4. A 41-year-old CKD 5 male, blood group A1 (Rh +ve) who received a kidney offer from his cousin who is blood group B (Rh +ve). The recipient both anti-B IgG and IgM antibody titres are 1/8 on the day of the operation. 101 mismatch. Negative FCXM. No DSA. Primary function with s Cr 89 µmol/L one week after the operation. As per unit protocol, kidney biopsy was performed at the end of week one. Biopsy showed C4d staining (see below) and H&E reported uremarkable (not shown). Anti-B IgG antibody titre was reported on the day of the biopsy to be 1/8 (no change from the pre-transplant titre) with sCr 96 µmol/L. Tacrolimus level is 10 ng/ml (on triple immunosuppression).
- Explain the findings?
- What is your management?
Dear All
Thank you for choosing not to biopsy this patient, agree, it is an adaptation process.
Assume you checked the Anti-B IgG antibody titre 2 weeks later and came back as 1/16 and without any change in serum creatinine. Will you biopsy this kidney? Why?
Please refer to the guidelines.
the risk of late AMR and after 2week is low realted to ABOi so again screen this patient for HLA antibodies .
iwill not biopsy unless HLA Abs postive or rising in serum creatinie.
supervise adherence and intensive immunosupression thearpy
mointoring graft function and serial Abs tire(Anti-B IgG)
I will not biopsy the patient as there is no evidence of allograft dysfunction and the rise in antibody titer after 2 weeks in the back ground of normal allograft function is consistent with accommodation. AMR secondary to ABOi transplantation is very rare after the first 2 weeks.
No indication for kidney biopsy.
Still no need for biopsy as the AMR is very rare after 2 weeks post transplantation of ABOi pairs.
increase of only one dilution (minor change ) is not significant. the daily increase of 2 dilutions prompts treatment for AMR. one dilution alarms us to plasmapheresis planning but here one dilution over one week seems unimportant
BTS guideline page: 55
Excellent, yes, 2-dilution indicates biopsy regardless of the kidney function. You have read the BTS guidelines
Increased isoagglutinin titer to 1/16 ( not represent a cause to worry or proceed to biospy) as :
_ post transplant isoagglutinin titer less than 1/32 was shown to be safe and not associated with AMR.
_ timing of that rise ( 3 weeks after transplant) is less likely to be associated with AMR.
_ stable graft function is the most assuring prognostic factor here.
_ previous biospy shows immunological accomodations of graft to isoagglutinin.
_ so ,plan of management is to revise immunosupressives prescript and follow up titer if doubling daily or in short intervals or associated with detected DSA, worsening graft function or protinuria ..we will proceed to biopsy and prepare for PEX
Excellent, yes, 2-dilution indicates biopsy regardless of the kidney function. You have read the BTS guidelines
Thanks dear professor
Dear All
2-dilution indicates biopsy regardless of the kidney function. It is very clear in BTS guidelines. Therefore a titre of 1/32 is the cutoff for biopsy.
Best Answers
Mahmud Islam
Mai Shawki
No. this situation does not warrant a kidney biopsy as:
1) There is no change in graft function
2) Only one dilution increase in antibody titres.
But this increase will warrant a repeat sample next day, to see the trend of rise in antibody titres.
If there is further rise in titres, then biopsy and treatment in form of extracorporeal removal of antibodies is warranted.
A 2 dilution rise would have warranted treatment initiation.
Minor changes ( titers changing by one dilution (e.g. 1/4 to 1/8)) may prompt a plan of plasmapheresis or immunoadsorption for the following day if the following day’s antibody titer is worse. If the change is two dilutions, e.g. 1/4 to 1/16 from the previous day, then treatment may be initiated that day.so, kidney biopsy will be done at this point.
