Based on this article, will you accept performing desensitisation of highly sensitised transplantation after running out of all options? Any survival advantage (graft and patient)?
will you accept performing desensitisation of highly sensitised transplantation after running out of all options?
Yes.
Desensitization became less attractive if the patient had a better option (e.g. paired kidney donation). Nevertheless, desensitization may be the only option for a group of highly sensitized recipients who have no alternative options except to continue on dialysis while they are on the waiting list.
Montgomery, et al. 2011. Documented a significant survival advantage for those transplanted after desensitization compared to patients who continued on dialysis (1). The patient survival for recipients of kidney allograft after desensitization was 90.6% at 1 year, 85.7% at 3 years, 80.6% at 5 years, and 80.6% at 8 years, as compared with rates of 91.1%, 67.2%, 51.5%, and 30.5%, respectively, for patients in the dialysis-only group and rates of 93.1%, 77.0%, 65.6%, and 49.1%, respectively, for patients in the dialysis-or-transplantation group (P<0.001 for both comparisons).
References:
1) Montgomery RA, Lonze BE, King KE, et al. Desensitization in HLAincompatible kidney recipients and survival. N Engl J Med 2011; 365: 318.
yes we can accept the desesitisation therapy in very highly sesensitized candidate as its still assocaited with better early graft and patient survival compared to longwaiting on dialysis but with in 5 years the risk of chronic rejection , Tg and graft loss increased up to 55% in the presence of denovo DSA , that why the frequent DSA s monitoring post transplant and timely treating AMR considered one of the important fcators that can improve thelong term graft survival.
If KAS and paired exchange program both failed ,I would accept, as despite higher rate of AMR, all patients experienced similar graft survival with a median follow up time of 2.9 years. However the 5 year graft and patient survival was worse in those undergoing desensitization vs HLA comparable transplants. Despite all the adverse prognosis,I think it’s still better than the prognosis related to regular hemodialysis.
YES, keeping in mind that Desensitization is a last resort taking into account that favorable outcome relies on aggressive posttransplant Abs monitoring and protocol biopsies to identify patients with higher risk of rejection and
Vo AA, Haas M, Huang E, et al. Clinical relevance of post-transplant
donor specific antibodies (DSAs) in patients receiving desensitization
for HLA incompatible kidney transplantation. In press.
after running out of all options, yes we can accept to do desensitization and transplantation after it for better quality of life than staying on dialysis, of course survival of graft will be better than not doing desensitization and the patient survival is better than staying on dialysis, but we should close monitor DSA after transplantation
Based on this article
Yes i would accept to do desensitization as it remains a good way to access transplantation for highly sensitized recipients when there is no other available options and still better option than waiting on dialysis.
*Close follow up of DSA and protocol biopsy of desensitization transplanted patients with early detection of subclinical AMR with early treatment may help to improve graft outcome and patient survival.
*Careful patient selection, which involves the identification of individuals who can withstand desensitization treatment and have favorable antibody profiles amenable to successfully overcoming the incompatibility to allow transplantation, remains the cornerstone desensitization.
*Patients with DSA and T-cell activation as demonstrated by high levels of soluble CD30 (sCD30) in pretransplant serum have a threefold higher risk of graft loss than patients with DSA but low sCD30 levels . Using this and other novel biomarkers to follow treatment response in addition to traditional DSA MFI/titer measurement may offer additional guidance into management before and after transplantation.
Vineeta Kumar and Jayme E. Locke.New Perspectives on Desensitization in the Current Era – An Overview.Front. Immunol., 30 July 2021 |
will you accept performing desensitisation of highly sensitised transplantation after running out of all options?
Yes. In those highly sensitized patients who do not have a living donor, are not eligible for paired exchange program, and have along expected waiting period, desensitization should be performed as data has shown a definite survival advantage.
Any survival advantage (graft and patient)?
Data from US showed a definite advantage of HLA incompatible transplant after desensitization (as compared to remaining on wait-list) with reference to patient survival at 1,3,5 and 8 years with it being as high as 1.75 times more by 8 years post-transplant (76.5% versus 43.9%). (1)
Although, the data from UK shows that there is no survival benefit and the results are comparable in the 2 groups. (2)
Reference: 1) Orandi BJ, Luo X, Massie AB, Garonzik-Wang JM, Lonze BE, Ahmed R, Van Arendonk KJ, Stegall MD, Jordan SC, Oberholzer J, Dunn TB, Ratner LE, Kapur S, Pelletier RP, Roberts JP, Melcher ML, Singh P, Sudan DL, Posner MP, El-Amm JM, Shapiro R, Cooper M, Lipkowitz GS, Rees MA, Marsh CL, Sankari BR, Gerber DA, Nelson PW, Wellen J, Bozorgzadeh A, Gaber AO, Montgomery RA, Segev DL. Survival Benefit with Kidney Transplants from HLA-Incompatible Live Donors. N Engl J Med. 2016 Mar 10;374(10):940-50. doi: 10.1056/NEJMoa1508380. PMID: 26962729; PMCID: PMC4841939. 2) Manook M, Koeser L, Ahmed Z, Robb M, Johnson R, Shaw O, Kessaris N, Dorling A, Mamode N. Post-listing survival for highly sensitised patients on the UK kidney transplant waiting list: a matched cohort analysis. Lancet. 2017 Feb 18;389(10070):727-734. doi: 10.1016/S0140-6736(16)31595-1. Epub 2017 Jan 6. Erratum in: Lancet. 2017 Feb 18;389(10070):700. PMID: 28065559.
proceeding with desensitization for those highly sensitized patients where paired exchange is not possible and expected wait time is considered unacceptable, may be a reasonable consideration. desensitization was found to be associated with better early graft and patient survival compared to longwaiting on dialysis .
If it is the only option , I can accept desensitization as QOL will be better than long stay on dialysis, but with caution regard:
_ close and regular follow up of DSA to detect ant rejection episodes early.
_ use protocol biopsy to detect subclinical rejection.
_ screening for malignancy which increase in the context of highly suppressive therapy .
Inspite of high rates of AMRs & TG, I will strike a balance & proceed to desensitization only in highly sensitized patients without living donors, where paired exchange is not feasible & would likely unacceptably prolong wait time.
yes, After exhausting all other options, we decided that doing desensitization and transplantation afterwards would provide a better quality of life than remaining on dialysis. Of course, the graft’s survival will be better than not doing desensitization, and the patient’s survival will be better than remaining on dialysis.
Survival advantage of de-sensitization is a subject of debates at the moments. Two studies examined this matter one in US and the other one UK. US study showed survival advantages compared to wait list group, while no difference among de-sensitized & wait list. Possible explanations are ;
I would proceed with desensitization for those highly sensitized patients without living donors, where paired exchange is not possible and expected wait time is considered unacceptable
The survival benefit still better than prolong dialysis but the ABMR or chronic allograft rejection might be between 25-50%. It is still a risk to take, but in my opinion, its a better risk to take than being longer with dialysis.
Yes, it is better than keeping the patient on dialysis, as the survival rate is higher in transplanted patients, but still, the long term patient and graft survival is lower in desensitized patients as compared to HLA-compatible transplant recipients
Sure patient survival is better with transplantation if compare with those patient stay on hemodialysis .
regarding graft survival of high sensitize patient ,although short term (one year )graft survival the same for non sensitized but 5 year graft survival inferior to non sensitized group.
Based on this article, will you accept performing desensitisation of highly sensitised transplantation after running out of all options?
Any survival advantage (graft and patient)?
Yes , I will accept desensitisation as best option in highly sensitised patient after running out of all option ( paired exchange scheme ) instead of being on waiting list for long period or long-term dialysis.
Also associated with better early graft and patient survival than long-term dialysis,but increase risk of chronic rejection, transplant glomerulopathy and graft loss up to 55% due to development of de novo DSA WHICH NAKE FREQUENT MONITORING OF DSA POST-TRANSPLANT IS NECESSARY .
yes sir
in spite of being highly sensitized patient has higher rate of ABMR (ABOUT 30%) with lower patient and graft survival, the outcome is more worse by remaining on HD PROGRAM.
Balaji Kirushnan
2 years ago
The original article by Vo et al is an observative prospective study for which the level of evidence of 2…The above is an expert commentary on the same, so the level of evidence becomes 5
The article highlights the importance of desensitization in kidney transplants in the
United States…Over the past 2 decades the kidney transplant patients rates have improved because of the Kidney Allocation system where in the wait list of the recipients in the US have been given points and 4 points are awarded if their cPRA >80%. This improved the waiting time of those highly sensitized patients from 19 years to 3.2 years…The second development was the development of National Registry for paired kidney exchange program which has facilitated the kidney transplant for patients without desensitization…These 2 programs have lead to the overall decline in the rate of desensitization program…Nevertheless desensitization program allows the transplant of patients who are on the waiting list for a long time and do not get a kidney. Infact the survival rate of HLAi Renal transplant after desensitization is better than waiting on the hemodialysis waiting list at 1 year, 2 years and 5 years…
In this study they have described a cohort of 90 patients who are highly sensitized, who underwent pre transplant aggressive desensitization protocols and followed them later…the conclusion was that highly sensitized patients may develop AMR in the post operative period as de novo DSA develop in these individuals and AMR can develop later in them…But they have reported comparable short term benefit among the sensitized and the non sensitized patient groups….But other data are not similar..Data from Mayo clinic show worst transplant outcomes in terms of more transplant glomerulopathy and AMR in HLAi Transplant…The limitation of the study by Vo et al was that all were limited to deceased donor renal transplants only…
In general, the take home message would be that transplant for highly sensitized renal transplant patient should have an individualized approach…the risks of mortality waiting on hemodialysis should be weighed against transplant with anti HLA antibodies…The first option should be HLA compatible donor. If not available, transplants should be counselled for ABOi renal transplants. Kidney Allocation systems are not well developed in many developing countries, hence HLAi renal transplants may still be a better bet in these group of patients…Paired kidney exchange program also offers a better advantage when compared to desensitization but the waiting time should not get prolonged for more than 2 to 4 years when the mortality rates of dialysis takes over…
Alyaa Ali
2 years ago
It is better to avoid desensitization due to its hazards ( over-immunosuppression ,infection malignancy , high cost ) if the patient has alternative option as kidney paired donation.But, if the patient has no other option , proceed to kidney transplant with desensitization some study show a survival advantage for patients undergoing desensitization followed by live donor transplantation compared with those waiting for a compatible organ offer, and still on dialysis.
highly sensitized patients may bene!t from desensitization and that the success of these programs relies on aggressive posttransplant antibody monitoring to identify those patients at higher risk for rejection and graft loss.
Wee Leng Gan
2 years ago
Desensitization in Kidney Transplant: A Risky (but Necessary?) Endeavor for Those with Limited Options.
This is a narrative review with level 5 evidence for the clinical approach for transplantation among highly sensitized recipients. First enrol highly sensitized recipients into pair kidney transplant exchange program. Change for the allocation in the kidney Allocation System ( KAS ) by prioritized organ offers for patients with high levels of anti-HLA sensitization. Change in KAS involve intensive desensitization protocol for highly sensitize recipient. However, we should assess patients and counsel regarding the risks and benefits for continuing renal replacement therapy or proceed with desensitization protocol. Regular DSA monitoring and protocol allograft biopsy should be performed for early detection of graft rejection so that prompt action can be taken. IVIG, rituximab, Plasmapharesis, tocilizumab, stratified by donor-specific antibody (DSA) status at the time of and following transplant.
Based on this article, will you accept performing desensitisation of highly sensitised transplantation after running out of all options? Any survival advantage (graft and patient) I would first arranging multidisciplinary counselling session with potential recipient who is highly sensitised. Explain the possible risk for continue long term dialysis and proceed with transplantation in highly sensitized recipient. Financial support for potential recipient should be explore as transplantation among highly sensitive individual involve complicated and expensive desensitization treatment and high risk of allograft rejection. I would accept performing desensitization if patient has exhausted other compatible kidney pair program. Successful desensitization recipient has a good graft survival. However, risk of AMR post-transplant is estimated 25-50%.
Nandita Sugumar
2 years ago
Take home message
Donor pool is scare for organ transplant in the world. Added to this, sensitized patients find it even harder to get a suitable donor.
Kidney allocation systems based on prioritizing sensitized patients and Kidney paired donation schemes have improved the chances of highly sensitized patients getting suitable donors.
Desensitization is used for good outcome in highly sensitized patients. However, these treatments are excessive and require a lot of resources. Hence, other options if available should be explored, such as KPD schemes.
Desensitization is done using a combination of IVIG, rituximab, PLEX, tocilizumab with careful DSA monitoring.
However, DSA monitoring and desensitization does not essentially prevent occurence of AMR in the patients. Significant risk of tubular injury, transplant glomerulopathy and subsequent graft failure remain.
Paired exchange is better because of more appropriate donor, reducing the risks that come with HLA incompatible transplant.
Desensitization can be considered in patients who have been on dialysis and waiting list without any chance of suitable living donors even with paired donation.
Level of evidence
This article is a narrative review. Level of evidence 5.
ahmed saleeh
2 years ago
Desensitizing treatments are expensive, resource intensive, and place patients at risk for morbidity associated with potent immunosuppression.
These treatments remove circulating antibody or temporarily inhibit antibody production without signicant effect on immunologic memory. As such, there is a well-documented memory immune response following HLA-incompatible transplant, with postdesensitization antibody-mediated rejection (AMR) rates generally ranging from 25% to 50%.
Desensitization to facilitate deceased donor transplant is arguably a more challenging hurdle due to the lack of predictable transplant events.
The best option would be to avoid HLA-incompatible transplant whenever possible, although not necessarily at the expense of signicantly prolonged dialysis exposure while awaiting a compatible offer
Due to the kidney allocation system (KAS) and national paired exchange programs such as the National Kidney Registry enthusiasm (and need) for desensitization of highly sensitized patients has decreased in recent years.
