EARLY ACUTE REJECTION
A.FALSE Acute rejection episodes differ in their impact on graft survival depending on severity ,time of occurrence ,number of episodes and degree of recovery of function after treatment ;return to base line having no negative impact
B.TRUE TCMR without marked histological abnormalities with steroid response has good outcome
C.FALSE Functional recovery rate in that stage is high and is associated with good graft outcome
D.F.AMR is accompanied by poor graft survival due to DSA and possibility of recurrence and development of chronic allograft dysfunction associated with chronic rejection
E.FALSE Early acute rejection occurs in first 6 months.
REFERENCES
Uptodate ,kidney transplantation in adults : clinical features and diagnosis of acute renal allograft function,2021
Lammarche,C et al,cellular rejection treatment according to Bannf score in kidney transplantationrecipients ;A systematic review, Transplant Direct,2016:2:e115
Koo,HE,et al,Impact of early andlate acute rejection on graft survival in renal transplantation ,Kidney Res Clin Proced,2015,Sept;4(3):160-164
Rehab Fahmy
3 years ago
acute rejection can occur early in transplantation in patients with DR mismatches and in patients with DGF
It carries high risk of graft loss (due to recurrrent rejection and development of CAN
Ben Lomatayo
3 years ago
A. False, not always
B. True, if responded well, no further issues
C. False, the clinical significance nay not be clear
D. False , high chance of graft loss
E. False, 3 to 6 months
Ben Lomatayo
3 years ago
Early acute rejection is generally better than late rejection because in the early phase the immune system is not yet fully prime and there are few numbers of APCs, especially dendritic cells.
Advances in immunosuppressive therapy contributed to a significant reduction in T cell-mediated rejection to 10% to 20 %.
< 10% of the kidney transplants recipients developed rejection after the first year of transplantation. This is called late rejection and it is often associated with non-adherence
A single event of rejection decreases 5-year graft survival by < 10 %
Rejection appears as a sudden rise in Cr, or biopsy finding in cases of protocol biopsies, and DGF
Reference; Oxford Hand Book of Nephrology & Hypertension, second edition
Wessam Moustafa
3 years ago
The incidence of acute rejection has dramatically fallen in the previous years due to advances in immunosuppressive medication whether as induction or maintenance regimen .
Early acute rejection was found to be associated with HLA-DR mismatch and delayed graft function and lead to graft failure due to chronic allograft nephropathy and recurrent acute rejection.
Early episodes of acute rejection may also have consequences for the patients and their grafts beyond the 1st 6 months after transplantation. Greater histological severity of cellular acute rejection has been associated with inferior death-censored graft survival.
Vascular acute rejection is strongly associated with premature graft failure and the development of chronic allograft nephropathy. ABMR particularly when vascular involvement is evident, represents a high risk of graft failure in the coming 5 years.
Recipients with early acute rejection also more likely to die from cardiovascular diseases or cancer.
Reference:
Clayton Ph.A., McDonald S.P.,Russ G.R., Chadban S.J. Long-Term Outcomes after Acute Rejection in Kidney Transplant Recipients: An ANZDATA Analysis. JASN( 2019)
Ahmed Ziada
3 years ago
Acute rejection within the first six months after transplantation mostly T cell mediated a single episode of rejection reduces five years graft survival by 10% the greater the number of episodes the worse the outcome of transplantation
Ahmed Omran
3 years ago
AR is acute worsening of allograft function manifested by tissue diagnosis.
2 forms are there
-TCMR
-Active ABMR or mixed form
CNI and antiproliferative agents significantly improved incidence of AR.
Vascular AR is associated with early graft failure and premature CAN in protocol biopsies. ABMR has the high risk of graft failure over following five years.
AR episode is high risk factor for graft loss .which is increased by severity of rejection ,late development, non recovery to baseline function .It was suggested that late AR has worse effect on long term graft survival. Increased graft loss following AR is related to extent of graft injury that leads to CAN .The associated DSA can lead to subsequent AMR.
REFERENCES
WU,K et al: The severity of acute cellular rejection defined by Banff classification is associated with kidney allograft outcomes,Transplantion97:1146-1154,2014
Fatima AlTaher
3 years ago
Acute rejection is a major risk factor for graft loss depending on
· timing of occurrence (Late acute rejection has more negative impact on graft survival).
· severity of the rejection episode (depending on banuff classification .
· Number of rejection episodes : as recurrent episode are associated with poorer out come
· triggering factor ( infection , non adherence to IS)
· response to treatment (where the graft function improved to base line or not)
So early AR is a significant risk factor for graft loss compared to no rejection
1- Jalalzadeh, M., Mousavinasab, N., Peyrovi, S., & Ghadiani, M. H. (2015). The impact of acute rejection in kidney transplantation on long-term allograft and patient outcome. Nephro-urology monthly, 7(1), e24439. https://doi.org/10.5812/numonthly.24439 2- Koo, E. H., Jang, H. R., Lee, J. E., Park, J. B., Kim, S. J., Kim, D. J., Kim, Y. G., Oh, H. Y., & Huh, W. (2015). The impact of early and late acute rejection on graft survival in renal transplantation. Kidney research and clinical practice, 34(3), 160–164. https://doi.org/10.1016/j.krcp.2015.06.003
AMAL Anan
3 years ago
BANFF Classification Of Rejection:
AMAL Anan
3 years ago
AR was defined clinically by an acute deterioration in allograft function and confirmed with tissue diagnosis. Banff borderline AR was not considered as an AR episode. Graft failure was defined as transplant nephrectomy, retransplantation, or return to long-term dialysis. Delayed graft function was defined as the need for dialysis in the 1st week.
We found that EAR was associated with male sex, HLA mismatch, and older donor. LAR was associated with young recipient age and positive PRA. HLA mismatches are well-known risk factors for AR.
We found that EAR was associated with male sex, HLA mismatch, and older donor. LAR was associated with young recipient age and positive PRA. HLA mismatches are well-known risk factors for AR.
References:
1. Joseph JT, Kingsmore DB, Junor BJ, Briggs JD, Mun Woo Y, Jaques BC, Hamilton DN, Jardine AG, Jindal RM. The impact of late acute rejection after cadaveric kidney transplantation. Clin Transplant. 2001;15:221–227.
2. Opelz G, Dohler B. Influence of time of rejection on long-term graft survival in renal transplantation. Transplantation. 2008;85:661–666.
3. Sijpkens YW, Doxiadis II, Mallat MJ, de Fijter JW, Bruijn JA, Claas FH, Paul LC. Early versus late acute rejection episodes in renal transplantation. Transplantation. 2003;75:204–208.
Nasrin Esfandiar
3 years ago
Early acute rejection especially acute T cell rejection if treated early and completely (steroid -responsive) could have a good prognosis. But if there is delay in diagnosis and treatment, they will affect negatively graft survival.
Abdullah Raoof
3 years ago
It has been demonstrated that an acute rejection(AR) episode is amajor risk factor of graft loss.
However,notall rejection episodes have the same effect
factors that determine the impact are
Severity of rejection,as described using the Banff system,
timing of rejectionas early(EAR) or latea cute rejection(LAR),
whether the allograft recovers to the baseline function after rejection.
