1. A 31-year-old male received a kidney transplant from his brother, 111 mismatch, no pre transplant DSA, primary function. He had basiliximab induction; Tacrolimus based triple immunosuppression as maintenance. S Cr was stuck at 200 µmol/L. He developed a new DSA (against B53 with MFI 4500) post-transplantation. C4d was negative by both IHC and IF. The biopsy shown below shows lymphocyte infiltration in the glomeruli and in the peritubular capillaries:
- What is your diagnosis?
- What is your management plan?
Dear All
This is a classical case of C4d negative AMR. Remember, C4d is not essential to diagnose AMR if the other criteria are fulfilled (evidence of tissue injury and the presence of DSA).
In the UK, we will treat this patient using PE and IVIg (150 mg IV after each session of PE).
We do not use these fancy drugs such as bortezomib or Eculuzumb as they are very expensive.
Of course regular monitoring of DSA (every 3 months for the first year and twice-yearly afterwords).
Prof I have a question regarding using Eculizumab in the above mentioned scenario assuming it’s available and regardless the cost.
As this patient has no C4d staining on biopsy that’s should mean that this rejection is mostly non-complement fixing and to distinguish we will need to do C1q assay which is the first to be stained in the complement cascade.
As Eculizumab working by specifically binding to the terminal complement component 5 (C5). I think if it’s used it will not work in this case. Is that correct ?
We can user other DSA inhibiting drugs if plasmapheresis and IVIG was not working such as:
Dear All
In order to diagnose TCR or mixed rejection, you need to have clear evidence of tubulitis. We can not rely on cellular infiltration to diagnose TCR.
When suggesting treatment, please tailor the treatment to your available resources.
Waiting for more replies and feedback on our comments
Diagnosis :
ABMR with negative c4d
due to the presence of glomeruloitis,peritubular capillaritis and lymphocytic infiltrations with the presence of DSA in absence of tubulitis
Need of frequents DSA monitoring
close followup
protocol of renal biopsy may be needed
Treatment depends on
high level of tacrolimus and plasma exchange and IVIG
Rituximab , bortezomib, or Eculuzumb may be needed in resistant cases but they are expensive
C4d negative AMR
Management plan: plasmapheresis and IVIG
serial monitoring of DSAs
1.What is your diagnosis?
AMR , C4D -ve
Glomerulitis with lymphocyte infiltration and peri-tubular capillaritis, no evidence of tubulitis to suggest a mixed rejection.
C4d is negative by IHC and IF(not essential in diagnosis of AMR)
New De novo DSA is present against B53 with MFI 4500.
2. What is your management plan?
No role of ATG as there is no evidence of associated TCMR
Treatment of ABMR
Plasmapheresis +IVIG
Serial monitoring of DSA and serum creatinine levels.
Bortezomib or Eculizumab or Rituximab but they are expensive.
The patient had DSA detected in his serum and histolgical evidence of Antibody mediated rejection (in the term of glomerulitis and peritubularitis) but the C4d stain was negative ,this put him in the category of C4d negative AMR so the treatment plan should include plasmapheresis with small dose IVIG and rituximab .
1) What is your diagnosis?
Antibody medicated Graft Rejection. C4d Negative
2)What is your management plan?
IV IG and plasma exchange.
May consider Bortezomib or Eculizumab if no financial issue.
Transplant gloerulopathy with heavy lymphocytic infiltration , negative C4d stain positive circulating DSA the possible diagnosis is acute AMR.
Treatment :plasma exchange + IVIG + Rituximab
Glomerulitis and pertubular capillary lymphocyte infiltration
No tubulitis
C4d negative
DSA positive
most likely AMR
methylprednisolone
plasmapheresis
IVIG
5 session
Rituximab after last session
monitor DSA level
monitor CNI trough level
There is dense infiterlare with lymphocytes in the biopsy.
Antibody mediated kidney rejection, of the C4d negative type.
using the strong tools:
sessions of plasmapharesis + Intravenous Ig.