No need for biopsy the level is 1 dilution .
according to BTS guidelines for antibody incompatible transplantation,
there is no need to monitor anti-B IgG after 1st 2w of ABOi transplantation as the risk of rejection is low especially with stable graft function.
during the 1st 2w of ABOi transplantation daily follow-up of IgG titer should be done by the same method of hemagglutination if there increase to 1/16 close monitoring of graft function and IgG titer should be done if the next day appears to be 1/32 direct treatment should be considered even before doing kidney biopsy as rejection is very accelerated
I wouldn’t go for biopsy as rebound is very rare in ABO-antibodies providing stable graft function
I wouldn’t biopsy this patient providing stable graft function but I will keep an eyes on the agglutination titer for follow up
Better no biopsy AMR rare 2 weeks post transplant
1) Explain the findings?
C4d deposit at peritubular cells. No evidence of allograft rejection.
2)What is your management?
Continue Tac base immunosuppressive regimen.
serial renal profile, FK level, and DSA level.
ABOi kidney transplantation, there is no change in the Anti-IgG antibody titre pre and post-transplant 1/8, stable renal function
The biopsy showing linear deposition of C4d without features of tissue injury on protocol biopsy
No treatment is needed
Follow up for DSA, serum creatinine, and anti-B IgG level.
Assume you checked the Anti-B IgG antibody titre 2 weeks later and came back as 1/16 and without any change in serum creatinine. Will you biopsy this kidney? Why?No ,because phenomena of Accommodation
Desensitization protocols are aimed to decrease antibody titre below a certain threshold ( 1/8) at the time of ABOi kidney transplantation and during the first 2 weeks after surgery. Thereafter, even a rebound of anti-A/B antibodies does not appear to harm the kidney transplant, a phenomenon that is called Accommodation
Accommodation is defined as a phenomenon whereby graft rejection is avoided despite reemergence of incompatible antibody.
The mechanism by which endothelial cell posttransplant humoral injury was avoided, possibly due to changes of antibody specificity, avidity, affinity and alteration of the antigen structure.
By 2006, the American Society of Transplantation established a consensus on the accommodation status and added the presence of C4d on the peritubular capillaries . The pathogenesis of the accommodation seems to be due to the presence of a low titer of antibodies, with low affinity and with the blockage of complement activation .
The findings consist of stable graft function post ABOi transplantation with low level of anti-B IgG antibody. The biopsy revealed C4d deposition without any significant evidence of tissue injury. This can be explained by adaptation or accommodation.
Plan of management:
To continue the same plan of management without a need for any intervention or added therapy.
Explain the findings?
What is your management?
· No active management is required
· Follow up for DSA, serum creatinine, and anti-B IgG level. In case that there is 2 dilution increase in anti-IgB AB titer a renal biopsy is required to look for histological features of ABMR and prepare to start therapeutic plasma exchange
The patient underwent ABO incompatible renal transplant with baseline anti B titre of 1:8 pre transplant. The patient has a post transplant Anti B titre of 1:8 with no increase in creatinine. The images shown are a part of protocol biopsy which shows normal light microscopy without features of AMR. C4d stain is positive. C4d positivity is indicative of Accomodation in the post renal transplant status in ABOi renal transplantation…This does not warrant any treatment as it indicates graft accommodation…
Management involves no other medical therapy at this moment…Patient needs to be monitored for the anti B titre upto 2 weeks after renal transplantation….Any 2 fold rise in the anti B titre within 2 weeks is an indication to do a renal biopsy to detect ABMR..
biopsy revelas c4d staing positive, no features of cellular infeltration or rejection.
also, the titre is accepted 1/8
it seems accepted.
It looks as ABOi transplant accommodation, no further work up is needed.
Explain the findings?
PTC C4d stain, which can be seen in ABOi transplant as in this case, it called accomodation
What is your management?
Graft function is stable, anti-B IgG titer 1/8, protocol biopsy was reassuring, nothing to be done apart from follow up and optimization of IS.
this is c4d +ve in the glomerulus and PTC which has no significance in ABOi kidney transplantation and is considered accommodation as long as there is stable graft function
there is no indication for active management just optimization of the immunosuppressive regimens and frequent monitoring of the graft function
Findings
The findings indicate accommodation of graft. The patient has positive C4d staining and not any more features of rejection.
Accomodation is an acquired resistance of an organ to immune mediated damage. Accomodation is a good response to transplant since it prevents acute types of humoral injury. However, it can affect the graft negatively too. BY preventing acute injury, Accomodation allows chronic processes to progress over time.