Manal Malik
2 years ago
2-Desensitiztion in kidney transplant=A risky (but necessary) What is the take-home message advised by this article?
Highly sensitized patients without living donors where pared exchange is not possible and expected wait time is considered unacceptable so proceeding with desensitization may be reasonable consideration
So those patients at the highest risk of posttransplant immunologic injury following desensitization and emphasizes the importance of careful antibody maintaining throughout the post renal transplant period.
Despite aggressive postrenal transplant DSA monitoring in the current report VO et al, histological identified AMR was detected in 29% of sensitized recipients.
If living donor are available, paired exchange should be considered to avoid cost and risk of desensitization therapy.
2- level of evidence of this article is 5
Abdullah Raoof
3 years ago
What is the take-home message addressed by this article?
1- it is important to avoid transplantation of highly sensitized patient ,this can be achieved by
a- kidney allocation system (not available in my country)
b- kidney paired exchange (not available in my country)
by these two system the better compatible (donor-recipient ) can be found
if it is not desensitization and then transplantation has better patient and graft outcome than remaining on HD program .
although desensitization has its own risk (infection ,malignancy ,hypocalcemia ,coagulopathy) and high cost .
What is the level of evidence provided by this article?
(expert opinion ) level 5
AMAL Anan
3 years ago
What is the take-home message addressed by this article?
* Highly sensitised patients undergoing desensitisation with living donor if failed pair exchanged than being on waiting list and carrying hazard of long term dialysis.
* Desensitisation treatment may be expensive, resource intensive and place patient at risk for morbidity associated with potent immunosuppression, although this treatment remove circulating antibody or temporarily inhibit antibody production without significant effect on immunological memory.
AMAL Anan
3 years ago
What is the level of evidence provided by this article?
Level v expert opinion
CARLOS TADEU LEONIDIO
3 years ago
What is the take-home message addressed by this article?
From this article, we can reflect on the gains that can exist with the risks and gains of desensitizing a patient. The desensitization allows the recipient to receive an organ from a deceased donor with acceptable risks of graft rejection.
This involves higher costs, however it seems to be a final strategy for those patients who, even after the change to the kidney allocation system (KAS) and the increased use of national paired exchange programs, are unable to obtain an organ donation.
There is greater risk for long-term graft loss, but acceptable. More fearful seems to be the increased risk of opportunistic infections for patients.
What is the level of evidence provided by this article?
This is not a study, this is a opinion expert – level evidence 05.
Drtalib Salman
3 years ago
–What is the take-home message addressed by this article?
we should have enthusiasm to establish kidney allocation system (KAS)and national paired exchange program in our country to give access for highly sensitizing patient for transplantation with less cost and short waiting time.
What is the level of evidence provided by this article?
level 5
MOHAMED Elnafadi
3 years ago
the take home message is desensetization is an available option for patients who fail to have aliving donor or waiting so long on dialysis .
Desensitization treatments remove circulating antibody or temporarily inhibit antibody production without significant effect on immunologic memory.
also desenstization carry the risk of infection malignancies added to high cost.
kidney allocation system and paired exchange programs have increased chances of such patients receiving a compatible kidney, thereby having a positive impact on the graft survival.
level v
Asmaa Khudhur
3 years ago
Desensitizing treatments are expensive, resource intensive, and place patients at risk for morbidity associated with potent immunosup- pression. Furthermore, these treatments remove circulating antibody or temporarily inhibit antibody production with- out significant effect on immunologic memory. As such, there is a well-documented memory immune response fol- lowing HLA-incompatible transplant, with postdesensiti- zation antibody-mediated rejection (AMR) rates generally ranging from 25% to 50%.
highly sensitized patients may benefit from desensitization and that the success of these programs relies on aggressive post- transplant antibody monitoring to identify those patients at higher risk for rejection and graft loss.
survival advantage was attributed to desensitization before living- donor transplant.
Vo et al7 have reported favorable results both in achieving transplant as well as acceptable posttransplant outcomes in desensitized patients receiving deceased donor transplants.
Despite aggressive posttransplant DSA monitoring in the current report by Vo et al, histologically identified AMR was detected in 29% of desensitized recipients.
the best option would be to avoid HLA-incompatible transplant whenever possible, although not necessarily at the expense of significantly prolonged dialysis exposure while awaiting a compatible offer.
When living donors are available, paired exchange should be attempted in order to avoid the cost and risk associated with desensitizing therapy as well as the posttransplant immune response that will likely translate into poorer long-term graft survival.
Changes in KAS have helped to increase rates of deceased donor transplant for some but not all highly sensitized patients.11 Thus, proceeding with desensitization for those highly sensitized patients without living donors, where paired exchange is not possible and expected wait time is considered unacceptable, may be a reasonable consideration.
Paired exchange options should be exhausted, and a realistic estimate of wait time taking into account priorities for high cPRA patients under KAS should be considered. With this in mind, the current study by Vo et al provides an important guide for clinicians to identify those patients at the high- est risk of posttransplant immunologic injury following desensitization if one chooses this route and emphasizes the importance of careful antibody monitoring throughout the posttransplant period.
What is the take-home message addressed by this article? -Highly sensitized patients can proceed in transplant after desensitization or paired kidney exchange and transplant better than staying in waiting list. – Desensitization removing the circulating antibodies or inhibiting production of antibodies with no affection on immunological memory
Level v expert opinion
Dalia Ali
3 years ago
2 important developments have signicantly improved access to transplant for highly sensitized patients
1-kidney allocation system (KAS) in December 2014 prioritized organ offers for patients with high levels of anti-HLA sensitization. As a result, the median waiting time for highly sensitized patients with cPRA of 98%–100% has decreased from >19 years to 3.2 years
2-national paired exchange programs considered the best initial options for patients with either ABO or HLA-incompatible living donors.
So, desensitization of highly sensitized patients has decreased in recent years
Desensitizing treatments are expensive, resource intensive, and place patients at risk for morbidity associated with potent immunosuppression. Furthermore, these treatments remove circulating antibody or temporarily inhibit antibody production without signicant effect on immunologic memory. As such, there is a well-documented memory immune response following HLA-incompatible transplant, with postdesensitization antibody-mediated rejection (AMR) rates generally ranging from 25% to 50%.
Despite aggressive posttransplant DSA monitoring histologically identied AMR was detected in 29% of desensitized recipients
best option would be to avoid HLA-incompatible transplant whenever possible, although not necessarily at the expense of signicantly prolonged dialysis exposure while awaiting a compatible offer. When living donors are available, paired exchange should be attempted in order to avoid the cost and risk associated with desensitizing therapy as well as the posttransplant immune response that will likely translate into poorer long-term graft survival.
proceeding with desensitization for those highly sensitized patients without living donors, where paired exchange is not possible and expected wait time is considered unacceptable, may be a reasonable consideration. When considering this option, however, one should account for the published variability in both postdesensitization transplant rates as well as outcomes.
Desensitization in Kidney Transplant: A Risky (but Necessary?) Endeavor for Those with Limited Options
Expert opinion, Level 5 evidence
Advances in transplanting highly sensitized patients had made improvement in transplant access:
1. change to the kidney allocation system (KAS) – prioritized organ offers for patients with high levels of anti-HLA sensitization.
· So, the median waiting time for highly sensitized patients with cPRA of 98%–100% has decreased from >19 years to 3.2 years
· Europe- focusing on organ allocation to sensitized patients based on acceptable mismatches has succeed in transplanting >1000 patients with excellent long-term outcomes
2. increased use of national paired exchange programs such as the National Kidney Registry
Data suggest that prior to KAS system – survival advantage for patients undergoing desensitization followed by live donor transplantation compared with those waiting for a compatible organ offer
But desensitizing treatments are expensive, resource intensive, and place patients at risk for morbidity associated with potent immunosuppression
Vo et al suggested:
· 90 highly sensitized patients undergoing desensitization with IVIG, rituximab, +/PLEX/tocilizumab, stratified by DSA status at the time of and following transplant
· AMR in patients with persistent pretransplant and posttransplant DSA (45%) and in patients who developed de novo DSA but were DSA negative at transplant 70%, compared with those with pretransplant DSA that disappeared (11%) or those with no DSA pretransplant or posttransplant (10%)
· all patients experienced similar graft survival with a median follow-up time of 2.9 years
· Conclusion- highly sensitized patients may benefit from desensitization and that the success of these programs relies on aggressive posttransplant antibody monitoring to identify those patients at higher risk for rejection and graft loss
· reported favourable results both in achieving transplant as well as acceptable posttransplant outcomes in desensitized patients receiving deceased donor transplants
other centres have failed to replicate these encouraging results using similar strategies
5-year data from the Mayo Clinic show significantly worse patient and graft survival in those undergoing desensitization versus HLA compatible transplant, as well as protocol biopsy-detected transplant glomerulopathy in 55% of desensitized versus 7% of HLA-compatible recipients
So, best option would be to avoid HLA-incompatible transplant whenever possible. Living donors are available, paired exchange should be attempted
Proceeding with desensitization for those highly sensitized patients without living donors, where paired exchange is not possible and expected wait time is considered unacceptable, may be a reasonable consideration
If decided for desensitization, paired exchange options should be exhausted, and a realistic estimate of wait time taking into account priorities for high cPRA patients under KAS should be considered
Ben Lomatayo
3 years ago
Desensitization is a dangerous business but important for those patients without hope
Highly sensitized patients
Paired exchange is not possible
Wail list time is not acceptable
2.Once we opted for desensization, we need aggressive post-transplant mornitoring for DSA for the possibility post-desensitization immunologic injury
Level of evidence is 5
Mohammed Sobair
3 years ago
What is the take-home message addressed by this article?
Survival advantage for patients undergoing desensitization followed by live donor
transplantation compared with those waiting for a compatible organ offer.
Treatments remove circulating antibody or temporarily inhibit antibody production
without significant effect on immunologic memory. As such, there is a well-
documented memory immune response following HLA-incompatible transplant, with
post desensitization AMR rates generally ranging from 25% to 50%.
Aggressive posttransplant antibody monitoring to identify those patients at higher
risk for rejection and graft loss.
Best option would be to avoid HLA-incompatible transplant whenever possible,
although not necessarily at the expense of significantly prolonged dialysis exposure
while awaiting a compatible offer.
Desensitization its reasonable consideration for those highly sensitized patients
without living donors, where paired exchange is not possible and expected wait
time is considered unacceptable.
The risk/ benefit assessment of desensitization must be reconsidered
Desensitizing treatments are expensive, resource intensive, and place patients at
risk for morbidity associated with potent immunosuppression.
What is the level of evidence provided by this article?
Level of evidence V.
Zahid Nabi
3 years ago
Plasamapheresis PP:
Removing DSAs from circulation. It’s non specific for antibodies removal, all plasma proteins are removed including clotting factors.
The removal of DSAs is short lived with DSAs rebounding to pre treatment level following reequlibration between intravascular and interstitial compartments.
It dose not affect ongoing DSAs production by plasma cells hence its poor choice for desensitization as sole therapy.
It’s side effects include coagulopathy,hypocalcemia, thrombocytopenia,hypotension and catheter related infection.
Therefore IVIg was added to PP.
Intravenous immunoglobuline IVIg derived from gamma globular fraction of plasma from pooled donors.
Its mode of action include:
Inhibit T and B cell proliferation
Inhibit cytokine production.
Inhibit complement activation
Inhibit maturation of dendritic cells.
Induce B_cells apposite.
The protocol for combination of IVIg and PP divided into 2 approaches
1. alternate day PP (no. Of sessions depend on titer of DSAs ) combined with low dose IVIg( 100 mg/kg).
2.PP alternating days with high dose IVIg (1_2 gm/kg).
Low dose IVIg with PP:
AMR , has been reported to be as high as 36%, with 100 % one year graft survival.
This protocol was modified to improve the high risk of AMR ,with the inclusion of ATG for induction,along with Rituximab and splenectomy. Despite that modification, AMR was still high with 43% and graft survival of 78% at 15 months. Same incidence risk was reported with a median follow up of 22 months.
Bortezomib: It is a proteasome inhibitor causing apoptosis of plasma cells. Its use saw transplant of 43% of sensitized patients with 12.5% developing de novo DSAs and 18.8% acute rejection.
Eculizumab: It is an antibody blocking cleavage of C5. If used in addition to IVIG and plasmapheresis, has shown risk of AMR in range of 7.7% to 11.8% as compared to 21.6% to 41.2% seen with IVIG and plasmapheresis, but with an increased risk of invasive infections.
Tocilizumab: It is an antibody against IL-2 receptor which, when used with IVIG in patients unresponsive to IVIG and rituximab, showed good results post-transplant with no AMR at 6 months and good graft function at 1 year post-transplant.
IgG degrading enzyme derived from Streptococcus pyogenes (IdeS): It causes proteolysis at Fc region of IgG. Its use has been shown to be associated with approximately 40% AMR which were treated. Long term effects including infections and malignancies need to be evaluated.
Benefits of desensitization:
Increases sensitized patients access to transplantation by decreasing cPRA & the number of unacceptable antigens for listing.
Patients with a cPRA of > 99.9% have the greatest need for desensitization.
Patients with a cPRA < 98% with an incompatible living donor or those on the waiting list for several years may also benefit from desensitization.
Decreases DSA prior transplantation in patients with positive XM to reduce the risk of immediate graft loss from hyperacute rejection.
Long-term risks of desensitization:
Difficult to determine because most of the studies that looked into this issue were short term.
Overall immunosuppression raises concerns of infections & malignancies.
Reduced survival, mostly related to infections, also reported.
Cost-effectiveness of desensitization:
Desensitization should be reserved for only those patients where all other possible options
are exhausted , it is a costly affair but is worth if used appropriately.
Radwa Ellisy
3 years ago
Take-home messages:
-For those highly sensitized patients:
With a living donor, if failed paired or unavailable kidney program, desensitization is an available option rather than being on dialysis or being on the waiting list for a deceased donor.