Several studies have evaluated the difference between EARand LAR interms of impact on long-term graft survival.Somestudies have suggested that LAR has apoorer effect on long-term graft survival than EAR . It has been proposed that
differences in immunologic activity and triggering factors such as infection or nonadherence to immunosuppressive medication may be the reasons for these distinctions .
in one study both EAR and LAR . has a negative impact on graft survival . both EAR and LAR were significant risk factors for graft failure compared with the no AR group.
Recently,ElTersetal [6] showed that early acute cellular rejection was not a single acute event but triggered apersis- tent alloimmune response that might result in long-term graft
injury and graft loss years after the acute event
Many studies have been conducted to explore whether the timing of AR affects graft survival.The majority of these studies reported that LAR was correlated with poor long-
term graft survival [1–3]. However,reports about the impact of EAR are inconsistent. We thought that there as on for variable results might be that each study used different
methods and populations ,with the cut off for EAR being particularly variable.Some studies used a3-month cut off to divide EAR and LAR [1,3].
refference :
1.Eun Hee Koo, Hye Ryoun Jang,Jung Eun Lee, Jae Berm Park, Sung-Joo Kim,Dae Joong Kim, Yoon-Goo Kim,Ha Young Oh, and Wooseong Huh. The impact of early and late acute rejection on graft survival in renal transplantation. Kidney Res Clin Pract. 2015 Sep; 34(3): 160–164. 2. Joseph JT,Kingsmore DB,JunorBJ,BriggsJD,MunWooY,Jaques BC, Hamilton DN, Jardine AG,Jindal RM:The impact of late acute rejection after cadaveric kidney transplantation. Clin Transplant 15:221–227,2001
Ahmed mehlis
3 years ago
AR, regardless of its timing, significantly worsened graft survival. Treatments to reduce the incidence of AR and improve prognosis are needed.
But late acute rejection (after 1 year of transplantation)has poor prognosis than EAR .
Dear All Answer the following question with a justification of your answer (not more than 50 words): Early acute rejection
A. Always associated with reduced graft survival (False) B. Steroid-sensitive ACR is not associated with poor graft outcome (True) C. Mild rejection (ACR Banff 1/2A) is associated with poor graft outcome. (False) D. Antibody-mediated rejection is not associated with poor graft outcomes if treated. (False) E. It happened any time within the first year of transplantation (False).
JUSTIFICATION: A- EARs are usually TCMR, low grade mild AMR, subclinical detected on protocol biopsy, usually of good outcome because of advances in IS drugs, monitoring DSA, regular follow up and protocol biopsy. B-True. C- mild ACR are usually steroid sensitive with good graft outcome. D-AMR is usually complicated with recurrent, chronic ABMR, and graft loss. E- EARs are within first 3-6 months post-transplant.
Hinda Hassan
3 years ago
A. Wrong , it is associated reduced graft survival in 86%
B. True
C. Wrong
D. Wrong as it affect the graft survival .
E. Wrong, it is defined as rejection within the first six months after transplant
Esmat MD
3 years ago
Answer the following question with a justification of your answer (not more than 50 words):Early acute rejection A. Always associated with reduced graft survival false B. Steroid-sensitive ACR is not associated with poor graft outcome True C. Mild rejection (ACR Banff 1/2A) is associated with poor graft outcome False D. Antibody-mediated rejection is not associated with poor graft outcomes if treated successfully True E. It happened any time within the first year of transplantation True
In addition to the intensification of maintenance immunosuppression therapy, pulse glucocorticoids are usually the only additional treatment for type IA or IB, and the expected reversal rate for the first episode of acute TCMR is 60-70 %.
By 10 years after kidney transplant, up to 25% have developed de novo DSA (dnDSA). Thus, it is not surprising that AMR is the most common cause of allograft failure.
Even among patients who recover, acute rejection episodes can have a negative impact on long-term graft survival.
Acute rejection is a strong risk factor for the development of chronic allograft nephropathy. The incidence of CAN is <1 percent in patients who have had no episodes of acute rejection.
Clinical phenotypes of AMR
Early posttransplant (<30 days) active AMR
In patients with preexisting DSA, active AMR can occur within 30 days after transplantation. In general, this form of AMR is uncommon. With prompt diagnosis and treatment, patients can recover allograft function and histological features of active AMR frequently resolve completely. In other cases, the histological features of active AMR persist and chronic active AMR, allograft dysfunction, and ultimate allograft failure ensues.
Early posttransplant active ABMR presents with an abrupt allograft dysfunction in patients with DSA or immunologic amnestic response to alloantigens at the time of transplantation.
Late (>30 Days) posttransplant AMR with preexisting DSA
Many patients with preexisting DSA can develop an indolent and progressive form of AMR that is usually initially detected on a surveillance biopsy (in the setting of stable function) or on a for-cause biopsy for mild allograft dysfunction. At diagnosis, there is often minimal if any reduction in glomerular filtration rate (GFR) or proteinuria even when mild chronic features are present. Overtime, however, the GFR declines and the patient becomes proteinuric.
Late (>30 days) AMR associated with dnDSA
In the current era of sensitive DSA testing and a general avoidance of preexisting DSA, the most common form of AMR is associated with dnDSA.
dnDSA is a new DSA detected after >3 months posttransplant 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.
AMR with dnDSA is associated with inferior allograft survival when compared with AMR from preexisting DSA.
The risk of TG is higher in those with multiple episodes of acute rejection, late rejection episodes (occurring >6 months after transplantation), and increased severity of the acute rejection episodes.
Early AMR is usually C4d positive and has DSAs against either HLA class I or class II.
Fortunately, allograft function can be restored through rapid diagnosis and treatment, and the histological features of active ABMR are often completely resolved.
Immunoglobulin G (IgG) subclasses are also related to the phenotypes of ABMR. Acute ABMR is mainly accompanied by IgG3 DSA, whereas subclinical ABMR is accompanied by IgG4. Subclass IgG3 is associated with a shorter time to graft failure and C4d deposition in allograft peritubular capillaries. Subclass IgG4 is associated with a slower progression to graft failure and a lower incidence of C4d deposition. But IgG4 is associated with transplant glomerulopathy and interstitial fibrosis/tubular atrophy. T cell-mediated rejection may be more often encountered in ABMR with dnDSA than ABMR with preformed DSA.