Management :
Careful monitoring of anti B IgG levels, DSA, serum creatinine levels, and tac dose.
References
No active lesions on the biopsy
No acute elevation of the anti-ABO antibody titer
Normal serum creatinine level
Tacrolimus level is within the target
So the positive C4d staining in the graft biopsy can be explained by accommodation.
The process of accommodation can be defined as the presence of positive C4d staining without evidence of ABMR.
Just follow up for DSA level, serum creatinine level, and anti-B IgG level.
If there is an increment in any one of them, then a graft biopsy should be done and treatment of ABMR should be started after confirmation of the diagnosis by biopsy
Findings can be explained by accommodation, a common phenomenon in ABOi transplant considering no graft dysfunction, no histological finding of AMR, anti-B IgG titer did not increase compared with before transplantation and presence of C4d deposition in peritubular capillaries. It may be attributed to controlled anti-A/B antibody exposure to antigens early post transplant
Management:
Close monitoring of graft function, DSA & anti-B antibody titer and continuation of the same drug regimen.
References:
Salvadori M, Tsalouchos A. Current protocols and outcomes of ABO-incompatible
kidney transplantation. World J Transplant 2020; 10(7): 191-205
· Explain the findings?
· The biopsy showed C4d deposition in peritubular without evidence of tissue damage .This is accommodation phenomena occur when patient received ABO compatible transplant due to circulating ABO antibodies .
· What is your management?
· Continue same plan
· Close monitoring RFT anti -B IgG antibody titre and TAC level .
This is accommodation, which is a frequent phenomenon in ABOi transplant as the patient has no graft dysfunction , no histological finding of AMR, anti-B IgG titer is the same as before transplantation and has C4d deposition in peritubular capillaries.He is for close follow up with monitoring of graft function, DSA and anti-B antibody titer .The FK level is suitable so continue on the same prograf dose
C4d staining in PTC without hisytologic features of ABMR ( NO nicrocirculation affection ) in the context of ABOi KT is explained as accommodation .in which state the persisting low level of Anti A/B ( B in this case ) with changes in Ag /Ab specificities that renders these Abs non reacting to target Ags .
Management : keep monitoring kidney function , repeat Anti B IgG titre at the end of week 2 ( after which period the ABMR is much less likely as the process of accommodation is almost settled ) , push up the dose of tavroloimus as it is below the target at this time .
The slide show c4d positive in ptc without evidence of microvasular injury
This is considered as accommodation which occurred in ABOI
Immunologic accommodation — The presence of detectable isoagglutinin titers, AB endothelial antigen expression, and positive peritubular capillary (PTC) C4d staining despite the absence of any histologic evidence of ABMR has been thought to represent ABOI immunologic accommodation
NO need for further treatment
In contrast to transplantation in the HLA-sensitized patient, accommodation appears to be a frequent phenomenon after ABOi kidney transplantations and is often associated with C4d deposition in peritubular capillaries of allograft biopsies. An accommodation phenotype may be achieved by the controlled anti-A/B antibody exposure to antigens in the early phase after kidney transplantation. About 2 weeks after successful transplantation, accommodation is established and even high anti-A/B antibody exposure does not harm the kidney transplant.
Reference
imageChristian Morath1*, imageMartin Zeier1, imageBernd Döhler2, imageGerhard Opelz2 and imageCaner Süsal2. ABO-Incompatible Kidney Transplantation. Front. Immunol., 06 March 2017.
explain the finding: ABOi transplantation
as the graft function is stable and there are no other features of acute rejection, the C4d staining in this graft is explained by accommodation phenomena.
management plan:
repeat the Isoagglutinin titer daily for the next week if no change no need for biopsy. after 2 weeks the risk of rejection is low in ABOI trx if graft function stable
. Explain the findings?
-The biopsies showed peritubular C4d deposition without other histological features of ABMR.
This is ABOi-Kidney Transplant, No DSA.
in ABOi.
What is your management?