Without living donor: Prioritization by specific allocation system KAS decreased from >19 ys to 3.2 years increased the rate of deceased donors for some sensitized patients
– Data favoring desensitization plus living donor than being on the waiting list, as regards patient and graft survival, however this data before the PKD program.
– Desensitization protocols are associated with risk of potent immunosuppression (i.e. infection and malignancy), more acute rejection episodes (25-50%) due to persistent DSAs or de novo DSAs however comparable graft survival, more transplant glomerulopathy, subclinical ABMR
*level 5 (commentary article)
Last edited 3 years ago by Radwa Ellisy
Heba Wagdy
3 years ago
What is the take-home message addressed by this article?
Desensitization treatment remove circulating antibodies and temporarily inhibit antibody production without affecting immunologic memory
It is expensive and increases the risk of morbidity due to potent immunosuppression.
It is better to avoid HLA incompatible transplant with consideration of the adverse effects of prolonged dialysis exposure
Paired exchange donation to avoid the risk associated with desensitization
Highly sensitized patients may proceed with desensitization to avoid unacceptable long waiting time.
Careful selection of patients according to health status and anti-HLA antibody status
What is the level of evidence provided by this article?
Level 5
Innocent lule segamwenge
3 years ago
Desensitization in Kidney Transplant: A Risky (but Necessary?) Endeavor for Those With Limited Options
What is the take-home message addressed by this article?
This paper is an editorial to a paper by Vo et al.
Access to transplantation has improved for highly sensitized patients due to;
1. Changes made in the kidney allocation system
2. National kidney paired exchange
This has shortened waiting time for highly sensitized patients from 19 to 3.2 years.
Has also reduced interest in desensitizing highly sensitized patients.
Drawbacks for desensitization measures; expensive, side effects, immunological memory persist, high rates of AMR post-desensitization.
Findings from a study by Vo et al are highlighted in this editorial.
A cohort study which looked at the post-desensitization immune response of 90 sensitized patients using IVIG, rituximab, +/−PLEX/tocilizumab.
High AMR rates in patients with antibodies pre or post-transplant.
Findings favoured desensitization in highly sensitized patients.
Other centres have not replicated these findings.
A study from Mayo clinic is highlighted which found transplant glomerulopathy in 55% undergoing desensitization compared to 7% in HLA compatible.
The author concludes by not recommending desensitization unless when faced with the choice of patients staying too long on the waiting transplant list.
What is the level of evidence provided by this article?
This is level 4 evidence
Weam Elnazer
3 years ago
Patients who are highly sensitized to allergens may benefit from desensitization, and the effectiveness of these programs is dependent on intensive post-transplant antibody surveillance to identify those patients who are at greater risk for rejection and graft loss, according to the findings.
If live donors are available, the matched exchange should be tried in order to avoid the costs and risks associated with desensitizing treatment, as well as the immunological response that will most likely result in inferior long-term graft survival after the transplant.
Because desensitization can still facilitate early better graft out com compared to haemodialysis, we can accept the desensitization option for those highly sensitized patients without living donors in situations where the paired exchange is not possible and the expected wait time is considered unacceptable. However, close post-transplant DSA monitoring is required to identify patients at risk for rejection and graft loss.
The use of national matched exchange programs is the greatest choice for patients who have live donors who are incompatible with their ABO or HLA.
These developments reduce the waiting time and desensitization protocols, which are expensive, resource-intensive, and associated with a risk of immunosuppression.
Level 5
Hinda Hassan
3 years ago
based on this article, will you accept performing desensitisation of highly sensitised transplantation after running out of all options? Any survival advantage (graft and patient)? Yes I would accept doing desensitisation if there is no chance for paired exchange or no chance for KAS . Despite the worse clinical outcomes and the high costs compared to regular transplantion , desnsetization versus being on dialysis treatment provide a better survival . At 3 years, the transplanted patients had a 14.7–17.6% greater probability of survival than those remaining on dialysis (1). 2 year patient survival was 95% and graft survival was 86% in 725 patients with DSAs who had kidney transplantation with different protocols , but the acute rejection rate was 36% and acute AMR rate was 28%. Studies showed that AMR rates range between was 43% (15 months ) , 39% ( 22 months ) and 33% ( 2 years). Graft survival range was found between 78% ( 15 months),89% ( 22 months) and 93% (at 2 years) One study in 211 kidney recipients compared desensitization in living donation with dialysis or HLA-compatible transplantation over 8 years . Patient survival was : for desensitized group versus dialysis-only group versus dialysis-or-transplantation group were as follows: 90.6%:91.1%:93.1%, at 1 year, 85.7%:67.2%:77.0% at 3 years, 80.6%:51.5% : 65.6% at 5 years and 80.6%:30.5%:49.1% at 8 years (2) 1.Stanley C. Jordan, Jua Choi, Ashley Vo, Kidney transplantation in highly sensitized patients, British Medical Bulletin, Volume 114, Issue 1, June 2015, Pages 113–125, https://doi.org/10.1093/bmb/ldv013 2.Kuppachi, S. and Axelrod, D.A. (2020), Desensitization strategies: is it worth it?. Transpl Int, 33: 251-259. https://doi.org/10.1111/tri.13532
MICHAEL Farag
3 years ago
the evidence is V
home message
============
Desensitization is expensive and carries a high risk of comorbidities and mortality; moreover, no guarantee that rejection will not occur
Given these data, the best option would be to avoid HLA-incompatible transplant whenever possible, although not necessarily at the expense of significantly prolonged dialysis exposure while awaiting a compatible offer.
When living donors are available, the paired exchange should be attempted in order to avoid the cost and risk associated with desensitizing therapy as well as the posttransplant immune response that will likely translate into poorer long-term graft survival.
Hinda Hassan
3 years ago
What is the take-home message addressed by this article?
Patients who are highly sensitized, desensitization with consideration of DSA state can provide them a chance for deceased kidney donation. The risk of AMR is still high approaching 45%. So it is not recommended if there is a chance for either of paired exchange donation or immediate KAS allocation
What is the level of evidence provided by this article?
This is a cohort study .so the level of evidence is 2b The article is an expert opinion so the level of evidence is 5
Ala Ali
Admin
3 years ago
Dear all, please realize that this is a Commentary manuscript on an original work of : Vo AA, Aubert O, Haas M, Huang E, Zhang X, Choi J, Peng A, Najjar R, Sethi S, Ammerman N, Lim K, Jordan SC. Clinical Relevance of Posttransplant DSAs in Patients Receiving Desensitization for HLA-incompatible Kidney Transplantation. Transplantation. 2019 Dec;103(12):2666-2674. DOI: 10.1097/TP.0000000000002691.
Before embarking on DES, paired exchange options should be exhausted, and a realistic estimate of wait time taking into account priorities for high cPRA patients under KAS should be considered.
Once you decide on DES, keep the short and long-term patients outcomes.
II. Desensitization in Kidney Transplant: A Risky (but Necessary?) Endeavor for Those with Limited Options What is the take-home message addressed by this article?
1. Recent changes to the KAS, which prioritized organ offers for highly sensitized patients (cPRA=98%–100%), reduced median waiting time from >19 years to 3.2 years. This & similar concepts in Europe, based on acceptable mismatches, allowed successful transplantation for >1000 patients with excellent outcomes. 2. The increased use of national paired exchange programs allowed more patients, with either ABO or HLA-incompatible living donors, to be transplanted.
3. These developments reduced the interest in desensitization of highly sensitized patients.
4. Limitations to published multicenter data that suggest a survival advantage for patients undergoing desensitization followed by live donor transplantation include:
– These data were collected before implementation of KAS – Control groups were not enrolled in paired exchange programs. Desensitizing is expensive & resource demanding – Morbidity associated with potent immunosuppression. – Desensitizing treatments don’t address immunologic memory; they merely remove circulating antibodies or temporarily halt their production. – High rates of post-desensitization AMR (25%-50%) 5. In a cohort of 90 highly sensitized patients undergoing desensitization, Vo et al concluded that highly sensitized patients may benefit from desensitization & that the success of these programs depends on aggressive posttransplant antibody monitoring to identify those patients at higher risk for rejection & graft loss: – this cohort was largely of deceased donor transplant, unlike the work by Orandi et al which showed survival benefit of desensitization before living donor transplant. – Desensitization in deceased donor transplant wouldn’t predict transplant events. -despite these challenges,Vo et al reported favorable results & acceptable post-transplant outcomes in desensitized deceased donor transplantations. -other centers, however, failed to replicate these encouraging results using similar strategies. 6. A 5-year data from the Mayo Clinic showed worse patient & graft survival as well as TG (by protocol biopsy) in patients undergoing desensitization versus HLA-compatible transplant. 7. From the above data, the best options would be: 1.To avoid HLA-incompatible transplant whenever possible, but not at the expense of very prolonged dialysis exposure while waiting a compatible offer. 2.To attempt paired exchange whenever living donors are available. 3.To reconsider the risk/benefit of desensitization 4,To opt for desensitization only in highly sensitized patients without living donors, where paired exchange is not feasible & would likely unacceptably prolong wait time. What is the level of evidence provided by this article? Level V: Commentary article
Amit Sharma
3 years ago
Desensitization in Kidney Transplant: A Risky (but Necessary?) Endeavor for Those with Limited Options
What is the take-home message addressed by this article?
Highly sensitized patients undergoing desensitization for transplantation have been shown to be having survival advantage as compared to remaining on wait-list. The advent of kidney allocation system and paired exchange programs have increased chances of such patients receiving a compatible kidney, thereby having a positive impact on the graft survival.
Whenever possible, sensitized patients should be entered in a paired kidney exchange program. But it may not be possible in all scenarios. Hence in a highly sensitized patient without a living donor, not eligible for paired exchange program, and expecting an unacceptably long wait-period, it is prudent to desensitize the patient for transplant and keep a close follow-up post-transplant using DSA monitoring and protocol biopsies.
What is the level of evidence provided by this article?
Level 5: Expert commentary
Zahid Nabi
3 years ago
Yes I would go for desensitization in such a scenario.
Graft and patient survival is different for deceased and living donor transplant.
Mayo Clinic showed significantly worse patient and graft survival in those undergoing desensitization versus HLA compatible transplant.
Protocol biopsies detected TG in 55% of desensitized versus 7% of HLA compatible recipients.
Ideally HLA incompatible transplant should be avoided however not necessarily at expense of prolong dialysis exposure.
Paired exchange is better option if possible.
Abdulrahman Ishag
3 years ago
What is the take-home message addressed by this article?
1- Desensitizing treatments are expensive, resource intensive, and place patients at risk for morbidity associated with potent immunosuppression.
2- Desensitization treatments remove circulating antibody or temporarily inhibit antibody production without significant effect on immunologic memory.
3- highly sensitized patients may benefit from desensitization and that the success of these programs relies on aggressive post transplant antibody monitoring to identify those patients at higher risk for rejection and graft loss.
5- When living donors are available, paired exchange should be attempted in order to avoid the cost and risk associated with desensitizing therapy as well as the post transplant immune response that will likely translate into poorer long-term graft survival.
6- proceeding with desensitization for those highly sensitized patients without living donors, where paired exchange is not possible and expected wait time is considered unacceptable, may be a reasonable consideration.
What is the level of evidence provided by this article?
Level 5
Transplantation is the best option for ESRD patients on dialysis ,highly sensitized recipients have limited options for transplantation.
kidney allocation system (KAS) and paired exchange programs have improved transplantation in sensitized patients ,decreased waiting time on dialysis and decreased the need for desensitization.
Although desensitization can be a rescue solution for very highly sensitized recipients ,but still there is many disadvantages.
*Desensitizing treatments are expensive, resource intensive.
* place patients at risk for morbidity associated with potent immunosuppression.
*It removes circulating antibody or temporarily inhibit antibody production without signifcant effect on memory cells with AMR rates generally ranging from 25% to 50%.
*5-year data from the Mayo Clinic showed worse patient and graft survival in those undergoing desensitization versus HLA-compatible transplant, as well as protocol biopsy-detected transplant glomerulopathy in 55% of desensitized versus 7% of HLA-compatible recipients.
*so the best option would be to avoid HLA-incompatible transplant whenever possible ,use paired exchange programme with living donor is better than desensitization.
*desensitization of highly sensitized patients with living donors, where paired exchange is not possible and expected wait time is considered unacceptable, may be a reasonable consideration.
*desensitization is centre based experience and no fixed protocol.
*Desensitization remains a good way to access transplantation for highly sensitized recipients when there is no other available options and still better option than waiting on dialysis.
*Close follow up of DSA and protocol biopsy of desensitization transplanted patients with early detection of subclinical AMR with early treatment may help to improve graft outcome and patient survival.
Jamila Elamouri
3 years ago
desensitization in Kidney Transplant: A Risky (but Necessary?) Endeavor for Those with Limited Options
Level 2 evidence
Take-home messages:
Desensitization is a way to make transplantation accessible for highly sensitized recipients. • It gives good chance than long waiting on hemodialysis for the patient. nevertheless; it should only be carried out if there is no other option like Paired kidney donation. • It just removes the DSA temporally and has no effect on the memory cells which can trigger an immune reaction to the allograft causing AMR and ultimately graft failure. About 55% of the desensitized recipient developed transplant glomerulopathy on protocol biopsy as compared to 7% of HLA-compatible recipients. • Desensitized patients need more aggressive follow-up with DSA monitoring and protocol biopsy, which will increase the cost of already costly procedure • There is no universal protocol for desensitization. it is centre experience-dependent and this makes a difference in outcome; so we can not generalize the results. • It carries multiple risks to the patients like infection and malignancy, so need to select patients carefully.
Mohamed Saad
3 years ago
Desensitization in Kidney Transplant: A Risky (but Necessary?) Endeavor for Those With Limited Options.