Min Young Kim and Daniel C. Brennan. Therapies for Chronic Allograft Rejection. Frontiers in pharmacology. April 2021. Volume 12
Mahmud Islam
3 years ago
acute graft rejection early post-transplantation could be either T cell or antibody-mediated (ABMR/TCMR) but both may coexist. acute early rejection is mostly due to preformed donor-specific antibodies and mostly aggressive entailing aggressive treatment with steroids and in case of being antibody-mediated by removal of antibodies by plasmapheresis and or addition of IVIG . mostly it leaves chronic changes. this will increase with each episode. fibrosis and tubular atrophy will lead eventually to graft failure
Asmaa Khudhur
3 years ago
Long-term survival of renal allograft is significantly associated with AREs
Patients’ survival was significantly affected by the combination of DGF and rejection
AREs had no adverse effect on long-term renal graft function if they were successfully treated
The main factors for a more successful long-term allograft outcome are immunologic such as low rate of ARE and advancement of immunosuppressant agents
EARs were not as significant risk factors of chronic graft loss compared with LARs
Some previous studies argued that EARs are as much of a risk factor as LARs in chronic graft loss
However, EAR does not appear to be a risk factor of long-term successful results, it is still a major complication that increases hospital costs
Studies have shown that the number of ARE has negative impact on graft survival
Furthermore, recipients with one ARE have been found to show better survival rates than those with two or more episodes of rejection
many factors affect patient-graft survival
gender of recipients and age of donor had some influence
the timing of an acute rejection episode was associated with the success rate of patient-graft survival. Late acute rejection appears to reduce long-term allograft survival rate
Reference:
The Impact of Acute Rejection in Kidney Transplantation on Long-Term Allograft and Patient Outcome
AUTHORS
Mojgan Jalalzadeh 1 , Nouraddin Mousavinasab 2 , Said Peyrovi 3 , Mohammad Hassan Ghadiani 4 , *
Mahmoud Hamada
3 years ago
Early acute rejection episodes have been reduced significantly with the introduction of CNIs in immunosuppressive protocols. In the study by OPTN, the incidence reduced from 10% in 2010 to 8% in 2017 (1)
DSA positivity, HLA mismatch, DGF, pediatric recipients, and prolonged cold ischemia time all are associated with more early acute rejection.
Acute rejection is associated with negative graft survival. However, if properly treated and graft was maintained, it has no negative outcome on prolonged graft survival (2). References: Hart A, Smith JM, Skeans MA, Gustafson SK, Wilk AR, Castro S, Foutz J, Wainright JL, Snyder JJ, Kasiske BL, Israni AK. OPTN/SRTR 2018 Annual Data Report: Kidney. Am J Transplant. 2020 Jan;20 Suppl s1:20-130. doi: 10.1111/ajt.15672. PMID: 31898417.
Madden RL, Mulhern JG, Benedetto BJ, O’Shea MH, Germain MJ, Braden GL, O’Shaughnessy J, Lipkowitz GS. Completely reversed acute rejection is not a significant risk factor for the development of chronic rejection in renal allograft recipients. Transpl Int. 2000;13(5):344-50. doi: 10.1007/s001470050712. PMID: 11052270.
Wael Hassan
3 years ago
Acute rejection impact on graft survival
Sure it will affect on it and reduce its survival specially if not treated early
But some studies show that Acute rejection in first 6 months if treated fast and cured rapidly not affect the graft survival
MICHAEL Farag
3 years ago
Acute renal allograft rejection is a major cause of allograft dysfunction. Some kidneys do not regain function even with maximal antirejection therapy.
Even among patients who recover, acute rejection episodes can have a negative impact on long-term graft survival. Acute rejection is a major predictor of interstitial fibrosis/tubular atrophy (IF/TA), formerly called chronic allograft nephropathy, which is responsible for most death-censored graft loss after the first year posttransplant
Acute rejection episodes are generally associated with a reduction in long-term allograft survival, although not all rejection episodes have the same impact on long-term graft function.
Factors such as timing of rejection, severity and number of acute rejections, and degree of recovery of function after treatment all affect the long-term outcome . If renal function returns to baseline, acute rejection does not necessarily cause irreparable damage or impact long-term graft survival
Tahani Hadi
3 years ago
Acute graft rejection has negative impact and direct effect on graft survival and may cause prolonge renal impairment regardless the usage of medical treatment ,acute rejection is the major cause of interstitial fibrosis and tubular atrophy both lead to graft nephropathy
It’s important to evaluate pre and post transplant risk factors of acute rejection and identify it’s type and severity this happen mainly by doing graft biopsy which give idea about the proper management.
There are multiple risk factors for AR like patients with pre transplant DSA ,age ,race and subsequent transplants ,regarding post transplant risk this is related mainly to the immunosuppression regimen like using ATG in induction with TAC and MMF with or without steroid give better outcome regarding AR .
The prognosis and the effect of rejection on graft outcome depend on type and severity of the acute rejection
Reference
-Evaluation and treatment of acute rejection in kidney allograft. (2020).CJASN,15(3),430,438.
-kidney transplantation principles and practice (8ed. ).(2020).Philadilphia:STUART J.KNECHTLE ,LORNA P.MARSON,SIR PETERJ.MORRIS
fakhriya Alalawi
3 years ago
Both acute rejection (AR) and allograft functions early post-transplantation correlate with long-term graft survival. A study done by Cosio FG in 1997, included 843 adult recipients of first cadaveric renal grafts, studied for a minimum of 3.5 years, found graft survival was significantly worse in patients with AR and an elevated SCr (6mo) compared with patients who had AR but low SCr(6mo) and patients without AR but with an elevated SCr(6mo) (P<0.0001), hence concluded that the SCr (10d) concentration had correlated for graft prognosis. On the other hand, several other studies have suggested that late acute rejection (LAR) has a poorer effect on long-term graft survival than EAR.
Jalalzadeh M et al, in 2015, found that late acute rejection (LAR) had a negative impact on long-term renal allograft survival (had lower 5-year graft survival rate) compared to early AR, and the risk of chronic graft dysfunction increased in patients with a history of LAR.LAR was more commonly associated with males (P = 0.001) and donors’ age (P = 0.0002). While Koo EH et al, in a study of 709 patients, 198 (30%) had biopsy-proven AR [EAR=152 patients (77%); LAR=46 patients (23%)]. The 5-year graft survival rates were 97%, 89%, and 85% for patients with no AR, EAR, and LAR, respectively. These differences were significant (P<0.001 for both). In time-dependent Cox regression analysis, EAR (hazards ratio, 3.37; 95% confidence interval, 1.90–5.99) and LAR (hazards ratio, 5.32; 95% confidence interval, 2.65–10.69) were significantly related to graft failure.
References:
1. Cosio FG, Pelletier RP, Falkenhain ME, Henry ML, Elkhammas EA, Davies EA, Bumgardner GL, Ferguson RM. Impact of acute rejection and early allograft function on renal allograft survival. Transplantation. 1997 Jun 15;63(11):1611-5.
2. Koo EH, Jang HR, Lee JE, Park JB, Kim SJ, Kim DJ, Kim YG, Oh HY, Huh W. The impact of early and late acute rejection on graft survival in renal transplantation. Kidney Res Clin Pract. 2015 Sep;34(3):160-4. doi: 10.1016/j.krcp.2015.06.003. Epub 2015 Jul 26.
3. Jalalzadeh M, Mousavinasab N, Peyrovi S, Ghadiani MH. The impact of acute rejection in kidney transplantation on long-term allograft and patient outcome. Nephrourol Mon. 2015 Jan 20;7(1):e24439. doi: 10.5812/numonthly.24439.
Weam Elnazer
3 years ago
A. Always associated with reduced graft survival: false
the kind of rejection matters, since steroid-responsive acute T cell-mediated rejection, as well as mild cellular rejection, will have no effect on the outcome of the transplantation.