This is accommodation, a frequent phenomenon in ABOi transplant as the patient has no graft dysfunction, no histological finding of AMR, anti-B IgG titer is the same as before transplantation and has C4d deposition in peritubular capillaries.
It may be due to controlled anti-A/B antibody exposure to antigens early post transplant
Close follow up with monitoring of graft function, DSA and anti-B antibody titer continuation of the same drug therapy.
Salvadori M, Tsalouchos A. Current protocols and outcomes of ABO-incompatible
kidney transplantation. World J Transplant 2020; 10(7): 191-205
This case is ABOi living kidney donor transplantation with 101 HLA mismatches and recipients’ blood group A1. One week after transplantation the recipient had stable kidney function without a significant increase in serum Cr level, and there was no increase in anti-B IgG antibody titer (1/8). H&E staining demonstrated unremarkable findings and positive C4d staining was detected in IF and IHC. The aim of desensitization protocols is the reduction and maintenance of anti A/B antibodies (isoagglutinins) during the first 2 weeks after transplantation below a threshold that is considered to be safe (e.g., <1:32 in tube technique). In this case, the anti-B IgG antibody is less than 1:32, thus it is at a safe limit. Thereafter, even when anti-A/B antibodies recur at high levels, they will not harm the kidney transplant, a phenomenon that is called accommodation which is accompanied by C4d positivity without evidence of AMR. Monitoring of kidney function is appropriate management in this patient.
Explain the findings?
The findings shows accommodation phenomenon,occurs within the first 2 weeks post-transplantation in ABOi-KT(C4d deposition in peritubular capillaries without other signs of AMR or deterioration of graft function) with no rise of serum creatinine nor Ab titre
What is your management?
Follow up of Ab titre in 2 weeks
If graft dysfunction occurred after 2 weeks, DSA level and repeat biopsy should be done with CMV and BKV levels
Explanation of the findings
The case is an example of ABO incompatible transplantation, which goes smoothly till now, guided by adequate drug level monitored, no elevation in anti B antibody levels and no significant change in serum creatinine level.
Biopsy shows only C4D peritubular linear deposits which can be considered physiological finding due to accommodation phenomenon that occurs early after transplantation 2 weeks post-operative described by the presence of antibodies but however they are non-injurious.
Management plan:
Immunosuppressive protocol as scheduled (triple therapy tacrolimus, MMF, prednisolone)
Adjusted by drug level monitoring,
Monitoring of IG B antibodies,
Protocol biopsy according to center protocol not on demand.
frequent monitoring of serum creatinine according to protocol of the center.
In this patient, there is cd staining documented by IHC (peritubular ), IF as expected both glomerular and peritubular capilaries are stained.
Without an increase in titer and without a remarkable Cr increase (TC level is 10) is compatible with the accommodation phenomenon. so followup is enough
The allograft biopsy shows and staining at PTCs with normal graft function and acceptable ABO antibody titer and tacrolimus level. C4d positive staining in this case is related to accommodation due to ABOi-KT. So, there is no need for specific treatment only follow up is sufficient in this case.
Explain the findings? -peritubular C4d deposition in the ptc Shawn in the biopsy without other histological features of ABMR. -This patient had a stable Anti-B IgG antibody titre that was reported on the day of the biopsy to be 1/8 (no change from the pre-transplant titre) and RFT.within normal Tac level. -These findings goes with accommodation which is the phenomenon of lack of rejection in the presence of circulating ABO antibodies and positive C4d deposition in the biopsy due to complement activating and it is also responsible for kidney protection .
What is your management?
-Close follow-up: Anti-B IgG antibody titre ,DSA ,RFT ,TAC level.
– Continue on the same line of management plan.
-Protocol biopsy.
presence of C4d staining in ABOi transplant recipient without evidence of ABMR called accommodation phenomena’
stable creatinine and low titre of anti-B IgG more supportive fore accommodation
follow up of AB titre during hospitalization or in the clinic in the first 2 weeks
# Explain the findings?
This ABOi kidney transplant recipient suggest accommodation phenomenon seen in first few weeks posttransplant.
with stable anti B antibody titres and graft function in the first week posttransplant,
the graft biopsy shows a positive C4d staining without any other histological evidence of ABMR.