What is your diagnosis?
o The renal pathology slides is showing glomerulitis with lymphocyte infiltration and peri-tubular capillaritis, no evidence of tubulitis to suggest a mixed rejection.
o However, C4d is negative by IHC and IF(not essential in diagnosis of AMR)
o New De novo DSA is present against B53 with MFI 4500.
o The diagnosis is C4d negative ABMR(no mention about the timing of rejection or the patient compliance)
What is your management plan?
o Pulse methyl prednisolone and check TAC level; keep high TAC level until biopsy result is available. No role of ATG as there is no evidence of associated TCMR
o Treatment of ABMR
1. Plasmapheresis 5-7 sessions.
2. IVIG 100-200 mg/KG after each PE session
3. Rituximab 375 mg/m2 after the last session of PE
4. Serial monitoring of DSA and serum creatinine levels.
5.Some centers use medications like Bortezomib or Eculizumab but they are expensive and not available in many centers
References:
Hand book of kidney transplantation 6th session
Lecture of DR Tariq Abbas
Diagnosis
Serum creatinine is stagnant at 200 micro mol/L. Patient developed DSA post transplant. C4d tested negative. Biopsy shows lymphocytic infiltration in glomeruli and in peritubular capillaries.
Diagnosis would be C4d negative AMR. Patient has DSA post transplant and is biopsy shows tissue injury evidenced with lymphocytic infiltration, glomerulitis and peri tubular capillaries inflamed.
Differentials for this case would include
Treatment
C4d negative ABMR
Biopsy showed: Glomerulitis with lymphocytic infiltrates, peri-tubular capillaritis
Negative C4d in IHC, new serum DSA
IV methyl-prednisolone 0.5-1 g/day for 3 days.
Plasma exchange and IVIG
Augmentation of IS medications: Tacrolimus+ MMF+ prednisolone
Regular Check of DSA, Tacrolimus levels.
Close monitoring of Renal function tests.
Q1- AMR with negative C4d.
Q2- pulse methylprednisolone
Plasmapheresis
IVIG
What is your diagnosis?
This patient has +ve DSA with high titre plus lympocytic infiltration to glomeruli and peri tubular capilari but C4d is negative .
this patient has C4d negative ABMR . AS C4d positivity can be replaced by
What is your management plan?
treatment of ABMR consists of
1- plasma exchange 5 session of 1.5 plasma volume , daily or every other day .
2- IVIg 100- 200 mg/kg after each plasma exchange .
3- plus minus rituximab .
4- in refractory cases bortezomibe may has arole.
5- other treatmenr include
C4d negative AMR
TTT:
MP 500 mg for 5 days + plasma exchange.
IVIG, Rituximab.
DSA and graft function monitoring
CNI levels monitoring
Diagnosis is
C4D negative active Antibody mediated rejection
Tratment
*pulse steroids (high dose)
*plasmapharesis 5-7 sessions
*IVIG 100 mg/kg after each session
Plus augmentatiin of immunosupression
Plus measure DSA 3times in 1st year
And twicw weekly in following years
What is your management plan?
* pulse steroid 500 mg for 3 days .
* plasmapheresis 1- 1.5 volume day after day followed by IVIG 100mg/kg after each session .
* augment immunosuppression.
* monitor DSA level every 3 month , kidney function if no improvement , we can add rituximab .
A 31-year-old male received a kidney transplant from his brother, 111 mismatch, no pre transplant DSA, primary function. He had basiliximab induction; Tacrolimus based triple immunosuppression as maintenance
. S Cr was stuck at 200 µmol/L. He developed a new DSA (against B53 with MFI 4500) post-transplantation. C4d was negative by both IHC and IF. The biopsy shown below shows lymphocyte infiltration in the glomeruli and in the peritubular capillaries.
* What is your diagnosis?
Early post-transplant ABMR with disturbed renal panel with de novo DSA mainly against HLA class II with C4d negative.
* Highly significant MFI .
* biopsy shown glomerulus with by PAS stain shown glomerulitis and peritubular capillarities with interstial inflammation .