B. Steroid-sensitive ACR is not associated with poor graft outcomes. True, C. Mild rejection (ACR Banff 1/2A) is associated with poor graft outcomes. false. D. Antibody-mediated rejection is not associated with poor graft outcomes if treated.false
Mueller A, Schnuelle P, Waldherr R, et al. Impact of the Banff ’97 classification for histological diagnosis of rejection on clinical outcome and renal function parameters after kidney transplantation. Transplantation. 2000;69:1123–1127. 3
E. It happened any time within the first year of transplantation. false within the first 6 months, but some trials used the cutoff 1 year between early and late rejection
(The impact of early and late acute rejection on graft survival in renal transplantation Eun Hee Koo, Hye Ryoun Jang , Jung Eun Lee , Jae Berm Park , Sung-Joo Kim, Dae Joong Kim, Yoon-Goo Kim, Ha Young Oh , Wooseong Huh)
Nandita Sugumar
3 years ago
Acute rejection, irrespective of timing since transplantation, has poor rates of graft survival. Late acute rejection has a poorer effect on long term graft survival than early acute rejection.
Early acute rejection, as well as late acute rejection, have negative effects on long term graft survival. THis can be a significant factor in the development of graft failure.
According to El Ters et al, “ Early acute cellular rejection is not a single acute event, but triggers a persistent alloimmune response that might lead to long term graft injury and graft loss years after the acute event. “
MOst studies that explore whether the timing of AR affects graft survival rates have reported that LAR is more commonly seen to be related to poor long term graft survival. EAR link to graft failure does not seem to be reported in a consistent manner.
EAR incidence was found to be linked to factors such as
Male gender
HLA mismatch
Older donor
On the other hand, LAR was found to be linked to young recipient age, positive PRA. This could be because of non-compliance or increased immune responsiveness.
Graft biopsy, either clinical or protocol biopsy, is the gold standard to diagnose EAR, although limitations include the test being invasive, and failure in predicting AR.
Ref:
Koo EH, Jang HR, Lee JE, Park JB, Kim SJ, Kim DJ, Kim YG, Oh HY, Huh W. The impact of early and late acute rejection on graft survival in renal transplantation. Kidney Res Clin Pract. 2015 Sep;34(3):160-4. doi: 10.1016/j.krcp.2015.06.003. Epub 2015 Jul 26. PMID: 26484041; PMCID: PMC4608868.
Ibrahim Omar
3 years ago
acute rejection in the 1st 6 months post-transplantation with result in acute graft dysfunction/failure. it needs an early and effective treatment to restore the kidney function.
if acute rejection is not adequately treated, it may result in incopmlete recovery or even unrecovery and possible loss of graft function.
even adequately treated acute rejection can involve some serious side effects related to the invasive nature of renal biopsy and also the more intensive immunosuppression and possible flare of latent infections…. etc. graft survival may be affected.
finally, even successfully treated recurrent acute rejection can affect the long term graft survival.
Mahmoud Rabie
3 years ago
Early acute rejection that occurs in the first 6 months post transplantation has a poor effect on graft survival either acute TCMR or acute AMR. The incidence of early acute rejection has decreased markedly due to the advances in immunosuppressive medications. The effect of late acute rejection is poorer on graft survival than early acute rejection. Early acute rejection may be associated with HLA-DR mismatches. Also inadequate immunosuppressive medications at the peak time of immune activity has a great role in early acute rejection.
effect of early acute rejection (within the first 6 months after transplantation) on graft survival?
Early acute rejection occurs in 1st 6m post transplant. Usually mild pure TCMR or mild ABMR because
1) improvement of AB screening pre-transplant
2)recent immune suppression medications specially after the era of CNI.
3) usually detect early
4) patient usually at high side of immune suppression medications.
Some studies showed 10y graft survival in early acute rejection vs late acute rejection (84 %to40% respectively)
Reference
1.Eun Hee Koo, Hye Ryoun Jang,Jung Eun Lee, Jae Berm Park, Sung-Joo Kim,Dae Joong Kim, Yoon-Goo Kim,Ha Young Oh, and Wooseong Huh. The impact of early and late acute rejection on graft survival in renal transplantation. Kidney Res Clin Pract. 2015 Sep; 34(3): 160–164.
2. Deborah Zimmerman, Andrew A. House, S. Joseph Kim, Ronald A. Booth, Tinghua Zhang, Tim Ramsay, and Greg Knoll . The Risk of Acute Rejection Following Kidney Transplant by 25-Hydroxyvitamin D and 1,25-Dihydroxyvitamin D Status: A Prospective Cohort Study. Can J Kidney Health Dis. 2017; 4: 2054358117699822.
Abdulrahman Ishag
3 years ago
The risks of both death with function and death- censored graft failure is attributed to cardiovascular disease and cancer. Lower eGFR and albuminuria are recognized as independent risk factors for all-cause and cardiovascular mortality consequent to AR. The intensity of immunosuppression may affect both cardiovascular risk, through mechanisms including development of new-onset diabetes, hypertension, dyslipidemia, renal impairment and proteinuria .
Recently AR ,that occur within first 6 months after kidney transplantation is found to be associated with significant increases in risk of both death with function and graft loss due to CAN, the leading causes of transplant failure in the current era. The associations noted were strongest for those with AMR and for those where initial therapy failed to enable return to baseline serum creatinine. Despite the decline in both the incidence of AR and the incidence of early graft loss directly caused by AR, these data highlight the importance of AR as a pivotal early event after transplantation with long-lasting con- sequences.
Referance;
Organ Procurement and Transplantation Network (OPTN) and Scien-
tific Registry of Transplant Recipients: (SRTR). OPTN/SRTR 2011 Annual
Data Report, Rockville, MD, Department of Health and Human Ser-
vices, Health Resources and Services Administration, Healthcare Sys-
tems Bureau, Division of Transplantation, 2012
Australia and New Zealand Dialysis and Transplant Registry: 39th An-
nual Report, Chapter 8, Transplantation. Australia and New Zealand
Dialysis and Transplant Registry, Adelaide, Australia, 2016
McDonald S, Russ G, Campbell S, Chadban S: Kidney transplant re-
jection in Australia and New Zealand: Relationships between rejection
and graft outcome. Am J Transplant 7: 1201–1208, 2007
Meier-Kriesche HU, Schold JD, Srinivas TR, Kaplan B: Lack of improve-
ment in renal allograft survival despite a marked decrease in acute re-
jection rates over the most recent era. Am J Transplant 4: 378–383, 2004
OʼConnell PJ, Kuypers DR, Mannon RB, Abecassis M, Chadban SJ, Gill
JS, et al.: Clinical trials for immunosuppression in transplantation:
case for reform and change in direction. Transplantation 101: 1527–
1534, 201
Mohammed Sobair
3 years ago
Acute rejection episode associated with increased risks of longer-term graft failure
and death, particularly death from cardiovascular disease and cancer.
Factors affect survival:
Timing (EAR VERSUS LAR), severity and return of graft to function affect long-term graft
outcome. Immunologic activity and triggering factors such as infection or nonadherence
The complication associated with acute rejection is graft failure if not treated appropriately and timely fashion. Even after the treatment, there is an
association of poor graft survival after each episode of rejection.
Reference:
Ruchi H. Naik; Saed H. Shawar. renal Transplantation Rejection. StatPearls
,July 25, 2021.