The home message:
1-Try to avoid HLA in-compatible transplantation as much as we can.
2-When living donors are available, paired exchange should be attempted in order to avoid the cost and risk associated with desensitizing therapy.
3-If paired exchange not available and the patient is highly sensitized and on waiting list for long time with an incompatible live donor option, desensitization should be considered and outweigh the risk/ benefit ratio .
4-Desensitized patients is high risk for AMR post kidney transplant so should be strictly followed by DSA and kidney biopsy. Level of evidence is 2 B
Dear Dr Mohamed
It can not be level 2 B
IT IS LEVEL 5…..It is expert opinion (level 5)
amiri elaf
3 years ago
# What is the take-home message addressed by this article?
#The development of the following options improved renal transplantation in highly sensitized patients:
# Change to the kidney allocation system (KAS) for highly sensitized patients with high levels of DSA (cPRA of 98%–100%).
– organ allocation to sensitized patients based on acceptable mismatches has successful transplantation with excellent long term outcomes.
# Use of national paired exchange programs best option for patients with either ABO or HLA incompatible living donors.
# As a result of these developments it decrease the waiting time and desensitization protocol which are expensive, resource intensive, risk of immunosuppression and these treatments remove circulating antibody or temporarily inhibit antibody production without significant effect on immunologic memory.
# Patients may benefit from desensitization with post transplant DSA monitoring to identify risk for rejection and graft loss.
# Thus we can accept the desensitization option for those highly sensitized patients without living donors, where paired exchange is not possible and expected wait time is
considered unacceptable, because desensitization is still facilitate early better graft out com compared to heamodialysis
but we need close post transplant DSA monitoring to identify risk for rejection and graft loss.
# What is the level of evidence provided by this article?
# Level 2
The article is like editorial comment so evidence is level 4
The take-home message is that we should not consider desensitization as the first option in very high sensitized patients as desensitization has little to do with memory cells. son late or chronic rejection is still a challenge. donor exchange is preferable. My opinion is with desensitization if this is the only chance after explaining to donor and recepient
Alaa eddin salamah
3 years ago
Desensitization in Kidney Transplant: A Risky (but Necessary?) Endeavor for Those with Limited Options
Take home messages
1- Avoid HLA-incompatible transplant when possible
2- Paired exchange program is a favorable option for highly sensitized patients which will decrease the costs, risks and post-transplant immune response of desensitization which lead to poor graft outcome
3- Desensitization is an option if paired exchange program is not feasible and there is expected long waiting time
The level of evidence is IIb (individual cohort study)
Article Summery:
Highly sensitized patients had two important breakthroughs to improve their chance of transplantation:
1- Kidney allocation system (KAS) which prioritized organ offers for patients with high Anti HLA Abs with cPRA 98-100% which decreased median waiting time from >19 yrs to 3.2 yrs.
2- The use of national paired exchange program.
Desensitizing treatments are expensive, resource intensive, and place patients at risk for morbidity associated with potent immunosuppression also these treatments remove circulating antibody or temporarily inhibit antibody production without significant effect on immunologic memory leading to Post desensitization AMR which range from 25-50%.
Vo et al studied post desensitization immune response in a cohort of highly sensitized 90 patients underwent desensitization with IVIG, Rituximab +/-PLEX/Tocilizumab with mostly deceased donor transplant and concluded that highly sensitized patients may benefit from desensitization with favorable graft outcome and that the success of these programs relies on aggressive posttransplant antibody monitoring to identify those patient at higher risk for rejection and graft loss other centers have failed to replicate these encouraging results using similar strategies like Mayo Clinic experience.
In Vo et al study Despite aggressive posttransplant DSA monitoring in the current report by Vo et al, histologically idented AMR was detected in 29% of desensitized recipients. And this was associated with significant risk of graft glomerulopathy and failure (this is a limitation of the Vo et al study, because the median follow up period was 2.9 yrs, which may not be enough to detect these worse graft outcomes).
Not sure about the level of evidence of the study.
Ban Mezher
3 years ago
Level of evidence is 2
Home messages:
When it is possible it is better to avoid HLA incompatible transplantation but not on expense of prolonged dialysis time.
if living donor is available but incompatible, it is better to attempt paired exchange to reduce desensitization cost & its complications
when paired exchange is not feasible, desensitization can be considered inspire of its cost.
If highly sensitized patient had no chance for living donor & exchange program, I will use desensitization for him because it will improve both graft & patient survival.
– The kidney allocation system (KAS) and national paired exchange programs facilitate transplants in highly sensitized patients, reduce waiting time for transplantation and decrease the need for desensitization.
-National paired exchange programs are the best options for patients with either ABO or HLA-incompatible living donors.
– KAS increases rates of deceased donor transplants but not all highly sensitized patients. Desensitization is recommended for:
· highly sensitized patients without living donors and long waiting time
· If a paired exchange is not possible for the patient.
-Desensitizing treatments are expensive, resource-intensive, and place patients
at risk for morbidity associated with potent immunosuppression.
-Desensitization remove circulating antibody or temporarily inhibit antibody production without significant effect on immunologic memory which may be associated with AMR.
-Highly sensitized patients may benefit from desensitization and they need aggressive posttransplant DSA monitoring.
-Desensitization is associated with transplant glomerulopathy , AMR and graft failure.
–Avoidance of HLA-incompatible transplant whenever possible. -Level of evidence :2b
☆Desensitization in Kidney Transplant: A Risky(but Necessary?) Endeavor for Those With Limited Options
♧Home messages:
Desensitizing treatments:
____________________________
▪︎ Are expensive, resource intensive, and place patients at risk for morbidity ass with potent immunosuppression.
▪︎Remove circulating antibody or temporarily inhibit antibody production without significant effect on immunologic memory (there is a well-documented memory immune response following HLA-incompatible transplant, with post desensitization (AMR))
▪︎Conducted by IVIG, rituximab, +/-PLEX/tocilizumab, and stratified by DSA status at the time of and following transplant.
▪︎Give benefits to highly sensitized patients and the success of these programs relies on aggressive post-transplant antibody monitoring to identify those patients at higher risk for rejection and graft loss.
▪︎Some studies shows worse patient and graft survival in those undergoing desensitization versus HLA compatible transplant, as well as protocol biopsy-detected transplant glomerulopathy in desensitized pts.
Important points:
___________________
▪︎Avoid HLA-incompatible transplant whenever possible.
▪︎Paired exchange is superior to desensitization when living donors are available (but paired exchange is not a feasible option for most highly sensitized recipients).
▪︎ The risk/ benefit assessment of desensitization must be reconsidered.
▪︎ Proceeding with desensitization for those highly sensitized patients without living donors may be a reasonable consideration.
▪︎Variability in desensitization is influenced by many factors:
1. Specific desensitization regimen.
2. The cross-match assay(s) utilized.
3. The level of cross-match reactivity that
a given center considers “acceptable.”
▪︎ Careful selection of patients for desensitizing treatment is mandatory to avoid serious harm
▪︎ If desensitization is considered for highly sensitized patients, expectations should be tempered. Paired exchange options should be exhausted, and a realistic estimate of
wait time taking into account priorities for high cPRA patients.
Take home message is that,desensitization program for highly sensitized patients is not the perfect solution. For several reasons,as follows:
2 important developments have significantly improved access to transplant for highly sensitized patients (defined as cPRA of 98%_100%):
1st is change to kidney allocation system KAS,prioritized organ offers for highly sensitized patient. Wait time reduced from 19 years to3.2 years. Based on acceptable mismatches.
2nd is the increased use of national paired exchange program HLA highly sensitized patients with HLA_incompatible living donors.
Desensitization treatment: draw backs
1)Expensive,resource intensive with high morbidity associated with potent immunosuppressive.
2)Technically Desensitization treatment remove circulating antibodies or temporarily inhibit antibody production without significant effect on immunologic memory. AMR risk post Desensitization is generally 25 to 50 %.
Vo et al study revealed high rate of AMR post desensitization, in patients with persistent pretransplant and post transplant DSA (45%), and (70%) of patients who developed De novo DSAs but were negative at transplant time.Risk of developing De novo is 25%.
Furthermore 5_year Data from Myo Clinic revealed transplant glomerulopathy 55% of desensitized vs7% of HLA compatible recipients.
Therefor desensitization treatment is to be avoided ,but in few patients who failed to be managed by the protocols mentioned earlier.
It’s level II evidence based study
Over the last 2 decades, 2 developments have improved access to kidney transplantations for highly sensitized patients. First, a change to the kidney allocation system which gave recipients access to transplantation regardless of sensitization status. Second is the use of national paired exchange programs such as the National Kidney Registry, for better matching for ABO or HLA-incompatible living donors.
As a result of these developments, desensitization of highly sensitized patients has decreased.
Desensitizing treatments are associated with increased risk of post-transplant infections and malignancy, along with expenses. These treatments aim to remove circulating antibody or temporarily inhibit antibody production without significant effect on memory cells.
The provided article support the transplant of highly sensitized recipients regardless of the origin of the donor kidney. However, it is better to avoid HLA-incompatible transplant whenever possible.
When living donors are available, paired exchange should be attempted before the decision to proceed with transplantation especially if desensitization is recommended.
Sensitized patients are still at risk of acute antibody mediated rejection due to preformed or de novo DSA even following aggressive desensitization treatment. Desensitization treatment is more effective when living donor is selected.
Posttransplant outcomes in desensitized patients receiving deceased donor transplants are better comparing to patients on the waiting list. But in this particular group, posttransplant protocol biopsies and monitoring of immunosuppression serum levels are crucial to detect early and subclinical rejections.
What is the level of evidence provided by this article
MOHAMMED GAFAR medi913911@gmail.com
3 years ago
Desentiztion protococls for tretament for highly senstized patients are expensive, and resuorce intensive and puts the ptient at risk of morbidity assicioted with potenet immunosuprresion.
These treatments remove circulating antibody or temporarily inhibit antibody production without significant effect on immunologic memory.
There is a well-documented memory immune response following HLA-incompatible transplant, with postdesensitization antibody-mediated rejection (AMR) rates generally ranging from 25% to 50% .
HLA incomaptible transplantion should be avoided .
Paired exchange programm should be enocuarged for living non comaptible donors .
Kidney allocation system for cadveric donors (KAS) in USA has decreaesd the waiting time for highly sensitized patients from 19 years to 3.2 years and should be apllied in each country.
LEVEL OF EVIDENCE 2
Abdul Rahim Khan
3 years ago
In highly sensitized patients the best options would be – paired kidney donation and exchange in case of living donor and kidney allocation system for deceased donor. If paired exchange is not available and there is long waiting list then desensitization protocol can be considered.
Non compatible transplantation should be avoided as –
-There is risk of infection and malignancy and desensitization is only transient process and rebound effect may induce worse rejection.
– The desensitization protocols are costly
-Overall outcome are worse with TG and AMR
-Desensitisation outcome can variable between transplant centres and will depend on method of selection of patients, drug protocols, and close monitoring post transplant
What is the level of evidence provided by this article
Doaa Elwasly
3 years ago
-Take home message
AMR rates are increased in patients with persistent DSA and with de novo DSA
Desensitization can be a successful option for highly sensitized cases but needs close monitoring of DSA to detect early rejection liability .
Paired kidney exchange programs is another option to avoid risk and cost burden associated with desensitization treatment, as desensitization risk versus benefit outcomes need to be evaluated for each case .
Paired kidney exchange should be considered for patients with high c PRA , considering the waiting time for prioritizing such cases .
-Level of evidence II
Sahar elkharraz
3 years ago
Highly sensitised patients have high risk of transplant loss despite using desensitisation protocol because temporary inhibition of antibodies production and with long term may develops de novo DSA which lead to loss of graft also high dose of immunosuppressive drug are very expensive and may expose patients to serious opportunistic infection and side effects of drug.
So highly sensitised patients better to avoid transplant and locking for another option like Kidney allocation system help to increase rate of deceased donor transplant or
Shift patients to Parried donor exchange program which facilitates transplant of patients with ABO and HLA incompatible with others compatible.
But if there’s no option to high sensitised patients better do transplant with high dose of desensitisation immunosuppressive drug with extensive monitoring for DSA level and biopsy protocol because high risk of transplant glomerulopathy
Finally transplant better than patients become for long time on dialysis.
Q2: Evidence II cohort study
Filipe prohaska Batista
3 years ago
What is the take-home message addressed by this article?
Although desensitization of patients undergoing kidney transplantation is an option that has considerably reduced the waiting time in a specific group of patients sensitized over the years for various reasons (pregnancy, blood transfusion, vaccination, viral diseases, previous transplantation).
Highly sensitized patients should prioritize compatible living donors and only when they are not available to follow the Kidney Allocation System (KAS) deceased donor protocol.
When the waiting period for an organ becomes unacceptable, the patient should be desensitized and proceed to transplantation.
However, the patient must be informed of the risks involved and the need for a high-cost treatment, risks of infection due to prolonged important immunosuppression, and more aggressive monitoring with DSA protocols and biopsies.
The individualization of the follow-up of each patient is essential in choosing both the sensitization protocol and the maintenance immunosuppression to be performed.
What is the level of evidence provided by this article?
Prospective cohort (level 2b evidence).
Ibrahim Omar
3 years ago
What is the take-home message addressed by this article?
kidney transplantation in highly sensitized patients remains a significant problem in most transplantation centers as they need desensitization protocols that are expensive and include potent immunosuppression that has a serious morbidity.
to improve access to transplant for highly sensitized patients, there are 2 main successful systems that contribute to decreased desensitization use. these systems are :
1- kidney allocation system (KAS) that prioritized organ offers for these patients.
2- national exchange paired program.
however, the best option is still to avoid HLA-incompatible transplant whenever possible but not on the expense of increasing dialysis exposure and waiting times.
proceeding with desensitization for highly sensitized patients when paired exchange is not possible, may be a reasonable consideration as there are some published encouraging results regarding the effect of desensitization on graft function and survival.