According to the Banff 2013 classification,8 all of the following 3 features are required for the diagnosis of acute AMR:
1. Histologic evidence of acute tissue injury defined by the presence of one or more of the following:
a. Glomerulitis (g >0) or peritubular capillaritis (ptc >0)
b. Intimal or transmural arteritis (v >0)
c.Acute thrombotic microangiopathy (TMA) of no other obvious cause.
d. Acute tubular injury of no other obvious cause
2. Histologic evidence of current/recent antibody interaction with vascular endothelium, defined by at least one of the following:
a. Linear C4d staining in the peritubular capillaries
b. At least moderate microvascular inflammation (g þ ptc >2)
c. Increased expression of tissue gene transcripts
indicative of endothelial injury
3. Detection of DSAs (HLA or non-HLA) in the serum.
REFERENCES
1. Terasaki PI. A personal perspective: 100-year history of the humoral theory of transplantation. Transplantation. 2012 April 27;93(8):751-756. doi: 10.1097/TP.0b013e3182483713.
2. Djamali A, Kaufman DB, Ellis TM, Zhong W, Matas A, Samaniego M. Diagnosis and management of antibody-mediated rejection: current status and novel approaches. Am J Transplant. 2014 Feb;14(2):255-271. doi: 10.1111/ajt.12589.
3. Mauiyyedi S, Pelle PD, Saidman S, et al. Chronic humoral rejection: identification of antibody-mediated chronic renal allograft rejection by C4d deposits in peritubular capillaries. J Am Soc Nephrol. 2001 Mar;12(3):574-582.
A 31-year-old male received a kidney transplant from his brother, 111 mismatch, no pre transplant DSA, primary function. He had basiliximab induction; Tacrolimus based triple immunosuppression as maintenance
. S Cr was stuck at 200 µmol/L. He developed a new DSA (against B53 with MFI 4500) post-transplantation. C4d was negative by both IHC and IF. The biopsy shown below shows lymphocyte infiltration in the glomeruli and in the peritubular capillaries.
* What is your diagnosis?
Early post-transplant ABMR with disturbed renal panel with de novo DSA mainly against HLA class II with C4d negative.
* Highly significant MFI .
* biopsy shown glomerulus with by PAS stain shown glomerulitis and peritubular capillarities with interstial inflammation .
According to the Banff 2013 classification,8 all of the following 3 features are required for the diagnosis of acute AMR:
1. Histologic evidence of acute tissue injury defined by the presence of one or more of the following:
a. Glomerulitis (g >0) or peritubular capillaritis (ptc >0)
b. Intimal or transmural arteritis (v >0)
c.Acute thrombotic microangiopathy (TMA) of no other obvious cause.
d. Acute tubular injury of no other obvious cause
2. Histologic evidence of current/recent antibody interaction with vascular endothelium, defined by at least one of the following:
a. Linear C4d staining in the peritubular capillaries
b. At least moderate microvascular inflammation (g þ ptc >2)
c. Increased expression of tissue gene transcripts
indicative of endothelial injury
3. Detection of DSAs (HLA or non-HLA) in the serum.
REFERENCES
1. Terasaki PI. A personal perspective: 100-year history of the humoral theory of transplantation. Transplantation. 2012 April 27;93(8):751-756. doi: 10.1097/TP.0b013e3182483713.
2. Djamali A, Kaufman DB, Ellis TM, Zhong W, Matas A, Samaniego M. Diagnosis and management of antibody-mediated rejection: current status and novel approaches. Am J Transplant. 2014 Feb;14(2):255-271. doi: 10.1111/ajt.12589.
3. Mauiyyedi S, Pelle PD, Saidman S, et al. Chronic humoral rejection: identification of antibody-mediated chronic renal allograft rejection by C4d deposits in peritubular capillaries. J Am Soc Nephrol. 2001 Mar;12(3):574-582.
*ABMR
New DSA with high mfi
Also histopathology picture
*ttt
Plasmapheresis
IVIG
Also pulse steroids after biopsy taken
Maintenance therapy kept in high dose for at least next 3 months
Follow up DSA level every 3 months
Patient has C4d negative ABMR
Treatment could include PE on daily basis or on alternate days guided by DSA titer ,IVIG, myethylprednisolone 500mg-1g for 3 days
PE and IVIG act through removal of DSA with immunomodulation .Additionally, augmentation of maintenance immunotherapy is required with close periodic monitoring of DSA
diagnosis-
C4d- acute ABMR,
Management plan-
I.V. methylprednisolone 500 for 3 days,
Plasmapharesis – 5- 7 sessions,
IVIg 100 mg/kg after each session of PE,
Augment maintenance immunosuppression,
start cotrimoxazole prophylaxis,
monitor s.creatinine, urea regularly,
monitor DSA every 3 monthly in 1st year and then twice yearly afterward
Regarding the diagnosis:
This patient is suffering from acute active ABMR C4d –ve based on the DSA’s, peritubular capillaritis and the glomerulitis
Regarding the management plan ( transplant center experience ) :
Maintaining an acceptable trough tac levels 10-12
Starting
5 -7 sessions of Plasmapheresis followed by IVIG 500-700 mg/kg following the last session
Mabthera 375 mg/m2 2 weeks after the IVIG and may be followed by 2nd dose after another 2 weeks
Follow up of DSA and serum creatinine.