# What is your management?
Continue the same management with
routine follow up of graft function and serial anti B antibody titres monitoring
If there is graft dysfunction or increase in anti B antibody tires then measurement of DSA as well as kidney ptotocol biopsy should be done
Explain the findings
This patient had ABOi renal transplant ( donor Blood group B and recipient blood group A). HLA mismatch 101. Negative FXCM. No DSA. Anti IgG and IgM titres are 1/8. Stable renal functions. Adequate Tac trough levels.
Renal biopsy shows C4d staining only. No AMR
C4d Staining can be seen in ABOi renal transplantation without evidence of AMR. This is due to phenomenon of accommodation in early post transplant phase.
What is your management
No change in management is required. I will like to monitor Anti B antibody titres. I will consider renal biopsy and measure DSA if there is deterioration of renal functions and proteinuria
Explain the findings?
The findings represent accommodation phenomenon
Which occurs within the first 2 weeks post-transplantation in ABOI-KT
Where there is C4d deposition in peritubular capillaries without other signs of AMR or deterioration of graft function.
In this case there were no rise of s creatinine nor Ab titre
What is your management?
No change of treatment plane .
Follow up of Ab titre during hospital stay and in the following visits for 2 weeks
If graft dysfunction occurred after2 weeks its mostly not due to isoagglutinins and DSA level and another biopsy should be done
This finding is called ACCOMODATION, as here C4d positive with anti-B titre stable without any histological feature of rejection.
So, here nothing to be done and further monitor of dsa will be done if there is graft dysfunction.
1. Explain the findings?
-The biopsies showed peritubular C4d deposition without other histological features of ABMR.
-This patient had a stable Anti-B IgG antibody titre that was reported on the day of the biopsy to be 1/8 (no change from the pre-transplant titre) and RFT.His tacrolimus level is 10 ng/ml
-These findings suggest accommodation which is the phenomenon of lack of rejection in the presence of circulating ABO antibodies complement activating and it is also responsible for kidney protection over a long period.
What is your management?
– Continue on the same management plan.
-Close follow-up: Anti-B IgG antibody titre ,DSA ,RFT ,TAC level.
-Protocol biopsy.
This is a patient with an ABO incompatible transplant, with stable anti B antibody titres and stable graft function 1-week post-transplant with adequate tacrolimus trough levels.
The graft biopsy shows a positive C4d staining without any other histological evidence of AMR.
This is due to the phenomenon of accommodation, whereby a C4d positive staining is seen in absence of any evidence of AMR. It is seen in ABO incompatible transplants in first few weeks.
In this scenario, continue same treatment.
Routine follow-up of graft function and serial anti-B antibody titres monitoring for first 3-4 weeks is enough.
If there is graft dysfunction or increase in anti-B antibody tires, then measurement of DSA and a kidney biopsy will be required.
Explain the findings?
The low titre of anti-B IgG antibody( no change from pre transplant base line ) and the absence of DSA in combination with C4d deposit in the allograft biopsy of this ABOi kidney transplant recipient suggest accommodation .
Accommodation refers to a condition in which a transplant (or any tissue) appears to resist immune-mediated injury and loss of function. ABO-incompatible kidney transplants exhibit heightened risk of antibody- mediated rejection during the first several weeks up to approximately 1 mo after transplantation. Susceptibility to early rejection is mitigated by intrinsic resistance of nucleated cells and tissues to complement mediated injury and by the immediate response to complement activation on cell surfaces.
What is your manage?
If ABO- incompatible transplants are accommodated to ongoing production of anti-blood group antibodies, then one cause of rejection could be the loss or diminution of accommodation, as might occur with inter current illness or infection.
The risk for acute rejection will increase in this patient when there is ;
1- loss of ability to absorb and metabolize donor-specific antibodies leading to the reappearance or to an increase in the level of donor-specific antibodies in blood.
2-Loss restoration of accommodation which would be marked by a decrease in anti-donor antibody levels in blood.
Accordingly DSA and anti B-IgG should be followed .