What is the level of evidence provided by this article?
the level of evidence is II
fakhriya Alalawi
3 years ago
· Desensitizing treatments are expensive, resource-intensive, and place patients at risk for morbidity associated with potent immunosuppression.
· Highly sensitized patients may benefit from desensitization and the success of these programs relies on aggressive post-transplant antibody monitoring to identify those patients at higher risk for rejection and graft loss as in Vo et al analysis
· When living donors are available, the paired exchange should be attempted in order to avoid the cost and risk associated with desensitizing therapy as well as the post-transplant immune response that will likely translate into poorer long-term graft survival.
level 2
Batool Butt
3 years ago
Take home message
National paired kidney donation and exchange in case of living donor and Kidney allocation system (KAS) for the deceased donor are the best options for transplantation in highly sensitized recipients (HLA and ABO-incompatible). Desensitization protocol can be the option only if the patient is highly sensitized and no living donor or paired exchange is available and waiting list time is unacceptable. Desensitization has a transient effect and cannot affect memory cells, which can induce more potent AMR, transplant glomerulopathy , and worse long-term patient and graft survival. According to the Mayo Clinic data, transplant glomerulopathy occurs in more than 55% of desensitized patients in five years when compared to HLA-compatible recipients (7%). Desensitization protocols are expensive and increase the chances of infection and malignancy and also their results vary between centers due to different desensitization regimens used, proper selection of recipient who can tolerate the strong immunosuppressive therapy without adverse consequences, method of XM and the level of cross-match reactivity that is acceptable in a particular center. The best option is to avoid HLA-incompatible transplantation whenever possible, but if desensitization needed, then close monitoring of DSA all through the transplantation follow up period is needed.
LEVEL OF EVIDENCE: 2
AHMED Aref
3 years ago
What is the take-home message addressed by this article?
The article addressed these points:
Ø Desensitization is a risky approach as it may be associated with many complications. Moreover, the effect of removal of the DSA is usually temporary due to the persistence of the memory immune response.
Ø Desensitized recipients still have a lower allograft survival than those who received a compatible allograft.
Ø The priority given by different allocation systems to highly sensitized recipients on the waiting list has dramatically improved the waiting time for such patients. Therefore, the desensitization option became less attractive than before.
Ø Paired kidney donation proved to be the best option for highly sensitized patients to obtain the best-matched allograft, provided that the patient has a willing living donor.
What is the level of evidence provided by this article?
Based on this article, will you accept performing desensitisation of highly sensitised transplantation after running out of all options?
Any survival advantage (graft and patient)?
will you accept performing desensitisation of highly sensitised transplantation after running out of all options?
Yes.
Desensitization became less attractive if the patient had a better option (e.g. paired kidney donation). Nevertheless, desensitization may be the only option for a group of highly sensitized recipients who have no alternative options except to continue on dialysis while they are on the waiting list.
Montgomery, et al. 2011. Documented a significant survival advantage for those transplanted after desensitization compared to patients who continued on dialysis (1). The patient survival for recipients of kidney allograft after desensitization was 90.6% at 1 year, 85.7% at 3 years, 80.6% at 5 years, and 80.6% at 8 years, as compared with rates of 91.1%, 67.2%, 51.5%, and 30.5%, respectively, for patients in the dialysis-only group and rates of 93.1%, 77.0%, 65.6%, and 49.1%, respectively, for patients in the dialysis-or-transplantation group (P<0.001 for both comparisons).
References:
1) Montgomery RA, Lonze BE, King KE, et al. Desensitization in HLAincompatible kidney recipients and survival. N Engl J Med 2011; 365: 318.
Thanks Ahmed
yes we can accept the desesitisation therapy in very highly sesensitized candidate as its still assocaited with better early graft and patient survival compared to longwaiting on dialysis but with in 5 years the risk of chronic rejection , Tg and graft loss increased up to 55% in the presence of denovo DSA , that why the frequent DSA s monitoring post transplant and timely treating AMR considered one of the important fcators that can improve thelong term graft survival.
Excellent
If KAS and paired exchange program both failed ,I would accept, as despite higher rate of AMR, all patients experienced similar graft survival with a median follow up time of 2.9 years. However the 5 year graft and patient survival was worse in those undergoing desensitization vs HLA comparable transplants. Despite all the adverse prognosis,I think it’s still better than the prognosis related to regular hemodialysis.
Agree, better than dialysis is failed in the paired exchange scheme
YES, keeping in mind that Desensitization is a last resort taking into account that favorable outcome relies on aggressive posttransplant Abs monitoring and protocol biopsies to identify patients with higher risk of rejection and
Vo AA, Haas M, Huang E, et al. Clinical relevance of post-transplant
donor specific antibodies (DSAs) in patients receiving desensitization
for HLA incompatible kidney transplantation. In press.
after running out of all options, yes we can accept to do desensitization and transplantation after it for better quality of life than staying on dialysis, of course survival of graft will be better than not doing desensitization and the patient survival is better than staying on dialysis, but we should close monitor DSA after transplantation
Based on this article
Yes i would accept to do desensitization as it remains a good way to access transplantation for highly sensitized recipients when there is no other available options and still better option than waiting on dialysis.
*Close follow up of DSA and protocol biopsy of desensitization transplanted patients with early detection of subclinical AMR with early treatment may help to improve graft outcome and patient survival.
*Careful patient selection, which involves the identification of individuals who can withstand desensitization treatment and have favorable antibody profiles amenable to successfully overcoming the incompatibility to allow transplantation, remains the cornerstone desensitization.
*Patients with DSA and T-cell activation as demonstrated by high levels of soluble CD30 (sCD30) in pretransplant serum have a threefold higher risk of graft loss than patients with DSA but low sCD30 levels . Using this and other novel biomarkers to follow treatment response in addition to traditional DSA MFI/titer measurement may offer additional guidance into management before and after transplantation.
Vineeta Kumar and Jayme E. Locke.New Perspectives on Desensitization in the Current Era – An Overview.Front. Immunol., 30 July 2021 |
will you accept performing desensitisation of highly sensitised transplantation after running out of all options?
Yes. In those highly sensitized patients who do not have a living donor, are not eligible for paired exchange program, and have along expected waiting period, desensitization should be performed as data has shown a definite survival advantage.
Any survival advantage (graft and patient)?
Data from US showed a definite advantage of HLA incompatible transplant after desensitization (as compared to remaining on wait-list) with reference to patient survival at 1,3,5 and 8 years with it being as high as 1.75 times more by 8 years post-transplant (76.5% versus 43.9%). (1)
Although, the data from UK shows that there is no survival benefit and the results are comparable in the 2 groups. (2)
Reference:
1) Orandi BJ, Luo X, Massie AB, Garonzik-Wang JM, Lonze BE, Ahmed R, Van Arendonk KJ, Stegall MD, Jordan SC, Oberholzer J, Dunn TB, Ratner LE, Kapur S, Pelletier RP, Roberts JP, Melcher ML, Singh P, Sudan DL, Posner MP, El-Amm JM, Shapiro R, Cooper M, Lipkowitz GS, Rees MA, Marsh CL, Sankari BR, Gerber DA, Nelson PW, Wellen J, Bozorgzadeh A, Gaber AO, Montgomery RA, Segev DL. Survival Benefit with Kidney Transplants from HLA-Incompatible Live Donors. N Engl J Med. 2016 Mar 10;374(10):940-50. doi: 10.1056/NEJMoa1508380. PMID: 26962729; PMCID: PMC4841939.
2) Manook M, Koeser L, Ahmed Z, Robb M, Johnson R, Shaw O, Kessaris N, Dorling A, Mamode N. Post-listing survival for highly sensitised patients on the UK kidney transplant waiting list: a matched cohort analysis. Lancet. 2017 Feb 18;389(10070):727-734. doi: 10.1016/S0140-6736(16)31595-1. Epub 2017 Jan 6. Erratum in: Lancet. 2017 Feb 18;389(10070):700. PMID: 28065559.
proceeding with desensitization for those highly sensitized patients where paired exchange is not possible and expected wait time is considered unacceptable, may be a reasonable consideration. desensitization was found to be associated with better early graft and patient survival compared to longwaiting on dialysis .
If it is the only option , I can accept desensitization as QOL will be better than long stay on dialysis, but with caution regard:
_ close and regular follow up of DSA to detect ant rejection episodes early.
_ use protocol biopsy to detect subclinical rejection.
_ screening for malignancy which increase in the context of highly suppressive therapy .
Inspite of high rates of AMRs & TG, I will strike a balance & proceed to desensitization only in highly sensitized patients without living donors, where paired exchange is not feasible & would likely unacceptably prolong wait time.
yes, After exhausting all other options, we decided that doing desensitization and transplantation afterwards would provide a better quality of life than remaining on dialysis. Of course, the graft’s survival will be better than not doing desensitization, and the patient’s survival will be better than remaining on dialysis.
Yes .
There’s survival advantage for patients undergoing desensitization followed by live
donor transplantation compared with those waiting for a compatible organ offer.
I would proceed with desensitization for those highly sensitized patients without living donors, where paired exchange is not possible and expected wait time is considered unacceptable
The survival benefit still better than prolong dialysis but the ABMR or chronic allograft rejection might be between 25-50%. It is still a risk to take, but in my opinion, its a better risk to take than being longer with dialysis.
Yes, it is better than keeping the patient on dialysis, as the survival rate is higher in transplanted patients, but still, the long term patient and graft survival is lower in desensitized patients as compared to HLA-compatible transplant recipients
Sure patient survival is better with transplantation if compare with those patient stay on hemodialysis .
regarding graft survival of high sensitize patient ,although short term (one year )graft survival the same for non sensitized but 5 year graft survival inferior to non sensitized group.
Based on this article, will you accept performing desensitisation of highly sensitised transplantation after running out of all options?
Any survival advantage (graft and patient)?
Yes , I will accept desensitisation as best option in highly sensitised patient after running out of all option ( paired exchange scheme ) instead of being on waiting list for long period or long-term dialysis.
Also associated with better early graft and patient survival than long-term dialysis,but increase risk of chronic rejection, transplant glomerulopathy and graft loss up to 55% due to development of de novo DSA WHICH NAKE FREQUENT MONITORING OF DSA POST-TRANSPLANT IS NECESSARY .
yes sir
in spite of being highly sensitized patient has higher rate of ABMR (ABOUT 30%) with lower patient and graft survival, the outcome is more worse by remaining on HD PROGRAM.
The original article by Vo et al is an observative prospective study for which the level of evidence of 2…The above is an expert commentary on the same, so the level of evidence becomes 5
The article highlights the importance of desensitization in kidney transplants in the
United States…Over the past 2 decades the kidney transplant patients rates have improved because of the Kidney Allocation system where in the wait list of the recipients in the US have been given points and 4 points are awarded if their cPRA >80%. This improved the waiting time of those highly sensitized patients from 19 years to 3.2 years…The second development was the development of National Registry for paired kidney exchange program which has facilitated the kidney transplant for patients without desensitization…These 2 programs have lead to the overall decline in the rate of desensitization program…Nevertheless desensitization program allows the transplant of patients who are on the waiting list for a long time and do not get a kidney. Infact the survival rate of HLAi Renal transplant after desensitization is better than waiting on the hemodialysis waiting list at 1 year, 2 years and 5 years…
In this study they have described a cohort of 90 patients who are highly sensitized, who underwent pre transplant aggressive desensitization protocols and followed them later…the conclusion was that highly sensitized patients may develop AMR in the post operative period as de novo DSA develop in these individuals and AMR can develop later in them…But they have reported comparable short term benefit among the sensitized and the non sensitized patient groups….But other data are not similar..Data from Mayo clinic show worst transplant outcomes in terms of more transplant glomerulopathy and AMR in HLAi Transplant…The limitation of the study by Vo et al was that all were limited to deceased donor renal transplants only…
In general, the take home message would be that transplant for highly sensitized renal transplant patient should have an individualized approach…the risks of mortality waiting on hemodialysis should be weighed against transplant with anti HLA antibodies…The first option should be HLA compatible donor. If not available, transplants should be counselled for ABOi renal transplants. Kidney Allocation systems are not well developed in many developing countries, hence HLAi renal transplants may still be a better bet in these group of patients…Paired kidney exchange program also offers a better advantage when compared to desensitization but the waiting time should not get prolonged for more than 2 to 4 years when the mortality rates of dialysis takes over…
It is better to avoid desensitization due to its hazards ( over-immunosuppression ,infection malignancy , high cost ) if the patient has alternative option as kidney paired donation.But, if the patient has no other option , proceed to kidney transplant with desensitization some study show a survival advantage for patients undergoing desensitization followed by live donor transplantation compared with those waiting for a compatible organ offer, and still on dialysis.
highly sensitized patients may bene!t from desensitization and that the success of these programs relies on aggressive posttransplant antibody monitoring to identify those patients at higher risk for rejection and graft loss.
Desensitization in Kidney Transplant: A Risky (but Necessary?) Endeavor for Those with Limited Options.
This is a narrative review with level 5 evidence for the clinical approach for transplantation among highly sensitized recipients. First enrol highly sensitized recipients into pair kidney transplant exchange program. Change for the allocation in the kidney Allocation System ( KAS ) by prioritized organ offers for patients with high levels of anti-HLA sensitization. Change in KAS involve intensive desensitization protocol for highly sensitize recipient. However, we should assess patients and counsel regarding the risks and benefits for continuing renal replacement therapy or proceed with desensitization protocol. Regular DSA monitoring and protocol allograft biopsy should be performed for early detection of graft rejection so that prompt action can be taken. IVIG, rituximab, Plasmapharesis, tocilizumab, stratified by donor-specific antibody (DSA) status at the time of and following transplant.
Based on this article, will you accept performing desensitisation of highly sensitised transplantation after running out of all options?