Diagnosis is C4d negative ABMR,
biopsy shows glommluritis and peritubular capillaritis
treatment
plasmapheresis 6sessions
IVG 100 mg kg after each session of plasmapheresis
methylprednisolone 0.5 -1g for 3 days
Rituximab
augment maintenance immunosuppression therapy
monitor KFT.DSA develops post-TX
if no response, rebiopsy
What is your diagnosis?
ABMR AS PATIENT HAS NEW DSA PLUS TISSUE INJURY IN THE FORM OF CELLULAR INFILTRATE .
What is your management plan?
THIS PATIENT REQUIRE PLASMAPHARESIS PLUS IVIG WITH MONITORING OF DSA Q 3 MONTHES IN FIRDT YEAR ACR REGULARY
What is your diagnosis?
This patient has DSA against B53 with MFI 4500 and increased creatinine 200mcmmol/lH&E stain showed glomerulitis and peritubular capilaritis ( g>0, ptc>0) so, its ABMR
But C4d stain is negative, but C4d may be absent in ABMR
What is your management plan?
Treatment:
I would like to follow TTS recommended regimes:
FDA Antibody-Mediated Rejection Workshop in 2017 as well as Kidney Disease: Improving Global Outcomes (KDIGO) in 2010 was that PLEX and IVIG could be regarded as a standard of care for acute active AMR, despite the weakness of evidence in support of efficacy
Rationale for using PLEX and IVIG is to combine removal of circulating DSA with immunomodulation of the antigraft immune response and in particular modulation of the B-cell response
IVIG has been shown to inhibit B-cell responses by the Fc portion of the Ig binding the Fc fragment of IgG2b receptor on B cells, and sialylated IVIG binds CD22, inducing apoptosis of mature B cells. IVIG also functions as a scavenger of activated complement.
Monitoring:
I would like to:
Monitor DSA post treatment
monitor creatinine and UPCI level
Kidney biopsy post treatment ( less favorable)
Carrie A. Schinstock,et al: Recommended Treatment for Antibody-mediated Rejection After Kidney Transplantation: The 2019 Expert Consensus From the Transplantation Society Working Group
My diagnosis is c4d negative Abmr
This patient should be treated with-
Therapeutic plasma exchange followed by IvIg 100mg/kg, no of sessions according to dsa level.
If there is no response that is no decrement of sr cr within 5days, then should be treated with IV ATG.
Maintainance immunosuppression should be increased along with cotrimoxazole prophylaxis.
Polyoma virus pcr monitoring to be done
1 – What is your diagnosis ?
The pacient has C4d-negative antibody-mediate rejection
2 – What is your management plan ?
The most common treatment for antibody-mediate rejection is:
– plasmapheresis;
– followed by low dose intravenous immunoglobulin (IVIg 100mg/Kg)
Dx : C4d -ve AMR ( tissue evidence of glomerulitis g>0 , and capillaritis PTC >0 ) , caused by dnDSA ( no pre Tx DSA ) .
management :
MP pulse 500 mg for 3 days
plasma exchange + IVIG 200 mg /kg after PE sessions
Augment maintenance IS
DSA screening thereafter
What is your diagnosis?
What is your management plan?
Diagnosis:
Management Plan:
handboook of kidney transplantation by Gabriel M Danovitch
What is your diagnosis?
C4d negative AMR
What is your management plan?
Methylprednisolone for five days associated with plasma exchange
If kidney function does not improve after treatment, start rituximab
DSA and graft function monitoring
CNI monitoring
C4d AMR .