Reference ;
1- Haas M, Rahman MH, Racusen LC, et al. C4d and C3d staining in biopsies of ABO- and HLA-incompatible renal allografts: correlation with histologic findings. Am J Transplant. 2006;6:1829-1840.
2. Koch CA, Khalpey ZI, Platt JL. Accommodation: preventing injury in transplantation and disease. J Immunol. 2004;172:5143-5148.
3. Cascalho M, Platt JL. Harnessing B cells in immunotherapy. Immunotherapy. 2016;8:237-239
1. Presence of c4d postive staining or deposits in such case of ABO I transplantation is just accomodations (means c4d deposition and antibody adsorption within the graft without immunological mediated damage).
_ this is confirmed by stable titer of anti B isoagglutinin, stable graft function, negative DSA , within target range tacrolimus trough level.
_ no signs of immune mediated graft damage as concluded by HX and EO staining so not fulfill the diagnosis of AMR.
_ ABO I transplant represent one of the causes of c4d positivity without AMR as an accomodations phenomenon.
2. Management plan …no extra management will be needed .
Just regular follow up of such ABO I transplant, anti B isoagglutinin titer thrice weekly in 2 ND week then weekly till end of 1 st month ( high risk for isoagglutinin rebound and AMR), follow up serum creatinine and A/C ratio as per protocol.
_ surveillance biopsy as per protocol.
_ indication biopsy once graft dysfunction or progressive protinuria as any case
Explain the findings?
This patient underwent an ABOi transplant. The recipient blood group is A so, he was excpected to have anti B. his anti-B IgG titer was below the cut off for desensitization. Anti-B IgG did not increase from the pre-transplant titer .The HLA mismatch was 101 .clinically the patient has mild increase in serum creatinine.(7.8%). His tacrolimus level is within target. C4d staining in the graft biopsy can be explained by accommodation as there are no of neither clinical nor other histological abnormalities.
What is your management?
Monitor DSA level and anti-B IgG level at regular interval.
ABMR is the first cause of graft loss in transplantations involving ABOi. The risk for ABMR is related to the isoagglutinin level at transplantation and to the presence of anti-HLA antibodies
Salvadori, Maurizio, and Aris Tsalouchos. “Current protocols and outcomes of ABO-incompatible kidney transplantation.” World journal of transplantation vol. 10,7 (2020): 191-205. doi:10.5500/wjt.v10.i7.191
.
Explain the findings?
Renal biopsy taken from patient ABOi kidney transplantation.
As mentioned biopsy showed no signs of histological injures .
Showed linear peritubular and glomerular c4d positive staining on IF and IHC which is called Accommodation(1).
C4d deposition without signs or symptoms of rejection can be observed in accommodated kidney(2).
What is your management?
=No specific treatment is needed at time being as no pathological changes and accepted isoagglutin titer.
=Serial follow up of anti B -IgG titer and DSA.
=Monitoring of renal function tests.
References:
1-C4d Deposition without Rejection Correlates with Reduced Early Scarring in ABO-Incompatible Renal Allografts. Mark Haas, Dorry L. Segev, Lorraine C. Racusen, Serena M. Bagnasco, Jayme E. Locke, Daniel S. Warren, Christopher E. Simpkins, Diane Lepley, Karen E. King, Edward S. Kraus, Robert A. Montgomery,JASN Jan 2009, 20 (1) 197-204; DOI: 10.1681/ASN.2008030279.
2-Lynch & Platt, 2010.
– The findings are :
· An ABO incompatible transplantation
· Low anti B Ig G and Ig M (1/8)which is stationary
· 101 mismatch ,Negative FCXM.
· No DSA
· Serum Creatinine 89umol/l-reached 96 umol/l which is nearly stable
· Biopsy showed C4d staining of glomerular endothelial cells, and surrounding peritubular capillaries.
C4d deposition did not correlate with ABMR, and it may not have any diagnostic or therapeutic relevance.