Any survival advantage (graft and patient)
I would first arranging multidisciplinary counselling session with potential recipient who is highly sensitised. Explain the possible risk for continue long term dialysis and proceed with transplantation in highly sensitized recipient. Financial support for potential recipient should be explore as transplantation among highly sensitive individual involve complicated and expensive desensitization treatment and high risk of allograft rejection.
I would accept performing desensitization if patient has exhausted other compatible kidney pair program. Successful desensitization recipient has a good graft survival. However, risk of AMR post-transplant is estimated 25-50%.
Take home message
Level of evidence
This article is a narrative review. Level of evidence 5.
Desensitizing treatments are expensive, resource intensive, and place patients at risk for morbidity associated with potent immunosuppression.
These treatments remove circulating antibody or temporarily inhibit antibody production without signicant effect on immunologic memory. As such, there is a well-documented memory immune response following HLA-incompatible transplant, with postdesensitization antibody-mediated rejection (AMR) rates generally ranging from 25% to 50%.
Desensitization to facilitate deceased donor transplant is arguably a more challenging hurdle due to the lack of predictable transplant events.
The best option would be to avoid HLA-incompatible transplant whenever possible, although not necessarily at the expense of signicantly prolonged dialysis exposure while awaiting a compatible offer
Due to the kidney allocation system (KAS) and national paired exchange programs such as the National Kidney Registry enthusiasm (and need) for desensitization of highly sensitized patients has decreased in recent years.
2-Desensitiztion in kidney transplant=A risky (but necessary)
What is the take-home message advised by this article?
Highly sensitized patients without living donors where pared exchange is not possible and expected wait time is considered unacceptable so proceeding with desensitization may be reasonable consideration
So those patients at the highest risk of posttransplant immunologic injury following desensitization and emphasizes the importance of careful antibody maintaining throughout the post renal transplant period.
Despite aggressive postrenal transplant DSA monitoring in the current report VO et al, histological identified AMR was detected in 29% of sensitized recipients.
If living donor are available, paired exchange should be considered to avoid cost and risk of desensitization therapy.
2- level of evidence of this article is 5
1- it is important to avoid transplantation of highly sensitized patient ,this can be achieved by
a- kidney allocation system (not available in my country)
b- kidney paired exchange (not available in my country)
by these two system the better compatible (donor-recipient ) can be found
if it is not
desensitization and then transplantation has better patient and graft outcome than remaining on HD program .
although desensitization has its own risk (infection ,malignancy ,hypocalcemia ,coagulopathy) and high cost .
(expert opinion ) level 5
What is the take-home message addressed by this article?
* Highly sensitised patients undergoing desensitisation with living donor if failed pair exchanged than being on waiting list and carrying hazard of long term dialysis.
* Desensitisation treatment may be expensive, resource intensive and place patient at risk for morbidity associated with potent immunosuppression, although this treatment remove circulating antibody or temporarily inhibit antibody production without significant effect on immunological memory.
What is the level of evidence provided by this article?
Level v expert opinion
From this article, we can reflect on the gains that can exist with the risks and gains of desensitizing a patient. The desensitization allows the recipient to receive an organ from a deceased donor with acceptable risks of graft rejection.
This involves higher costs, however it seems to be a final strategy for those patients who, even after the change to the kidney allocation system (KAS) and the increased use of national paired exchange programs, are unable to obtain an organ donation.
There is greater risk for long-term graft loss, but acceptable. More fearful seems to be the increased risk of opportunistic infections for patients.
This is not a study, this is a opinion expert – level evidence 05.
–What is the take-home message addressed by this article?
we should have enthusiasm to establish kidney allocation system (KAS)and national paired exchange program in our country to give access for highly sensitizing patient for transplantation with less cost and short waiting time.
What is the level of evidence provided by this article?
level 5
the take home message is desensetization is an available option for patients who fail to have aliving donor or waiting so long on dialysis .
Desensitization treatments remove circulating antibody or temporarily inhibit antibody production without significant effect on immunologic memory.
also desenstization carry the risk of infection malignancies added to high cost.
kidney allocation system and paired exchange programs have increased chances of such patients receiving a compatible kidney, thereby having a positive impact on the graft survival.
level v
Desensitizing treatments are expensive, resource intensive, and place patients at risk for morbidity associated with potent immunosup- pression. Furthermore, these treatments remove circulating antibody or temporarily inhibit antibody production with- out significant effect on immunologic memory. As such, there is a well-documented memory immune response fol- lowing HLA-incompatible transplant, with postdesensiti- zation antibody-mediated rejection (AMR) rates generally ranging from 25% to 50%.
highly sensitized patients may benefit from desensitization and that the success of these programs relies on aggressive post- transplant antibody monitoring to identify those patients at higher risk for rejection and graft loss.
survival advantage was attributed to desensitization before living- donor transplant.
Vo et al7 have reported favorable results both in achieving transplant as well as acceptable posttransplant outcomes in desensitized patients receiving deceased donor transplants.
Despite aggressive posttransplant DSA monitoring in the current report by Vo et al, histologically identified AMR was detected in 29% of desensitized recipients.
the best option would be to avoid HLA-incompatible transplant whenever possible, although not necessarily at the expense of significantly prolonged dialysis exposure while awaiting a compatible offer.
When living donors are available, paired exchange should be attempted in order to avoid the cost and risk associated with desensitizing therapy as well as the posttransplant immune response that will likely translate into poorer long-term graft survival.
Changes in KAS have helped to increase rates of deceased donor transplant for some but not all highly sensitized patients.11 Thus, proceeding with desensitization for those highly sensitized patients without living donors, where paired exchange is not possible and expected wait time is considered unacceptable, may be a reasonable consideration.
Paired exchange options should be exhausted, and a realistic estimate of wait time taking into account priorities for high cPRA patients under KAS should be considered. With this in mind, the current study by Vo et al provides an important guide for clinicians to identify those patients at the high- est risk of posttransplant immunologic injury following desensitization if one chooses this route and emphasizes the importance of careful antibody monitoring throughout the posttransplant period.
Level 5
What is the take-home message addressed by this article?
-Highly sensitized patients can proceed in transplant after desensitization or paired kidney exchange and transplant better than staying in waiting list.
– Desensitization removing the circulating antibodies or inhibiting production of antibodies with no affection on immunological memory
Level v expert opinion
2 important developments have signicantly improved access to transplant for highly sensitized patients
1-kidney allocation system (KAS) in December 2014 prioritized organ offers for patients with high levels of anti-HLA sensitization. As a result, the median waiting time for highly sensitized patients with cPRA of 98%–100% has decreased from >19 years to 3.2 years
2-national paired exchange programs considered the best initial options for patients with either ABO or HLA-incompatible living donors.
So, desensitization of highly sensitized patients has decreased in recent years
Desensitizing treatments are expensive, resource intensive, and place patients at risk for morbidity associated with potent immunosuppression. Furthermore, these treatments remove circulating antibody or temporarily inhibit antibody production without signicant effect on immunologic memory. As such, there is a well-documented memory immune response following HLA-incompatible transplant, with postdesensitization antibody-mediated rejection (AMR) rates generally ranging from 25% to 50%.
Despite aggressive posttransplant DSA monitoring histologically identied AMR was detected in 29% of desensitized recipients
best option would be to avoid HLA-incompatible transplant whenever possible, although not necessarily at the expense of signicantly prolonged dialysis exposure while awaiting a compatible offer. When living donors are available, paired exchange should be attempted in order to avoid the cost and risk associated with desensitizing therapy as well as the posttransplant immune response that will likely translate into poorer long-term graft survival.
proceeding with desensitization for those highly sensitized patients without living donors, where paired exchange is not possible and expected wait time is considered unacceptable, may be a reasonable consideration. When considering this option, however, one should account for the published variability in both postdesensitization transplant rates as well as outcomes.
Level 5
Desensitization in Kidney Transplant: A Risky (but Necessary?) Endeavor for Those with Limited Options
Expert opinion, Level 5 evidence
Advances in transplanting highly sensitized patients had made improvement in transplant access:
1. change to the kidney allocation system (KAS) – prioritized organ offers for patients with high levels of anti-HLA sensitization.
· So, the median waiting time for highly sensitized patients with cPRA of 98%–100% has decreased from >19 years to 3.2 years
· Europe- focusing on organ allocation to sensitized patients based on acceptable mismatches has succeed in transplanting >1000 patients with excellent long-term outcomes
2. increased use of national paired exchange programs such as the National Kidney Registry
Data suggest that prior to KAS system – survival advantage for patients undergoing desensitization followed by live donor transplantation compared with those waiting for a compatible organ offer
But desensitizing treatments are expensive, resource intensive, and place patients at risk for morbidity associated with potent immunosuppression
Vo et al suggested:
· 90 highly sensitized patients undergoing desensitization with IVIG, rituximab, +/PLEX/tocilizumab, stratified by DSA status at the time of and following transplant
· AMR in patients with persistent pretransplant and posttransplant DSA (45%) and in patients who developed de novo DSA but were DSA negative at transplant 70%, compared with those with pretransplant DSA that disappeared (11%) or those with no DSA pretransplant or posttransplant (10%)
· all patients experienced similar graft survival with a median follow-up time of 2.9 years
· Conclusion- highly sensitized patients may benefit from desensitization and that the success of these programs relies on aggressive posttransplant antibody monitoring to identify those patients at higher risk for rejection and graft loss
· reported favourable results both in achieving transplant as well as acceptable posttransplant outcomes in desensitized patients receiving deceased donor transplants
other centres have failed to replicate these encouraging results using similar strategies
5-year data from the Mayo Clinic show significantly worse patient and graft survival in those undergoing desensitization versus HLA compatible transplant, as well as protocol biopsy-detected transplant glomerulopathy in 55% of desensitized versus 7% of HLA-compatible recipients
So, best option would be to avoid HLA-incompatible transplant whenever possible. Living donors are available, paired exchange should be attempted
Proceeding with desensitization for those highly sensitized patients without living donors, where paired exchange is not possible and expected wait time is considered unacceptable, may be a reasonable consideration
If decided for desensitization, paired exchange options should be exhausted, and a realistic estimate of wait time taking into account priorities for high cPRA patients under KAS should be considered
2.Once we opted for desensization, we need aggressive post-transplant mornitoring for DSA for the possibility post-desensitization immunologic injury
What is the take-home message addressed by this article?
Survival advantage for patients undergoing desensitization followed by live donor
transplantation compared with those waiting for a compatible organ offer.
Treatments remove circulating antibody or temporarily inhibit antibody production
without significant effect on immunologic memory. As such, there is a well-
documented memory immune response following HLA-incompatible transplant, with
post desensitization AMR rates generally ranging from 25% to 50%.
Aggressive posttransplant antibody monitoring to identify those patients at higher
risk for rejection and graft loss.
Best option would be to avoid HLA-incompatible transplant whenever possible,
although not necessarily at the expense of significantly prolonged dialysis exposure
while awaiting a compatible offer.
Desensitization its reasonable consideration for those highly sensitized patients
without living donors, where paired exchange is not possible and expected wait
time is considered unacceptable.
The risk/ benefit assessment of desensitization must be reconsidered
Desensitizing treatments are expensive, resource intensive, and place patients at
risk for morbidity associated with potent immunosuppression.
What is the level of evidence provided by this article?
Level of evidence V.
Plasamapheresis PP:
Removing DSAs from circulation. It’s non specific for antibodies removal, all plasma proteins are removed including clotting factors.
The removal of DSAs is short lived with DSAs rebounding to pre treatment level following reequlibration between intravascular and interstitial compartments.
It dose not affect ongoing DSAs production by plasma cells hence its poor choice for desensitization as sole therapy.
It’s side effects include coagulopathy,hypocalcemia, thrombocytopenia,hypotension and catheter related infection.
Therefore IVIg was added to PP.
Intravenous immunoglobuline IVIg derived from gamma globular fraction of plasma from pooled donors.
Its mode of action include:
Inhibit T and B cell proliferation
Inhibit cytokine production.
Inhibit complement activation
Inhibit maturation of dendritic cells.
Induce B_cells apposite.
The protocol for combination of IVIg and PP divided into 2 approaches
1. alternate day PP (no. Of sessions depend on titer of DSAs ) combined with low dose IVIg( 100 mg/kg).
2.PP alternating days with high dose IVIg (1_2 gm/kg).
Low dose IVIg with PP:
AMR , has been reported to be as high as 36%, with 100 % one year graft survival.
This protocol was modified to improve the high risk of AMR ,with the inclusion of ATG for induction,along with Rituximab and splenectomy. Despite that modification, AMR was still high with 43% and graft survival of 78% at 15 months. Same incidence risk was reported with a median follow up of 22 months.
Bortezomib: It is a proteasome inhibitor causing apoptosis of plasma cells. Its use saw transplant of 43% of sensitized patients with 12.5% developing de novo DSAs and 18.8% acute rejection.
Eculizumab: It is an antibody blocking cleavage of C5. If used in addition to IVIG and plasmapheresis, has shown risk of AMR in range of 7.7% to 11.8% as compared to 21.6% to 41.2% seen with IVIG and plasmapheresis, but with an increased risk of invasive infections.
Tocilizumab: It is an antibody against IL-2 receptor which, when used with IVIG in patients unresponsive to IVIG and rituximab, showed good results post-transplant with no AMR at 6 months and good graft function at 1 year post-transplant.
IgG degrading enzyme derived from Streptococcus pyogenes (IdeS): It causes proteolysis at Fc region of IgG. Its use has been shown to be associated with approximately 40% AMR which were treated. Long term effects including infections and malignancies need to be evaluated.
Benefits of desensitization:
Increases sensitized patients access to transplantation by decreasing cPRA & the number of unacceptable antigens for listing.
Patients with a cPRA of > 99.9% have the greatest need for desensitization.
Patients with a cPRA < 98% with an incompatible living donor or those on the waiting list for several years may also benefit from desensitization.