Would go for plex
IVIG
Rituximab
C4d negative antibody mediated rejection
Nigam LK, Vanikar AV, Kanodia KV, Patel RD, Suthar KS, Patel HV. C4d-negative antibody-mediated rejection: A pathologist’s perspective and clinical outcome. Saudi J Kidney Dis Transpl [serial online] 2018 [cited 2022 Apr 1];29:39-49. Available
I would treat the patient in a similar way like other forms of ABMR
Plasma exchange
Proteosome inhibitors (Bortezomib)
IV human immunoglobulin
Post -renal transplantation development of denovo DSA with significant MFI and graft biopsy shows lymphocytic infiltration in the glomeruli and peri tubular capillaries with negative C4d goes with the diagnosis of C4d negative AMR .
Treatment:
Pulse Methylpredinisolone 500mg /day for 3-5 days followed by exchange plasmapheresis 1-1.5 volume every other day for 5 sessions with IVIG after each session
If no response go for Retuximab single dose .
A 31-year-old male received a kidney transplant from his brother, 111 mismatch, no pre transplant DSA, primary function. He had basiliximab induction; Tacrolimus based triple immunosuppression as maintenance. S Cr was stuck at 200 µmol/L. He developed a new DSA (against B53 with MFI 4500) post-transplantation. C4d was negative by both IHC and IF. The biopsy shown below shows lymphocyte infiltration in the glomeruli and in the peritubular capillaries:
early post transplant dearranged kidney functions and donovo DSA against class 1 b with significant MFI
biopsy done >>> unsuffient bipsy on the right side one glomerulus stained by PAS stain glomerulitis (G2) ,peritubular capilaritis and interstitial inflammations .there is no blood vessels
the immunoperoxidase showed -ve c4d stain
aaccording to banff 2017 diagnosis of ABMR depend on 3 items
-evidence of tissue injury (glomerulitis and peritubular capillarities)
-evidence of interaction between antigen and antibodies ( capillartities and glomerultis)
-evidence of antibodies (DSA or c4d)
offcourse early rejection with DSA against class I mostly associated with C4D +ve because its iGg 1,3 which mostly compement fixing but it can occure dueto multiple causes like sample errors or injury by non complement dependent mechanisms
interstitial inflammation may be related to mixed cellular rejection but as long as i have no tubulitis and no vessels to comment so this diagnosis is excluded according to current biopsy results
our center protocol
early ABMR can be treated with plasmapharesis 5 session using albuimn EOD with exchange 1.5 plasma volume
at the final session we can give IVIG 0.5gm/kg followed by one or two doses of rutiximab
cmv pcr and sv40 stain in biopsy should be excluded
The histological appearance of lymphocytic infiltration in the glomerular and peri tubular capillaries, with the negative C4d staining and the presence of DSA with significant MFI support the diagnosis of C4d negative AMR .
Treatment ;
1- methyl prednisolone 500 mg / day for 3-5 days
2-plasmapheresis (1-1,5 volume on alternative days + IVIG 100 mg/kg after each session.
3-Augment immunosuppressant level .
4- DSA and graft function monitoring .
5- add rituximab if no improvement .
Reference:
1.Recommended Treatment for Antibody-mediated Rejection After Kidney Transplantation: The 2019 Expert Consensus From the Transplantion Society Working Group Carrie A. Schinstock, MD, Roslyn B. Mannon, MD, […], and Philip J. O’Connell, Ph,
2-Cooper JE. Evaluation and treatment of acute rejection in kidney allografts. Clinical Journal of the American Society of Nephrology. 2020 Mar 6;15(3):430-8.
What is your diagnosis?
According to revised Banff 213 classification, Acute active antibody mediated rejection
as there is microvascular inflammation in glomeruli and peritubular capillaries (evidence of acute tissue injury and recent/current antibody interaction with vascular endothelium) and serologic evidence of DSA
No transplant glomerulopathy
What is your management plan?
Tacrolimus trough level and adjust dose accordingly
Pulse solumedrol for 3 days till result of biopsy confirmed, then plasmapheresis every other day followed by low dose IVIg 100 mg/Kg after each session
Rituximab 375mg/m2 given after last session of plasmapheresis
Should ensure patient adherence as de novo DSA is new DSA detected after 3 months post transplant mostly due to underimmunosuppression may be due to non-adherence, intended by physician or variability of metabolism of immunosuppressive drugs.