Doaa Elwasly
3 years ago
Early acute rejection
A. Always associated with reduced graft survival —-False
B. Steroid-sensitive ACR is not associated with poor graft outcome—True
C. Mild rejection (ACR Banff 1/2A) is associated with poor graft outcome—–False
D. Antibody-mediated rejection is not associated with poor graft outcomes if treated—True
E. It happened any time within the first year of transplantation—Fasle
Development of immunosuppressive protocols decreased the rate of acute rejection and lowered the rate of chronic rejection and improve long-term graft survival.
The Banff classification for AMR identifing and demonstrating pathologic features and diagnostic criteria to better understand
Treatment of AMR has produced a variety of results, some of them suboptimal, affecting the development of standardized protocols
Newer therapies are promising,
Thanks, Doaa
AMR is always associated with poor graft outcomes even with effective treatment. It represents a severe rejection
Doaa Elwasly
3 years ago
The decrease in acute rejection incidence is rendered to marked improvements in 1-year graft survival, after the introduction of cyclosporine and T cell–depleting induction .
It was categorised as steroid responsive and steroid non responsive ,
It is classified as T cell mediated or antibody mediated.
Acute rejection risk depends on immunologic risk at the pretransplantion period depending on pretransplant DSA and HLA A/B/DR mismatch being the main factor as well as number of transplants, recipient’s age and race.
In post transplantation period acute rejection risk is dependent upon immunosuppression regimen and exposure.
The gold standard for diagnosing acute rejection in kidney transplant recipients is tissue biopsy. Allograft histology is interpreted using the Banff classification of kidney allograft pathology
· Banff grade 1a with moderate lymphocytic infiltration of the tubules
· Banff grade 1b with severe lymphocytic interstitial infiltration and tubulitis .
· Banff grade 2a with arterial intimal lymphocytic infiltration .
· Peritubular lymphocytic infiltration characteristic of antibody-mediated rejection.
· Positive C4d staining of the peritubular capillaries by immunohistochemistry.
the Banff classification required three features for diagnosis:
(1) active tissue injury,
(2) immunohistologic evidence of peritubular capillary complement split-product C4d deposition,
(3) circulating DSA.
The revised 2013 Banff criteria for antibody-mediated rejection diagnosis removed the requirement for C4d detection and included the evidence of current/recent antibody interaction with vascular endothelium,” which may include either
(1) positive C4d staining,
(2) at least moderate microvascular inflammation, or
(3) increased expression of endothelial gene transcripts .
The most recent Banff studies showed a lack of DSA with significant microvascular inflammation and low false positive rate of C4d staining, and removed the need of documented circulating DSA with positive C4d staining and microvascular inflammation
Studies of urine and blood biomarkers, such as CXCL9, CXCL10, granzyme B, perforin, and Fas ligand, have shown variable efficacy for identifying acute rejection, differentiating T cell–mediated rejection from antibody-mediated rejection
Decreased urinary miR-210 levels have been associated with T cell–mediated rejection and subsequent 1-year GFR decline
donor-derived cellfree DNA (cf-DNA) profiling has been used in the noninvasive diagnosis of antibody-mediated rejection,
noninvasive biomarkers have failed to completely replace tissue diagnosis
Reference
Cooper JM.Evaluation and Treatment of Acute Rejection in Kidney Allografts .CJASN March 2020, 15 (3) 430-438
Jamila Elamouri
3 years ago
Early acute rejection: A- Always associated with reduced graft survival. (F) B- Steroid-sensitive ACR is not associated with poor graft outcome. (T) C- Mild rejection (ACR Baff 1/2A) is associated with poor graft outcome. (F) D- Antibody-mediated rejection is not associated with poor graft outcomes if treated. (F) E- It happened any time within the first year of transplantation. (F)
Not all rejection attacks should be assumed equal, and the pathologic processes of the rejection episode, the severity, and the response to therapy (recovery of the graft function to baseline) expect the long-term outcome. T-cell–mediated rejection is an important cause of early allograft failure, but is a less common cause of late allograft failure except in cases of drug non-adherence. Acute rejections that occur late (after the first 3 months) is more predictive of chronic allograft failure than those that occur during the first 3 months; rejections that occur very early and are reversed may have little or no effect on the outcome. More severe rejection and multiple rejection episodes are more likely to predict late allograft failure.
Hi Dr Jamila, I want to know the effect of early acute rejection (within the first 6 months after transplantation) on graft survival. Please provide literature evidence that supports your answer
EAR is a major barrier to improving long-term graft survival. Graft biopsy, either clinical biopsy or protocol biopsy, consedered the gold standard for diagnosing EAR. For the prevention and early detection of EAR, an immunologic monitoring method developed that can stratify risky patient to predict AR and choose immunosuppressive protocol.
Refere
Eun Hee Koo et AL, The impact of early and late acute rejection on graft survival in renal transplantation,
Kidney Research and Clinical Practice,
Volume 34, Issue 3,
2015,
Pages 160-164,
ISSN 2211-9132, https://doi.org/10.1016/j.krcp.2015.06.003.
(https://www.sciencedirect.com/science/article/pii/S2211913215300036)
Reem Younis
3 years ago
-Rate of acute rejection (AR) and graft survival have steadily improved over time but still acute rejection is a major risk factor of graft loss and not all rejection episodes have the same effect. Long-term graft outcome affect by:
1. severity of rejection.
2. Timing of rejection as early or late acute rejection.
3. Recovery of allograft to the baseline function after rejection.1
-AR is a risk factor for chronic rejection.
–AR classifies into the following :
1. Antibody-mediated rejection: It is usually demonstrated evidence of circulating DSA and immunological evidence of antibody-mediated injuries to the kidney(glomerulitis, peritubular capillaritis)
2. Acute T-cell mediated rejection: it is characterized by lymphocytic infiltration of tubules, interstitium, and sometimes the arterial intima.
–Predisposing factors for acute rejection include the number of HLA mismatches, delayed graft function, deceased donor, repeat transplant, PRA level, race, female gender.2
-Some studies have suggested that late acute rejection has a poorer effect on long-term graft survival than early rejection, and recent studies showed that early rejection was not the cause of graft failure.
-A cohort of 654 patients who underwent cadaveric renal transplants (1983-1997) that functioned for more than 6 months was studied. In 384 0f 654 transplant recipients, one or more treated ARs were documented, the last AR occurred in 297 within 3 months and 87 after 3months. Ten-year graft survival rates censored for causes of graft loss other than chronic rejection were 94%( patient without AR),86 % (patients with early AR), and 45% (patient with late AR).3
-Late AR has a serious impact on long-term graft survival and is associated with MHC class I incompatibility while early AR is correlated with HLA-DR mismatches and has a better prognosis.3 References:
1.Eun Hee Koo, Hye Ryoun Jang,Jung Eun Lee, Jae Berm Park, Sung-Joo Kim,Dae Joong Kim, Yoon-Goo Kim,Ha Young Oh, and Wooseong Huh. The impact of early and late acute rejection on graft survival in renal transplantation. Kidney Res Clin Pract. 2015 Sep; 34(3): 160–164.