Decreases DSA prior transplantation in patients with positive XM to reduce the risk of immediate graft loss from hyperacute rejection.
Long-term risks of desensitization:
Difficult to determine because most of the studies that looked into this issue were short term.
Overall immunosuppression raises concerns of infections & malignancies.
Reduced survival, mostly related to infections, also reported.
Cost-effectiveness of desensitization:
Desensitization should be reserved for only those patients where all other possible options
are exhausted , it is a costly affair but is worth if used appropriately.
Take-home messages:
-For those highly sensitized patients:
With a living donor, if failed paired or unavailable kidney program, desensitization is an available option rather than being on dialysis or being on the waiting list for a deceased donor.
Without living donor: Prioritization by specific allocation system KAS decreased from >19 ys to 3.2 years increased the rate of deceased donors for some sensitized patients
– Data favoring desensitization plus living donor than being on the waiting list, as regards patient and graft survival, however this data before the PKD program.
– Desensitization protocols are associated with risk of potent immunosuppression (i.e. infection and malignancy), more acute rejection episodes (25-50%) due to persistent DSAs or de novo DSAs however comparable graft survival, more transplant glomerulopathy, subclinical ABMR
*level 5 (commentary article)
Desensitization treatment remove circulating antibodies and temporarily inhibit antibody production without affecting immunologic memory
It is expensive and increases the risk of morbidity due to potent immunosuppression.
It is better to avoid HLA incompatible transplant with consideration of the adverse effects of prolonged dialysis exposure
Paired exchange donation to avoid the risk associated with desensitization
Highly sensitized patients may proceed with desensitization to avoid unacceptable long waiting time.
Careful selection of patients according to health status and anti-HLA antibody status
Level 5
Desensitization in Kidney Transplant: A Risky (but Necessary?) Endeavor for Those With Limited Options
This paper is an editorial to a paper by Vo et al.
Access to transplantation has improved for highly sensitized patients due to;
1. Changes made in the kidney allocation system
2. National kidney paired exchange
This has shortened waiting time for highly sensitized patients from 19 to 3.2 years.
Has also reduced interest in desensitizing highly sensitized patients.
Drawbacks for desensitization measures; expensive, side effects, immunological memory persist, high rates of AMR post-desensitization.
Findings from a study by Vo et al are highlighted in this editorial.
A cohort study which looked at the post-desensitization immune response of 90 sensitized patients using IVIG, rituximab, +/−PLEX/tocilizumab.
High AMR rates in patients with antibodies pre or post-transplant.
Findings favoured desensitization in highly sensitized patients.
Other centres have not replicated these findings.
A study from Mayo clinic is highlighted which found transplant glomerulopathy in 55% undergoing desensitization compared to 7% in HLA compatible.
The author concludes by not recommending desensitization unless when faced with the choice of patients staying too long on the waiting transplant list.
This is level 4 evidence
Patients who are highly sensitized to allergens may benefit from desensitization, and the effectiveness of these programs is dependent on intensive post-transplant antibody surveillance to identify those patients who are at greater risk for rejection and graft loss, according to the findings.
If live donors are available, the matched exchange should be tried in order to avoid the costs and risks associated with desensitizing treatment, as well as the immunological response that will most likely result in inferior long-term graft survival after the transplant.
Because desensitization can still facilitate early better graft out com compared to haemodialysis, we can accept the desensitization option for those highly sensitized patients without living donors in situations where the paired exchange is not possible and the expected wait time is considered unacceptable. However, close post-transplant DSA monitoring is required to identify patients at risk for rejection and graft loss.
The use of national matched exchange programs is the greatest choice for patients who have live donors who are incompatible with their ABO or HLA.
These developments reduce the waiting time and desensitization protocols, which are expensive, resource-intensive, and associated with a risk of immunosuppression.
Level 5
based on this article, will you accept performing desensitisation of highly sensitised transplantation after running out of all options?
Any survival advantage (graft and patient)?
Yes I would accept doing desensitisation if there is no chance for paired exchange or no chance for KAS .
Despite the worse clinical outcomes and the high costs compared to regular transplantion , desnsetization versus being on dialysis treatment provide a better survival . At 3 years, the transplanted patients had a 14.7–17.6% greater probability of survival than those remaining on dialysis (1).
2 year patient survival was 95% and graft survival was 86% in 725 patients with DSAs who had kidney transplantation with different protocols , but the acute rejection rate was 36% and acute AMR rate was 28%.
Studies showed that AMR rates range between was 43% (15 months ) , 39% ( 22 months ) and 33% ( 2 years).
Graft survival range was found between 78% ( 15 months),89% ( 22 months) and 93% (at 2 years)
One study in 211 kidney recipients compared desensitization in living donation with dialysis or HLA-compatible transplantation over 8 years . Patient survival was :
for desensitized group versus dialysis-only group versus dialysis-or-transplantation group were as follows:
90.6%:91.1%:93.1%, at 1 year,
85.7%:67.2%:77.0% at 3 years,
80.6%:51.5% : 65.6% at 5 years
and 80.6%:30.5%:49.1% at 8 years (2)
1.Stanley C. Jordan, Jua Choi, Ashley Vo, Kidney transplantation in highly sensitized patients, British Medical Bulletin, Volume 114, Issue 1, June 2015, Pages 113–125, https://doi.org/10.1093/bmb/ldv013
2.Kuppachi, S. and Axelrod, D.A. (2020), Desensitization strategies: is it worth it?. Transpl Int, 33: 251-259. https://doi.org/10.1111/tri.13532
the evidence is V
home message
============
Patients who are highly sensitized, desensitization with consideration of
DSA state can provide them a chance for deceased kidney donation. The risk of AMR is still high approaching 45%. So it is not recommended if there is a chance for either of paired exchange donation or immediate KAS allocation
This is a cohort study .so the level of evidence is 2b
The article is an expert opinion so the level of evidence is 5
Dear all, please realize that this is a Commentary manuscript on an original work of :
Vo AA, Aubert O, Haas M, Huang E, Zhang X, Choi J, Peng A, Najjar R, Sethi S, Ammerman N, Lim K, Jordan SC. Clinical Relevance of Posttransplant DSAs in Patients Receiving Desensitization for HLA-incompatible Kidney Transplantation. Transplantation. 2019 Dec;103(12):2666-2674. DOI: 10.1097/TP.0000000000002691.
Thanks prof for more explanation.
II. Desensitization in Kidney Transplant: A Risky (but Necessary?) Endeavor for Those with Limited Options
What is the take-home message addressed by this article?
1. Recent changes to the KAS, which prioritized organ offers for highly sensitized patients (cPRA=98%–100%), reduced median waiting time from >19 years to 3.2 years. This & similar concepts in Europe, based on acceptable mismatches, allowed successful transplantation for >1000 patients with excellent outcomes.
2. The increased use of national paired exchange programs allowed more patients, with either ABO or HLA-incompatible living donors, to be transplanted.
3. These developments reduced the interest in desensitization of highly sensitized patients.
4. Limitations to published multicenter data that suggest a survival advantage for patients undergoing desensitization followed by live donor transplantation include:
– These data were collected before implementation of KAS
– Control groups were not enrolled in paired exchange programs. Desensitizing is expensive & resource demanding
– Morbidity associated with potent immunosuppression.
– Desensitizing treatments don’t address immunologic memory; they merely remove circulating antibodies or temporarily halt their production.
– High rates of post-desensitization AMR (25%-50%)
5. In a cohort of 90 highly sensitized patients undergoing desensitization, Vo et al concluded that highly sensitized patients may benefit from desensitization & that the success of these programs depends on aggressive posttransplant antibody monitoring to identify those patients at higher risk for rejection & graft loss:
– this cohort was largely of deceased donor transplant, unlike
the work by Orandi et al which showed survival benefit of
desensitization before living donor transplant.
– Desensitization in deceased donor transplant wouldn’t predict
transplant events.
-despite these challenges, Vo et al reported favorable results
& acceptable post-transplant outcomes in desensitized
deceased donor transplantations.
-other centers, however, failed to replicate these encouraging
results using similar strategies.
6. A 5-year data from the Mayo Clinic showed worse patient & graft survival as well as TG (by protocol biopsy) in patients undergoing desensitization versus HLA-compatible transplant.
7. From the above data, the best options would be:
1.To avoid HLA-incompatible transplant whenever possible, but not at the expense of very prolonged dialysis exposure while waiting a compatible offer.
2.To attempt paired exchange whenever living donors are available.
3.To reconsider the risk/benefit of desensitization
4,To opt for desensitization only in highly sensitized patients without living donors, where paired exchange is not feasible & would likely unacceptably prolong wait time.
What is the level of evidence provided by this article?
Level V: Commentary article
Desensitization in Kidney Transplant: A Risky (but Necessary?) Endeavor for Those with Limited Options
Highly sensitized patients undergoing desensitization for transplantation have been shown to be having survival advantage as compared to remaining on wait-list. The advent of kidney allocation system and paired exchange programs have increased chances of such patients receiving a compatible kidney, thereby having a positive impact on the graft survival.
Whenever possible, sensitized patients should be entered in a paired kidney exchange program. But it may not be possible in all scenarios. Hence in a highly sensitized patient without a living donor, not eligible for paired exchange program, and expecting an unacceptably long wait-period, it is prudent to desensitize the patient for transplant and keep a close follow-up post-transplant using DSA monitoring and protocol biopsies.
Level 5: Expert commentary
Yes I would go for desensitization in such a scenario.
Graft and patient survival is different for deceased and living donor transplant.
Mayo Clinic showed significantly worse patient and graft survival in those undergoing desensitization versus HLA compatible transplant.
Protocol biopsies detected TG in 55% of desensitized versus 7% of HLA compatible recipients.
Ideally HLA incompatible transplant should be avoided however not necessarily at expense of prolong dialysis exposure.
Paired exchange is better option if possible.
What is the take-home message addressed by this article?
1- Desensitizing treatments are expensive, resource intensive, and place patients at risk for morbidity associated with potent immunosuppression.
2- Desensitization treatments remove circulating antibody or temporarily inhibit antibody production without significant effect on immunologic memory.
3- highly sensitized patients may benefit from desensitization and that the success of these programs relies on aggressive post transplant antibody monitoring to identify those patients at higher risk for rejection and graft loss.
5- When living donors are available, paired exchange should be attempted in order to avoid the cost and risk associated with desensitizing therapy as well as the post transplant immune response that will likely translate into poorer long-term graft survival.
6- proceeding with desensitization for those highly sensitized patients without living donors, where paired exchange is not possible and expected wait time is considered unacceptable, may be a reasonable consideration.
What is the level of evidence provided by this article?
Level 5
Excellent
Transplantation is the best option for ESRD patients on dialysis ,highly sensitized recipients have limited options for transplantation.
kidney allocation system (KAS) and paired exchange programs have improved transplantation in sensitized patients ,decreased waiting time on dialysis and decreased the need for desensitization.
Although desensitization can be a rescue solution for very highly sensitized recipients ,but still there is many disadvantages.
*Desensitizing treatments are expensive, resource intensive.
* place patients at risk for morbidity associated with potent immunosuppression.
*It removes circulating antibody or temporarily inhibit antibody production without signifcant effect on memory cells with AMR rates generally ranging from 25% to 50%.
*5-year data from the Mayo Clinic showed worse patient and graft survival in those undergoing desensitization versus HLA-compatible transplant, as well as protocol biopsy-detected transplant glomerulopathy in 55% of desensitized versus 7% of HLA-compatible recipients.
*so the best option would be to avoid HLA-incompatible transplant whenever possible ,use paired exchange programme with living donor is better than desensitization.
*desensitization of highly sensitized patients with living donors, where paired exchange is not possible and expected wait time is considered unacceptable, may be a reasonable consideration.
*desensitization is centre based experience and no fixed protocol.
*Desensitization remains a good way to access transplantation for highly sensitized recipients when there is no other available options and still better option than waiting on dialysis.
*Close follow up of DSA and protocol biopsy of desensitization transplanted patients with early detection of subclinical AMR with early treatment may help to improve graft outcome and patient survival.
desensitization in Kidney Transplant: A Risky (but Necessary?) Endeavor for Those with Limited Options
Level 2 evidence
Take-home messages:
Desensitization is a way to make transplantation accessible for highly sensitized recipients.
• It gives good chance than long waiting on hemodialysis for the patient.
nevertheless; it should only be carried out if there is no other option like
Paired kidney donation.
• It just removes the DSA temporally and has no effect on the memory
cells which can trigger an immune reaction to the allograft causing AMR and
ultimately graft failure. About 55% of the desensitized recipient developed
transplant glomerulopathy on protocol biopsy as compared to 7% of
HLA-compatible recipients.
• Desensitized patients need more aggressive follow-up with DSA
monitoring and protocol biopsy, which will increase the cost of already costly
procedure
• There is no universal protocol for desensitization. it is centre
experience-dependent and this makes a difference in outcome; so we can not
generalize the results.
• It carries multiple risks to the patients like infection and
malignancy, so need to select patients carefully.
Desensitization in Kidney Transplant: A Risky (but Necessary?) Endeavor for Those With Limited Options.
The home message:
1-Try to avoid HLA in-compatible transplantation as much as we can.
2-When living donors are available, paired exchange should be attempted in order to avoid the cost and risk associated with desensitizing therapy.
3-If paired exchange not available and the patient is highly sensitized and on waiting list for long time with an incompatible live donor option, desensitization should be considered and outweigh the risk/ benefit ratio .
4-Desensitized patients is high risk for AMR post kidney transplant so should be strictly followed by DSA and kidney biopsy.
Level of evidence is 2 B
Dear Dr Mohamed
It can not be level 2 B
IT IS LEVEL 5…..It is expert opinion (level 5)
# What is the take-home message addressed by this article?
#The development of the following options improved renal transplantation in highly sensitized patients:
# Change to the kidney allocation system (KAS) for highly sensitized patients with high levels of DSA (cPRA of 98%–100%).