(1)Haas M, Sis B, Racusen LC, et al. Banff 2013 meeting report: Inclusion of C4d- negative antibody- mediated rejection and antibody- associated arterial lesions. Am J Transplant. 2014;14:272-283
(3) Schinstock CA, Mannon RB, Budde K, Chong AS, Haas M, Knechtle S, Lefaucheur C, Montgomery RA, Nickerson P, Tullius SG, Ahn C. Recommended treatment for antibody-mediated rejection after kidney transplantation: the 2019 expert consensus from the transplantation society working group. Transplantation. 2020 May;104(5):911.
(3) Cooper JE. Evaluation and treatment of acute rejection in kidney allografts. Clinical Journal of the American Society of Nephrology. 2020 Mar 6;15(3):430-8.
as this was low risk case basiliximab was chosen. aside from the basal creatinine seems to be increased with evidence of rejection presented by de novo DSA MFI 4500. although MFI is high . we need to adjust the tacrolimus level of course but apart of that as we have evidence of rejection we need to give steroid high dose but with plasmapheresis and IVIG. immuadsorption can be done if available. AMR can be without cd staining as in this case
Reference:
1.Recommended Treatment for Antibody-mediated Rejection After Kidney Transplantation: The 2019 Expert Consensus From the Transplantion Society Working Group
Carrie A. Schinstock, MD, Roslyn B. Mannon, MD, […], and Philip J. O’Connell, PhD
Diagnosis:
Late AMR due to de novo DSA
1.lymphocyte infiltration of the glomerulus and peritubular
2.C4D-NEGATIVE
3.Denovo DSA.
the most common form of AMR is associated with dnDSA. In general, dnDSA is a new DSA detected after >3 months post transplant in the context of inadequate immunosuppression which is either due to patient nonadherence, physician directed, or genetically determined variability in metabolism of immunosuppressive drugs. This form of AMR often presents with allograft dysfunction and concomitant or preexisting TCMR.
Mangment plan:
the aims of treatment are to preserve renal function, reduce histological injury, and reduce the titer of donor-specific antibody,
recommendations for treatment are largely based on expert opinion (consensus) .
In our work place according to the clinical background we start with iv Pulse methyl prednisolone 500 mg /day for (3-5)days tell the biopsy result appear, if the diagnosis is confirmed then start Plasmapharesis (1.5 volume on alternative days followed by IVIG 100 mg /kg after each session .
3- Adjustment of IS according to the drug level.
4- Monitoring of graft function .
Diagnosis is AMR WITH C4D-ve due to de novo DSA , supported by the presence of peritubular lymphocytes’ infiltration.
Management
combination i.v methylprednisolone at dose 300 to 500 mg daily for 5 days followed by rapid oral prednisone
plasmapheresis is performed daily.
Or every other day for a maximum of six sessions or until creatinine is decreased 20 to 30% of baseline
IVG 100 mg/kg after each session of PE
Rituximab single dose375 MG/M2
Augment the immunosuppression therapy
What is your diagnosis?
This is 31-year –old recipient has a new DSA post-transplantation, C4d was negative and his biopsy shows lymphocyte infiltration in the glomeruli and the peritubular capillaries→He is C4d negative ABMR.
What is your management plan?
-IV pulse methylprednisolone(500 mg/day for 3doses)
-Plasma exchange
-IV immunoglobulin
-Follow-up DSA level, monitor TAC level,and RFT.
-If there is no improvement, add rituximab.
Oh my god
Will you give all of this Ben?
Do you have Bortozomib and Ecluzumab available in Kenya?
Agree with the diagnosis, C4d negative AMR
Thank prof, I have indicated between brackets what we can do ; they are essentially ; Methyl pred, plasmapherssi, rituximab.
This patient developed posttransplant DSA with significant MFI level associated with graft biopsy shows glomerular and peritubular capillaries infiltration with negative c4d staining, so it is mostly C4d negative ABMR
Treatment plan
1- Pulse methyl prednisolone 500 mg /day for (3-5)days
2- Plasmapharesis (1-1.5 volume on alternative days followed by IVIG 100 mg /kg after each session .