· Tacrolimus level is 10 ng/ml on triple immunosuppression which is acceptable
Indicative of Graft Accommodation
Which can can be explained by the following mechanisms:
Ø an alteration in the functional properties of anti-donor antibodies
Ø variation in the antigens
Ø the development of organ resistance to humoral injury due to expression of anti-apoptotic genes (1)
– For the current status no evidence of ABMR therefore no certain therapy would be given,
Follow up will be advised with monitoring of
DSA level and MFI titer
Anti B Ig G and Ig M level
Renal function
Proteinuria
Tacrolimus trough level
And if any deterioration of graft function , protocol allograft biopsy will be needed.
Reference
1- Okum M . et al . Current protocols and outcomes of ABO-incompatible kidney transplantation based on a single-center experience . Transl Androl Urol 2019;8(2):126-133
Explain the findings?
What is your management?
What exactly were the findings?
C4d staining in peritubular capillaries was found to be localized.
AMR does not present itself histologically. The amount of creatinine in the blood is normal. There is no DSA Tacrolimus level that is within the desired range.
All of these characteristics indicate accommodation.
What is the nature of your management?
Although there is no need for active care at this level, frequent monitoring of antibody titers and graft function is very important- 2-3 times per week for the first month, then weekly until 3 months post-transplant, and then yearly after that.
A renal biopsy should be performed in the event of graft malfunction, and the patient should be managed appropriately if there are histologic signs of AMR.
▪︎In this scenario of a 41 old male who received a kidney offer from his cousin a per unit protocol, kidney biopsy which was performed at the end of week one. Biopsy shows features of graft accommodation due to ABO compatibility ( the recipient is blood group A1 and the donor is blood group B).
☆NOTE:
__________
▪︎Accommodation refers to a condition in which a transplant appears to resist immune-mediated injury and loss of function [1].
▪︎ Accommodation was discovered and has been explored most thoroughly in ABO-incompatible kidney transplantation.
▪︎In this setting, kidney transplants bearing blood group A or B antigens often are found to function normally in recipients who lack and hence produce antibodies directed against the corresponding antigens.
☆Management of graft accommodation:
▪︎No specific treatment is needed
▪︎Follow up by repeated DSA levels and protocol biopsies
_____________________
Ref:
Mayara Garcia de Mattos Barbosa et al.”Accommodation in ABO-incompatible organ transplants. Xenotransplantation.
C4D deposition in PTC and glomeruli, without evidence of of rejection ,in ABOI patient
,suggest accommodation.
Follow up with Serum DSA 3 weekly for the first month, weekly for the first 2-3 months,
then yearly .
In patient with a posttransplant antibodies more than 1:16 , a kidney biopsy is done
,otherwise protocol biopsy and follow up.
Case of ABOI with maintained anti AB antibodies titre and stable kidney function with target level of tacrolimus. Presence of C4d deposition along peritubular capillarities without evidence of ABMR.
It’s called a phenomena of graft accommodation.
It’s management keep on same triple immunosuppressive agents and close monitoring of anti AB antibodies weekly and protocol for renal biopsy at 3 / 12months.
This is the typical serological finding in ABO incompatible kidney transplantation. This is a positive C4d staining in an otherwise stable post kidney transplant status, normal kidney function, negative DSA, and tacrolimus level within the therapeutic target. These findings define accommodation.
The plan is standard followup.
Explain the findings?
Isolated C4d staining in peritubular capillaries
No histological manifestations of AMR
Normal serum creatinine level
No DSA
Tacrolimus level is within the target.
All these features represents accommodation.
What is your management?
No active management needed at this level so regular follow up of antibody titers and graft function is highly needed- 2-3 times per week for the first month then weekly till 3 months post-transplant then annually.In case of graft dysfunction ,renal biopsy should be done and manage accordingly if there is histologic manifestations of AMR.
REFERENCE:
Dominy K., Willicombe M., Al Johani T., Beckwith H., Goodall D., et al. Molecular Assessment of C4d-Positive Renal Transplant Biopsies Without Evidence of Rejection. KIReports, 2019;4:148-158
The presence of PTC and glomerular capillaries positive staining for C4d in the absence of evidence of MVI [ glomerulitis and PTC capillaritis ] is indicative of accommodation , biopsy showed patent glomerular capillaries . Immunoflouriscent study revealed diffuse glomerular and PTC deposition of C4d.IHC of PTC showed deposition of C4d.