– organ allocation to sensitized patients based on acceptable mismatches has successful transplantation with excellent long term outcomes.
# Use of national paired exchange programs best option for patients with either ABO or HLA incompatible living donors.
# As a result of these developments it decrease the waiting time and desensitization protocol which are expensive, resource intensive, risk of immunosuppression and these treatments remove circulating antibody or temporarily inhibit antibody production without significant effect on immunologic memory.
# Patients may benefit from desensitization with post transplant DSA monitoring to identify risk for rejection and graft loss.
# Thus we can accept the desensitization option for those highly sensitized patients without living donors, where paired exchange is not possible and expected wait time is
considered unacceptable, because desensitization is still facilitate early better graft out com compared to heamodialysis
but we need close post transplant DSA monitoring to identify risk for rejection and graft loss.
# What is the level of evidence provided by this article?
# Level 2
IT IS LEVEL 5…..It is expert opinion (level 5)
The article is like editorial comment so evidence is level 4
The take-home message is that we should not consider desensitization as the first option in very high sensitized patients as desensitization has little to do with memory cells. son late or chronic rejection is still a challenge. donor exchange is preferable. My opinion is with desensitization if this is the only chance after explaining to donor and recepient
Desensitization in Kidney Transplant: A Risky (but Necessary?) Endeavor for Those with Limited Options
Take home messages
1- Avoid HLA-incompatible transplant when possible
2- Paired exchange program is a favorable option for highly sensitized patients which will decrease the costs, risks and post-transplant immune response of desensitization which lead to poor graft outcome
3- Desensitization is an option if paired exchange program is not feasible and there is expected long waiting time
The level of evidence is IIb (individual cohort study)
Article Summery:
Highly sensitized patients had two important breakthroughs to improve their chance of transplantation:
1- Kidney allocation system (KAS) which prioritized organ offers for patients with high Anti HLA Abs with cPRA 98-100% which decreased median waiting time from >19 yrs to 3.2 yrs.
2- The use of national paired exchange program.
Desensitizing treatments are expensive, resource intensive, and place patients at risk for morbidity associated with potent immunosuppression also these treatments remove circulating antibody or temporarily inhibit antibody production without significant effect on immunologic memory leading to Post desensitization AMR which range from 25-50%.
Vo et al studied post desensitization immune response in a cohort of highly sensitized 90 patients underwent desensitization with IVIG, Rituximab +/-PLEX/Tocilizumab with mostly deceased donor transplant and concluded that highly sensitized patients may benefit from desensitization with favorable graft outcome and that the success of these programs relies on aggressive posttransplant antibody monitoring to identify those patient at higher risk for rejection and graft loss other centers have failed to replicate these encouraging results using similar strategies like Mayo Clinic experience.
In Vo et al study Despite aggressive posttransplant DSA monitoring in the current report by Vo et al, histologically idented AMR was detected in 29% of desensitized recipients. And this was associated with significant risk of graft glomerulopathy and failure (this is a limitation of the Vo et al study, because the median follow up period was 2.9 yrs, which may not be enough to detect these worse graft outcomes).
Not sure about the level of evidence of the study.
Level of evidence is 2
Home messages:
If highly sensitized patient had no chance for living donor & exchange program, I will use desensitization for him because it will improve both graft & patient survival.
IT IS LEVEL 5…..It is expert opinion (level 5)
– The kidney allocation system (KAS) and national paired exchange programs facilitate transplants in highly sensitized patients, reduce waiting time for transplantation and decrease the need for desensitization.
-National paired exchange programs are the best options for patients with either ABO or HLA-incompatible living donors.
– KAS increases rates of deceased donor transplants but not all highly sensitized patients.
Desensitization is recommended for:
· highly sensitized patients without living donors and long waiting time
· If a paired exchange is not possible for the patient.
-Desensitizing treatments are expensive, resource-intensive, and place patients
at risk for morbidity associated with potent immunosuppression.
-Desensitization remove circulating antibody or temporarily inhibit antibody production without significant effect on immunologic memory which may be associated with AMR.
-Highly sensitized patients may benefit from desensitization and they need aggressive posttransplant DSA monitoring.
-Desensitization is associated with transplant glomerulopathy , AMR and graft failure.
–Avoidance of HLA-incompatible transplant whenever possible.
-Level of evidence :2b
Decent summary of the paper but why do you think that commentary by an expert provides 2b level of evidence?
IT IS LEVEL 5…..It is expert opinion (level 5)
☆Desensitization in Kidney Transplant: A Risky(but Necessary?) Endeavor for Those With Limited Options
♧Home messages:
Desensitizing treatments:
____________________________
▪︎ Are expensive, resource intensive, and place patients at risk for morbidity ass with potent immunosuppression.
▪︎Remove circulating antibody or temporarily inhibit antibody production without significant effect on immunologic memory (there is a well-documented memory immune response following HLA-incompatible transplant, with post desensitization (AMR))
▪︎Conducted by IVIG, rituximab, +/-PLEX/tocilizumab, and stratified by DSA status at the time of and following transplant.
▪︎Give benefits to highly sensitized patients and the success of these programs relies on aggressive post-transplant antibody monitoring to identify those patients at higher risk for rejection and graft loss.
▪︎Some studies shows worse patient and graft survival in those undergoing desensitization versus HLA compatible transplant, as well as protocol biopsy-detected transplant glomerulopathy in desensitized pts.
Important points:
___________________
▪︎Avoid HLA-incompatible transplant whenever possible.
▪︎Paired exchange is superior to desensitization when living donors are available (but paired exchange is not a feasible option for most highly sensitized recipients).
▪︎ The risk/ benefit assessment of desensitization must be reconsidered.
▪︎ Proceeding with desensitization for those highly sensitized patients without living donors may be a reasonable consideration.
▪︎Variability in desensitization is influenced by many factors:
1. Specific desensitization regimen.
2. The cross-match assay(s) utilized.
3. The level of cross-match reactivity that
a given center considers “acceptable.”
▪︎ Careful selection of patients for desensitizing treatment is mandatory to avoid serious harm
▪︎ If desensitization is considered for highly sensitized patients, expectations should be tempered. Paired exchange options should be exhausted, and a realistic estimate of
wait time taking into account priorities for high cPRA patients.
♧Level of evidence: Level II
why do you think that commentary by an expert provides level II evidence?
IT IS LEVEL 5…..It is expert opinion (level 5)
Take home message is that,desensitization program for highly sensitized patients is not the perfect solution. For several reasons,as follows:
2 important developments have significantly improved access to transplant for highly sensitized patients (defined as cPRA of 98%_100%):
1st is change to kidney allocation system KAS,prioritized organ offers for highly sensitized patient. Wait time reduced from 19 years to3.2 years. Based on acceptable mismatches.
2nd is the increased use of national paired exchange program HLA highly sensitized patients with HLA_incompatible living donors.
Desensitization treatment: draw backs
1)Expensive,resource intensive with high morbidity associated with potent immunosuppressive.
2)Technically Desensitization treatment remove circulating antibodies or temporarily inhibit antibody production without significant effect on immunologic memory. AMR risk post Desensitization is generally 25 to 50 %.
Vo et al study revealed high rate of AMR post desensitization, in patients with persistent pretransplant and post transplant DSA (45%), and (70%) of patients who developed De novo DSAs but were negative at transplant time.Risk of developing De novo is 25%.
Furthermore 5_year Data from Myo Clinic revealed transplant glomerulopathy 55% of desensitized vs7% of HLA compatible recipients.
Therefor desensitization treatment is to be avoided ,but in few patients who failed to be managed by the protocols mentioned earlier.
It’s level II evidence based study
IT IS LEVEL 5…..It is expert opinion (level 5)
Over the last 2 decades, 2 developments have improved access to kidney transplantations for highly sensitized patients. First, a change to the kidney allocation system which gave recipients access to transplantation regardless of sensitization status. Second is the use of national paired exchange programs such as the National Kidney Registry, for better matching for ABO or HLA-incompatible living donors.
As a result of these developments, desensitization of highly sensitized patients has decreased.
Desensitizing treatments are associated with increased risk of post-transplant infections and malignancy, along with expenses. These treatments aim to remove circulating antibody or temporarily inhibit antibody production without significant effect on memory cells.
The provided article support the transplant of highly sensitized recipients regardless of the origin of the donor kidney. However, it is better to avoid HLA-incompatible transplant whenever possible.
When living donors are available, paired exchange should be attempted before the decision to proceed with transplantation especially if desensitization is recommended.
Sensitized patients are still at risk of acute antibody mediated rejection due to preformed or de novo DSA even following aggressive desensitization treatment. Desensitization treatment is more effective when living donor is selected.
Posttransplant outcomes in desensitized patients receiving deceased donor transplants are better comparing to patients on the waiting list. But in this particular group, posttransplant protocol biopsies and monitoring of immunosuppression serum levels are crucial to detect early and subclinical rejections.
What is the level of evidence provided by this article
In highly sensitized patients the best options would be – paired kidney donation and exchange in case of living donor and kidney allocation system for deceased donor. If paired exchange is not available and there is long waiting list then desensitization protocol can be considered.
Non compatible transplantation should be avoided as –
-There is risk of infection and malignancy and desensitization is only transient process and rebound effect may induce worse rejection.
– The desensitization protocols are costly
-Overall outcome are worse with TG and AMR
-Desensitisation outcome can variable between transplant centres and will depend on method of selection of patients, drug protocols, and close monitoring post transplant
What is the level of evidence provided by this article
-Take home message
AMR rates are increased in patients with persistent DSA and with de novo DSA
Desensitization can be a successful option for highly sensitized cases but needs close monitoring of DSA to detect early rejection liability .
Paired kidney exchange programs is another option to avoid risk and cost burden associated with desensitization treatment, as desensitization risk versus benefit outcomes need to be evaluated for each case .
Paired kidney exchange should be considered for patients with high c PRA , considering the waiting time for prioritizing such cases .
-Level of evidence II
Highly sensitised patients have high risk of transplant loss despite using desensitisation protocol because temporary inhibition of antibodies production and with long term may develops de novo DSA which lead to loss of graft also high dose of immunosuppressive drug are very expensive and may expose patients to serious opportunistic infection and side effects of drug.
So highly sensitised patients better to avoid transplant and locking for another option like Kidney allocation system help to increase rate of deceased donor transplant or
Shift patients to Parried donor exchange program which facilitates transplant of patients with ABO and HLA incompatible with others compatible.
But if there’s no option to high sensitised patients better do transplant with high dose of desensitisation immunosuppressive drug with extensive monitoring for DSA level and biopsy protocol because high risk of transplant glomerulopathy
Finally transplant better than patients become for long time on dialysis.
Q2: Evidence II cohort study
What is the take-home message addressed by this article?
Although desensitization of patients undergoing kidney transplantation is an option that has considerably reduced the waiting time in a specific group of patients sensitized over the years for various reasons (pregnancy, blood transfusion, vaccination, viral diseases, previous transplantation).
Highly sensitized patients should prioritize compatible living donors and only when they are not available to follow the Kidney Allocation System (KAS) deceased donor protocol.
When the waiting period for an organ becomes unacceptable, the patient should be desensitized and proceed to transplantation.
However, the patient must be informed of the risks involved and the need for a high-cost treatment, risks of infection due to prolonged important immunosuppression, and more aggressive monitoring with DSA protocols and biopsies.
The individualization of the follow-up of each patient is essential in choosing both the sensitization protocol and the maintenance immunosuppression to be performed.
What is the level of evidence provided by this article?
Prospective cohort (level 2b evidence).
What is the take-home message addressed by this article?
1- kidney allocation system (KAS) that prioritized organ offers for these patients.
2- national exchange paired program.
What is the level of evidence provided by this article?
· Desensitizing treatments are expensive, resource-intensive, and place patients at risk for morbidity associated with potent immunosuppression.
· Highly sensitized patients may benefit from desensitization and the success of these programs relies on aggressive post-transplant antibody monitoring to identify those patients at higher risk for rejection and graft loss as in Vo et al analysis
· When living donors are available, the paired exchange should be attempted in order to avoid the cost and risk associated with desensitizing therapy as well as the post-transplant immune response that will likely translate into poorer long-term graft survival.
level 2
Take home message
National paired kidney donation and exchange in case of living donor and Kidney allocation system (KAS) for the deceased donor are the best options for transplantation in highly sensitized recipients (HLA and ABO-incompatible). Desensitization protocol can be the option only if the patient is highly sensitized and no living donor or paired exchange is available and waiting list time is unacceptable. Desensitization has a transient effect and cannot affect memory cells, which can induce more potent AMR, transplant glomerulopathy , and worse long-term patient and graft survival. According to the Mayo Clinic data, transplant glomerulopathy occurs in more than 55% of desensitized patients in five years when compared to HLA-compatible recipients (7%). Desensitization protocols are expensive and increase the chances of infection and malignancy and also their results vary between centers due to different desensitization regimens used, proper selection of recipient who can tolerate the strong immunosuppressive therapy without adverse consequences, method of XM and the level of cross-match reactivity that is acceptable in a particular center. The best option is to avoid HLA-incompatible transplantation whenever possible, but if desensitization needed, then close monitoring of DSA all through the transplantation follow up period is needed.
LEVEL OF EVIDENCE: 2
The article addressed these points:
Ø Desensitization is a risky approach as it may be associated with many complications. Moreover, the effect of removal of the DSA is usually temporary due to the persistence of the memory immune response.
Ø Desensitized recipients still have a lower allograft survival than those who received a compatible allograft.
Ø The priority given by different allocation systems to highly sensitized recipients on the waiting list has dramatically improved the waiting time for such patients. Therefore, the desensitization option became less attractive than before.
Ø Paired kidney donation proved to be the best option for highly sensitized patients to obtain the best-matched allograft, provided that the patient has a willing living donor.
Level 2