2. Deborah Zimmerman, Andrew A. House, S. Joseph Kim, Ronald A. Booth, Tinghua Zhang, Tim Ramsay, and Greg Knoll . The Risk of Acute Rejection Following Kidney Transplant by 25-Hydroxyvitamin D and 1,25-Dihydroxyvitamin D Status: A Prospective Cohort Study. Can J Kidney Health Dis. 2017; 4: 2054358117699822.
3. Yvo W J Sijpkens , I.I Doxiadis,Kamel Mallat ,Johan W de Fijter. Early versus late acute rejection episodes in renal transplantation .Reseach gate.February 2003Transplantation 75(2):204-8
Weam Elnazer
3 years ago
Late ARE has a detrimental impact on long-term graft survival and is associated with MHC class I incompatibility, whereas early ARE is correlated with HLA-DR mismatches and has a better prognosis. These data are consistent with the role of direct and indirect allorecognition in the pathophysiology of early and late ARE, respectively.
early TCMR (even borderline or subclinical) is linked to ongoing inflammation (i), the subsequent development of moderate/severe graft interstitial fibrosis (GIF), transplant glomerulopathy (TG) and a higher rate of de novo Class II DSA. Indeed, those patients with early TCMR whose pathology evolves on the follow-up biopsy have an increased incidence of alloimmune mediated graft loss associated with TG and GIF.
early TCMR leads to the development of de novo DSA, which in turn could result in AMR and the evolution of TG.
acute and chronic; early and late; clinical and subclinical; and classify rejection as TCMR and AMR, its role is to protect the host at all costs and by whatever mechanisms are available.
We suggest that the immune system provides an integrated response to achieve allograft rejection with TCMR and AMR being either linked through time or coexisting. If such is the case, then it behoves us to keep T cells in the forefront, alongside B cells/plasma cells and DSA, in order to improve long-term outcomes.
Professor Ahmed Halawa
Admin
3 years ago
Dear All Answer the following question with a justification of your answer (not more than 50 words):Early acute rejection
A. Always associated with reduced graft survival
B. Steroid-sensitive ACR is not associated with poor graft outcome
C. Mild rejection (ACR Banff 1/2A) is associated with poor graft outcome
D. Antibody-mediated rejection is not associated with poor graft outcomes if treated E. It happened any time within the first year of transplantation
EAR occur in first 6 months post transplantation, not all rejection episodes had same effect on graft outcome, the outcome determined by severity of rejection episode& response to treatment & if full recovery accomplished. So if the episode was mild & full recovery accomplished after treatment the outcome will be good. Mild acute cellular rejection constitute about half of all ACR, & it respond to pulse steroids ( 70% of it is steroid responder) with good graft outcome.
A. Always associated with reduced graft survival- F
Episodes of EAR was reported by several studies to be more benign than episodes of LAR this may be explained by the lower incidence and severity of ABMR which is associated with lower graft survival, Moreover attacks of TCMR are usually mild responding well to corticosteroids
This may be explained by the following :
Advances in detection of preformed antibodies
Screening of DSA usually done in all patients in the early post transplant period so rejection can be managed early
Advances in immunosuppression including induction therapy
Strict follow up in the early post transplant period, including some times protocol biopsy
When compared to LAR there is lower probability of either planned subtherapeutic immunosuppression (due to malignancy, infection) , conversion to CNI free or CS free protocols or non compliance on immunosuppressive medication which constitute high risk factors for ABMR which is more aggressive and associated more with lower graft survival when compared to TCMR
So … early AR episodes are usually mild ABMR, TCMR or subclinical rejection
B. Steroid-sensitive ACR is not associated with poor graft outcome T
C. Mild rejection (ACR Banff 1/2A) is associated with poor graft outcome F
Mild cell mediated rejection Banff 1/2A is associated with good graft outcome
Banff 1A is usually steroid sensitive and pulse cortecosteroids and augmentation of immunosuppression usually reverse rejection
Banff 2A has good response to corticosteroids but may need addition of ATG to reverse rejection
Any histologic severity greater than Banff 1 A (except 2A) was associated with poor prognosis (1)
D. Antibody-mediated rejection is not associated with poor graft outcomes if treated F
Acute and chronic ABMR are associated with poor outcomes even if treated , Moreover patients with acute ABMR are at increased risk of recurrent rejection , chronic ABMR and graft loss [2].
E. It happened any time within the first year of transplantation F
Early AR indicates occurrence of AR in the first 3 months, or 6 months after transplantation
REFERANCES
1. Wu K, Budde K, Schmidt D, et al. The Relationship of the Severity and Category of Acute Rejection With Intimal Arteritis Defined in Banff Classification to Clinical Outcomes. Transplantation 2015; 99:e105.
2. Wiebe C, Gibson IW, Blydt-Hansen TD, et al. Evolution and clinical pathologic correlations of de novo donor-specific HLA antibody post kidney transplant. Am J Transplant 2012; 12:1157.
Acute rejection may cause a negative impact on allograft survival except in conditions when it is of a mild degree and there is full recovery of kidney functions (1).
The development of subclinical and clinical DSA is associated with decreased long term allograft survival as illustrated in the attached graph (2).
A is false ; For kidney and liver grafts, steroid-sensitive ACR has little impact on ultimate outcome.
B is true ; lack of effect of T cell–mediated rejection on long-term outcome has been well documented
( Halloran PReeve JP, Pereira AB, et al. Antibody-mediated rejection, T cell-mediated rejection, and the injury-repair response: New insights from the Genome Canada studies of kidney transplant biopsies. Kidney Int 2014; 85: 258–264.)
C is false. Banff group 1A,1B &2A are responding to therapy,so when treated properly in time will not affect the graft outcome.
{ However, the complete functional response rates of Banff grade 1 pooled and grade 1B separately (44-73%) overlapped with those of Banff grade 2A (52-80%), whereas lower figures were reported for Banff grade 2B rejections (10%)} ((Transplant Direct. 2016 Dec; 2(12): e115. Published online 2016 Nov 15. doi: 10.1097/TXD.0000000000000626 PMCID: PMC5142362 PMID: 27990480))
D is True. treated AMR with good response rate is associated with high survival rate of the graft.
In a pilot study of 7 AMR patients treated using PLEX and IVIG at 100 mg/kg/d for 3 days, then 3 times per week for 2-4 weeks, then rituximab 500 mg/m2 for 1 dose if AMR was ongoing at week 4, Mulley et al found 100% graft survival at 21-month follow-up.60 As mentioned earlier, Lefaucheur et al conducted a retrospective study of 12 AMR patients compared with historic control (IVIG). The treatment group received PLEX and IVIG 100 mg/kg × 4 doses, then IVIG 2 g/kg every 3 weeks × 4 doses, and rituximab 375 mg/m2/week × 2 doses. Graft survival was 91.7% in the treatment group vs 50% in the control group. Kaposztas et al performed a retrospective study of 54 AMR patients compared with historic control (PLEX and IVIG).61 The treatment group received rituximab 500 mg/m2, PLEX, and IVIG 500 mg/kg if an immunoglobulin G deficiency was noticed. Graft survival was 90% in the treatment group vs 60% in the control group. {Antibody-Mediated Rejection: A Review
Jorge Carlos Garces, Sixto Giusti, Catherine Staffeld-Coit, Humberto Bohorquez, Ari J. Cohen, George E. Loss
Ochsner J. 2017 Spring; 17(1): 46–55. PMCID: PMC5349636}
E is false. early acute rejection is referred to time period of the first 3 to 6 months post-transplantation.