There is no rise in the Anti B titer, and even in presence of rise in the titer , the underlying pathology is accommodation , and no indication for intervention.
I think it is phenomenon of graft Accommodation and requires just close follow up.
IHC & IF staining show C4d positive in both PTC & glomerular capillaries.
C4d positive staining on graft biopsy is not specific for ABMR. It can occur in ABOi transplant without evidence of tissue injury & graft dysfunction also it can present occasionally in ABOc transplantation without evidence of rejection.
Presence of positive C4d staining in PTC with out evidence of histological or serological signs of rejection is associated with good graft outcome, but presence of both PTC & glomerular capillaries diffuse C4d staining is associated with graft dysfunction & IFTA.
Management:
References:
ABOi KT with stable graft function and stable level of antiB/A abs , tacrolimus trough level acceptable , and the protocol biopsy 1 week after the transplant shows the diffuse CD4 staining both in IHC staining and the IF section with diffuse glomerular staining with no associated graft injury indicate graft accommodation will need closely monitor the ABs titer for the first 2 weeks with graft function , tacrolimus trough level , any increase of the anti BIgG antibodies then consider repeat graft biopsy and treat accordingly.
Dear All
I made a summary of ABOi transplantation;
See below:
Dear All
Let us agree on a few points regarding ABOI transplantation
1. The cut off for desensitisation is 1/256. The outcome of desensitisation of higher titre (1/512 and above) is associated with poor outcome
2. A2 cannot be considered blindly as a universal donor. There are a few cases where the recipient reported a titre of 1/512 against the A antigen. Therefore, the titre is essential.
3. ABOi and the presence of DSA, would be better in the paired exchange scheme
4. If the paired exchange is not available, then desensitisation (Rituximab, IVIg and PE)
5. IgG is more important than IgM. IgM is a big molecule that can be removed easily during the PE and is well suppressed by immunosuppression. Therefore, most transplant centres consider IgG rather than IgM in their consideration for transplantation.
6. Many of the scenarios missing the crossmatch. It is essential to check the crossmatch before making decisions.
7. Titre of 1/16 (according to the guidelines) or less is safe to proceed without desensitisation. Our cut off in Sheffield is a titre of 1/8
8. ABOi transplantation is cheaper than dialysis and associated with better patient survival. I have asked students to stress these points to consider ABOi transplantation to expand the donor pool.
9. You can tell that these are the learning objectives of these scenarios.
10. The risk of rejection in the post-operative period is associated with the maximum preoperative titre, and results from the Tokyo Women’s Hospital indicated very poor survival in patients with a titre of 1/128 or greater, though some recent reports do however indicate that these high antibody levels (≤ 1/256 IgG) can be successfully crossed. Titre ≤ 1/256 IgG is acceptable for desensitization and titre ≤ 1/8 IgG is acceptable for transplantation. Preoperative maximum anti-A/B IgG (not IgM) titres correlate with the long-term graft survival in ABO-incompatible living kidney transplantation. There is no association between anti-A/B IgM titres and the post-transplant outcome. IgM is such a large molecule, which has a small volume of distribution, so it is easy to remove by plasmapheresis and associated with less rebound after transplantation – so even if the titre starts high, it is less likely to be a limiting factor in terms of transplantation (please see the MCQs).
11. The simplest and most common method to remove antibodies from plasma is therapeutic plasma exchange, in which large amounts of plasma are withdrawn and replaced with colloid solutions. This procedure eliminates approximately 20% of the anti-ABO IgG antibodies and 30% of the anti-ABO IgM antibodies with each session. However, this technique is not sufficiently selective as it removes not only anti- ABO antibodies but also removes coagulation factors, hormones, and antiviral and antibacterial immunoglobulin G (IgG) and immunoglobulin M (IgM). The removal of these factors increases the risk of bleeding or infection. However, this technique is by far the least expensive means of removing antibodies.
Dear Prof,
This summary is wonderful, practical and up to the point.
can we have similar summary [guideline] for HLA incompatible transplantation
Thanks prof