3- Augment IS level.
4- Monitoring DSA, graft function , if no improvement consider rituximab
Excellent Fatima
The right diagnosis and treatment are based on the available resources. Well done
This patient has circulating DSA, in addition to the histological features of glomerulitis (g) and peritubular capillaritis (ptc), suggesting a diagnosis of C4d-negative AMR
Treatment:
Currently, there are no approved therapies and treatment guidelines are based on low-level evidence.
For Active AMR with De novo DSA: Optimize baseline immunosuppression (eg, add steroids if on a steroid-free regimen) (1C) Evaluate and manage non-adherence. Plasmapheresis and IVIG (3C), Rituximab (3C) can be used.
For Chronic AMR with De novo DSA use IVIG (3C)
Eculizumab results in terminal complement blockade as a monoclonal antibody targeting C5 was used in the case series with some success.
A large retrospective series suggests that T-cell depletion using Antithymocyte Globulin in combination with steroids has no effect on the outcome in vascular AMR.
There are several case series of surgical splenectomy, splenic embolization, and splenic radiation being used as a salvage procedure for severe early AMR.
References
Schinstock CA, Mannon RB, Budde K, et al. Recommended Treatment for Antibody-mediated Rejection After Kidney Transplantation: The 2019 Expert Consensus From the Transplantion Society Working Group. Transplantation. 2020 May;104(5):911-922.
Dear all; good responses to such a tricky question
Time of rejection not mentioned clearly in scenario ,I think we depend mainly on clinical manifestation ,chronicity and activity pathological score to tailor our treatment plan for example if high activity index in biopsy and marked suddenly deranged RFT after 5 years without marked chronic changes we will start with strong medications according to type of rejection and in contrast if there is chronic /in active rejection with gradual worsening RFT after 3years so we not be aggressive in treatment
If we still doubt , we can stain with CD68 if came predominantly positive its mainly pure ABMR) if withCD3 positive so may be mixed TCMR.
1.The history didn’t talk about time per se but my understanding is we are still in early post-transplant period and more over the biopsy is favoring acute rather than chronic processes. The other things is rejection occur at anytime and this is why the terms acute or chronic are not necessarily reflecting time lines. ABMR is a dilemma and some times you don’t know what to do with the patient.
2.ATG is a reasonable option, in fact no thing called pure ABMR and there is always cellular elements(Help provided by CD4 cells to B cells) and therefore you steriods or ATG depending how severe the situation.
3.It will not change the management much
4.For me the diagnosis is clear, I wont do anything further and managment remains the same.
The time of rejection not mentioned but being noncomplement mediated AMR usually occure latemore than 6 months due to the memory B cells re-call immune activation in the presence of denovo DSA while complement mediated rejctionoccure early post transplant in first 3 months alone or in combination withTCMR. the type of lymphocytes includes NKcells , machrophage , neutrophiles ( APC). so treatment will be dircted to remove AB by plasmaphersis and IVIGs and B cells depleting agent like rituximab,,memory cells have low thershold of activation in presensitized patients even with low level of DSA and ususally resistant to CTLA4ig Belatocepts as the recall-alloimmune response is not depened on costimulatory pathway(1) . so no role of belatocepts or ATG in currnet scenario .
we can ask for IHC staining for B cells markers like CD20 ,B-lymphocyte associated immunoglobulins in the graft biopsy(2).
1- Hand book of kidney transplant 6th edition .
2-New insights into the development of B cell responses: Implications for solid organ transplantation,Hum Immunol. 2019 June ; 80(6): 378–384.
Time was NOT clearly stated, but C4d-negative may occur early or late.
Although it may be less severe than C4d-positive AMR, BUT IF NOT TREATED IT CAN STILL LEAD TO TRANSPLANT GLOMERULOPATHY.
Both have similar frquencies of concurrent TCMR.
And both can occur early or late
Biopsy analysis will suffice
I don,t know what role could peipheral lymphocyte analysis would play.
-Time of rejection not clearly mentioned in scenario which is important to chick chronicity and plan of management.
– ATG is indicated in TCMR especially if there is steroid resistance or high Banff classification.
– CBC differential in peripheral blood as thereis association between ABMR and neutrophilia.