Early acute rejection
A. Always associated with reduced graft survival…F usually respond to treatment with full recovery if treated early
B. Steroid-sensitive ACR is not associated with poor graft outcome…F
Associated with good graft outcomes
C. Mild rejection (ACR Banff 1/2A) is associated with poor graft outcome..F
Usually respond to steroids with good graft survival
D. Antibody-mediated rejection is not associated with poor graft outcomes if treated…F
acute ABMR associated with poor graft survival with risk of recurrence, chronic ABMR and TG
E. It happened any time within the first year of transplantation..F
Early mean T 1st 6m post transplant
A- False, EAR not always associated with poor graft outcome it depends on the type and the severity of AR plus the response to the therapy if mild form of AR with complete response usually has favorable graft outcome (1)
B-True, mild TCMR with no significant histological changes and steroid responsive has favor outcome(3).
C-True, early TCMR may trigger persistent alloimmune response with denovo DSA expression and increase the risk of AMR (2).
D- FLASE AMR associated with poor graft survival as its associated with DSAs, Denovo DSA and risk of recurrence and progress to chronic allograft dysfunction with Chronic rejection.
E-False, early acute rejection limited to the first 6 months (3).
References:
1-The impact of early and late acute rejection on graft survival in renal transplantation
Eun Hee Koo,1 Hye Ryoun Jang,1 Jung Eun Lee,1 Jae Berm Park,2 Sung-Joo Kim,2 Dae Joong Kim,1 Yoon-Goo Kim,1 Ha Young Oh,1 and Wooseong Huh1, Kidney Res Clin Pract. 2015 Sep; 34(3): 160–164.
2-Impact of acute rejection episodes on long-term renal allograft survival:
Jianyong Wu 1, Jianghua Chen, Yimin Wang, Jianguo Zhang, Zong Zhu, Zhangfei Shou, Suya Wang, Ping Zhang, Hongfeng Huang, Qiang HeChin Med J (Engl). 2003 Nov;116(11):1741-5.
3-up to date ,medicine ,kidney transplantation in adult: clinical features and diagnosis of acute renal allograft rejection , 2021.
Answer the following question with a justification of your answer (not more than 50 words): Early acute rejection
A. Always associated with reduced graft survival
B. Steroid-sensitive ACR is not associated with poor graft outcome
C. Mild rejection (ACR Banff 1/2A) is associated with poor graft outcome
D. Antibody-mediated rejection is not associated with poor graft outcomes if treated
E. It happened any time within the first year of transplantation
Answer:
A. False- early acute rejection is not always associated with reduced graft function.
a. Cellular rejection banff 1A, 1B and borderline without involving vascular has good prognosis
b. One episode of acute rejection which resolves with treatment to pre-rejection creatinine has good graft survival compared with no AR
B. True- steroid sensitive ACR is usually did not differ in term of graft survival compared with whom did not had AR
C. False -Mild rejection (ACR Banff 1/2A) usually respond well to treatment and did not associated with poor graft function
D. False-Antibody mediated rejection has been associated with increased risk of graft loss and effective therapy has been lacking
E. False -early acute rejection has been classified according 3-6months or usually within 6 months
References
1. Clayton, P., McDonald, S., Russ, G. and Chadban, S., 2019. Long-Term Outcomes after Acute Rejection in Kidney Transplant Recipients: An ANZDATA Analysis. Journal of the American Society of Nephrology, 30(9), pp.1697-1707.
2. El Ters, M., Grande, J., Keddis, M., Rodrigo, E., Chopra, B., Dean, P., Stegall, M. and Cosio, F., 2013. Kidney Allograft Survival After Acute Rejection, the Value of Follow-Up Biopsies. American Journal of Transplantation, 13(9), pp.2334-2341.
3. Sellarés, J., de Freitas, D., Mengel, M., Reeve, J., Einecke, G., Sis, B., Hidalgo, L., Famulski, K., Matas, A. and Halloran, P., 2011. Understanding the Causes of Kidney Transplant Failure: The Dominant Role of Antibody-Mediated Rejection and Nonadherence. American Journal of Transplantation, 12(2), pp.388-399.
4. Cooper, J., 2020. Evaluation and Treatment of Acute Rejection in Kidney Allografts. Clinical Journal of the American Society of Nephrology, 15(3), pp.430-438.
Always associated with reduced graft survival. False ,, it depends on the type of rejection as steroid responsive acute T cell mediated rejection will not affect graft outcome and also mild cellular rejection.
Steroid-sensitive ACR is not associated with poor graft outcome. True ,, thisformof rejection does not affect graft survival.
Mild rejection (ACR Banff 1/2A) is associated with poor graft outcome. False ,, mild form of rejection is associated with good graft outcome.
Antibody-mediated rejection is not associated with poor graft outcomes if treated. False ,, even with treatment ABMR associated with lower graft outcome due to the complex ABMR phenotypes.
It happened any time within the first year of transplantation. False ,, it happened within the first six months post transplant
A : FALSE
B : TRUE
C : FALSE
D : FALSE
E : FALSE
Early detection and identifying the type of rejection with proper management give good result regarding graft function and survival ,graft rejection is divided into hyperacute,acute and chronic rejection.
Acute rejection occurs within first 6 months post transplant with multiple causes like cellular, numeral and CNI toxicity and ATN ,AMR has poor prognosis even with proper treatment.
A. Always associated with reduced graft survival
False
As single episode of cellular rejection with no vascular component which respond well to treatment have graft survival rate to 5 years as those without rejection
B. Steroid-sensitive ACR is not associated with poor graft outcome
True
As cellular rejection that respond well to treatment is not associated with worse graft outcome
C. Mild rejection (ACR Banff 1/2A) is associated with poor graft outcome
False
As severe grade of rejection is associated with more severe graft loss
D. Antibody-mediated rejection is not associated with poor graft outcomes if treated
False
As AMR significantly impact the graft survival even if treated
E. It happened any time within the first year of transplantation
False
early acute rejection is rejection within 3-6 months post transplant
McDonald, S., Russ, G., Campbell, S. and Chadban, S., 2007. Kidney transplant rejection in Australia and New Zealand: relationships between rejection and graft outcome. American journal of transplantation, 7(5), pp.1201-1208.
Clayton, P.A., McDonald, S.P., Russ, G.R. and Chadban, S.J., 2019. Long-term outcomes after acute rejection in kidney transplant recipients: an ANZDATA analysis. Journal of the American Society of Nephrology, 30(9), pp.1697-1707.
Loheac C, Aubert O, Assayag M, et al. Thymoglobulin induction decreases risk of ABMR and death in kidney recipients. Transplantation. 2018;102:S401.
