenectomy because it decreases the risk of antibody mediated rejection but this was not confirmed because rejection occurred after splenectomy, currently it is replaced by Rituximab, Rituximab is used in AMR, and in chronic antibody-mediated rejection (CAMR) prevention.
(3) antibody depletion by plasma exchange,DFPP, immunoadsorpant,the latest is more effective with less side effects but is more expensive and IVIG is usually used after plasmapheresis to avoid AMR
Accommodation is a mechanism where graft rejection doesnot occur inspite of reappearnance of incompatible antibodies.
The Eurotransplant protocol is IAs followed by high dose of IVIG then triple immunosupreesion with Tac ,MMF ,and steroids.
The bad side of ABOi-KT, is seen in the superadded immunological risk that can cause allograft damage, inspite of intensified immunosuppressive protocols increasing risk of infection and malignancy.
Also desensitisation increased the expenses of the transplantation
As in splenectomy a B cell depletion method , patient is susceptible for life threatening sepsis and infection with encapsulated organisms and he will need lifelong prophylaxis as well as it’s surgical complications ,currently splenectomy free protocols are used
ABOi-KT had more severe TG than ABOc-KT without HLA antibody at 1 year posttransplant
ABOi-KT had a significantly higher incidence of AMR compared to ABOc-KT on the other hand ,some studies showed no difference .
The rates of infection including mostly BK virus (BKV), cytomegalovirus (CMV), herpes simplex virus, and varicella zoster virus in ABOiKT were significantly higher than in ABOc-KT
Some studies mentioned that ABOiKT is not associated with an increased incidence of malignancy after KT but long term studies for ABOiKT after rituximab treatment is needed
Thank you
What is your personal opinion, good or bad?
Will you support this programme or you implement it under certain conditions?
Yes I support this program it’s advantages outweigh it’s disadvantages
– I think it’s a good option if failed paired kidney donation or if it is unavailable
– It is better compared with waiting for a deceased donor or being on dialysis for a long time
– Why?
But
– Careful monitoring and suspicion for viral infection especially BK virus
Very impressed Radwa. You put your own reflection very clear. Your summary is very short and up to the point. I agree with every single word you mentioned.
Good
Leads to increase in donor pool
decrease in donor waiting list time .
outcome of ABOi-KT has become equivalent to ABOc-KT in adult and pediatric recipients.
Improvement of patients prognosis
Better quality of life for the patient.
live donor ABOi-KT is a viable alternative to waiting on
deceased donor list.
Bad
Higher incidence of AMR (17.9%)
Comparative high immunological risk.( acceptable titre of antibody pre transplant not clearly defined and also the protocol is not standardised)
Intensified immusuppresion , pre transplant rituximab, plasmapharesis/DFPP/IAs with post IvIg needed.
Increased cost of transplant initially ( additional cost for IAs, RIT, IVIG is 31948 pounds, however more cost effective than dialysis in the long term( 15% lower cost as compared to remaining on dialysis for 20 years.)
Higher incidence of viral infections like CMV,HSV, Varicella zoster and BK virus which is most common(25%).