A. Always associated with reduced graft survival False
Not always , according to the type and severity and if diagnosed early and treated promptly associated with good outcome
B. Steroid-sensitive ACR is not associated with poor graft outcome True
C. Mild rejection (ACR Banff 1/2A) is associated with poor graft outcome False
It’s associated with good graft survival
D. Antibody-mediated rejection is not associated with poor graft outcomes if treated True
E. It happened any time within the first year of transplantation False
It occurs during the first 3-6 months posttransplantation
A-always associated with reduced graft survival ? TRUE
Recently AR ,that occur within first 6 months after kidney transplantation is found to be associated with significant increases in risk of both death with function and graft loss due to CAN, the leading causes of transplant failure in the current era. The associations noted were strongest for those with AMR and for those where initial therapy failed to enable return to baseline serum creatinine. Despite the decline in both the incidence of AR and the incidence of early graft loss directly caused by AR, these data highlight the importance of AR as a pivotal early event after transplantation with long-lasting con- sequences.
Australia and New Zealand Dialysis and Transplant Registry: 39th An- nual Report, Chapter 8, Transplantation. Australia and New Zealand Dialysis and Transplant Registry, Adelaide, Australia, 2016
B- steroid sensitive ACR is not associated with poor graft out come ? TRUE
Steroid sensitive ACR found to be associated with better graft outcome . The response to high-dose corticosteroid therapy for the treatment of acute renal allograft rejection correlates with the expression level and characteristics of T cells and macrophages infiltrating into the renal allograft. These findings indicate that steroid resistance resides in specific cell populations and is not a feature of all lymphocytes.
J. Galon, D. Franchimont, N. Hiroi, G. Frey, A. Boettner, M. Ehrhart-Bornstein, et al. Gene profiling reveals unknown enhancing and suppressive actions of glucocorticoids on immune cells
FASEB J., 16 (1) (2002 Jan), pp. 61-71
C-mild rejection is associated with poor graft outcome ? TRUE
All types of ACR affect long-term graft survival. Vascular or late ACR predict poorer graft survival; the extent of tubulointerstitial inflammation (TI) is of no prognostic significance for vascular rejection.
The severity of acute cellular rejection defined by Banff classification is associated with kidney allograft outcomes2014 Jun 15;97(11):1146-54. doi: 10.1097/01.TP.0000441094.32217.052014 Jun 15;97(11):1146-54. doi: 10.1097/01.TP.0000441094.32217.05.
D- antibody-mediated rejection is not associated with poor graft outcome ,if treated? False
AMR treatment reduced biopsy-associated and serological markers of AMR, but did not affect DSA-DQ.
de Sousa MV, Gonçalez AC, de Lima Zollner R, Mazzali M. Ann Transplant. 2020 Nov 17;25:e925488. doi: 10.12659/AOT.925488.
E- it happened any time within the first year of transplantation ? FALSE
ACR , is defined as rejection ,that occur within first 6 months after kidney transplantation .
Organ Procurement and Transplantation Network (OPTN) and Scien- tific Registry of Transplant Recipients: (SRTR). OPTN/SRTR 2011 Annual Data Report, Rockville, MD, Department of Health and Human Ser-
vices, Health Resources and Services Administration, Healthcare Sys- tems Bureau, Division of Transplantation, 2012
A. Always associated with reduced graft survival B. Steroid-sensitive ACR is not associated with poor graft outcome C. Mild rejection (ACR Banff 1/2A) is associated with poor graft outcome D. Antibody-mediated rejection is not associated with poor graft outcomes if treated E. It happened any time within the first year of transplantation
True: B,D False: A, C, E
A. Always associated with reduced graft survival
False: If early acute rejection is mild ACR Banff I/IIa, it has excellent response to treatment with no significant adverse effect on graft survival. (1)
B. Steroid-sensitive ACR is not associated with poor graft outcome
True: Mild rejection, Banff I/IIa are usually steroid sensitive, and have excellent graft prognosis. (1)
C. Mild rejection (ACR Banff 1/2A) is associated with poor graft outcome
False: The functional reversibility rates of Banff I/IIa are high and those of higher stages are low. Hence Banff I/IIa are associated with good graft outcome. (1)
D. Antibody-mediated rejection is not associated with poor graft outcomes if treated
True: Early AMR, if diagnosed and treated timely, may lead to complete reversal of clinical and histological dysfunction. But if not treated, would lead to chronic ABMR and graft loss. In contrast, late AMR is associated with poor graft outcomes, even if treated timely. (2)
E. It happened any time within the first year of transplantation
False: Early acute rejection is defined differently by different authors, but mostly as the rejection taking place in first 3 to 6 months post transplant
References:
1) Lamarche C, Cote JM, Senecal L, et al. Efficacy of Acute Cellular Rejection Treatment According to Banff Score in Kidney Transplant Recipients: A Systematic Review. Transplant Direct 2016;2:e115.
2) Schinstock CA, Manno RB, Budde K, et al. Recommended Treatment for Antibody-mediated Rejection After Kidney Transplantation: The 2019 Expert Consensus From the Transplantation Society Working Group. Transplantation 2020;104:911-922.
Acute rejection is classified into humoral and cellular although both T and B cells are involved in both types of rejections.
Acute rejection happens any time within the first year of transplantation, but more frequently in the first few months. Acute antibody mediated rejection is always associated with reduced graft survival as the presence of DSA alone even without histologic confirmation of acute rejection is associated with adverse renal outcomes. However mild cellular rejection (ACR Banff 1/2A) due to under-immunosuppression, if managed appropriately, carries no poor prognosis. Steroid-sensitive ACR is not associated with poor graft outcome
A. Always associated with reduced graft
survival. False
early ARE has a better prognosis. The graft survival after early ARE is not severely compromised
B. Steroid-sensitive ACR is not associated with poor graft outcome. true
C. Mild rejection (ACR Banff 1/2A) is associated with poor graft outcome. false
Acute vascular rejection is an adverse prognostic feature compared with tubulointerstitial rejection
D. Antibody-mediated rejection is not associated with poor graft outcomes if treated..false
Antibody-mediated rejection (AMR), particularly when vascular involvement is evident, have a high risk of graft failure over the ensuing 5 years.
E. It happened any time within the first year of transplantation. false
An early ARE was defined as an ARE occurring within 3 to 6 months post transplantation
1-YVO W. J. SIJPKENS. EARLY VERSUS LATE ACUTE REJECTION EPISODES IN RENAL TRANSPLANTATION. Vol. 75, 204–208, No. 2, January 27, 2003
Printed in U.S.A.
2-Philip A. Clayton,1,2,3 Stephen P. McDonald,1,2,3 Graeme R. Russ,1,2,3 and Steven J. Chadban1,4,5. Long-Term Outcomes after Acute Rejection in Kidney Transplant Recipients: An ANZDATA Analysis. JASN 30: 1697–1707, 2019
3-Eun Hee Koo 1, Hye Ryoun Jang 1, The impact of early and late acute rejection on graft survival in renal transplantation. 2015. The Korean Society of Nephrology. Published by Elsevier.
Dear All Answer the following question with a justification of your answer (not more than 50 words):Early acute rejection A. Always associated with reduced graft survival graft outcome is better in non rejection state than in the presence of any rejection and it is better in EAR than LAR . THE PROGNOSIS depend on
severity of AR
Timing of rejection
response to is medication.
return of graft function to baseline after treatment .
B. Steroid-sensitive ACR is not associated with poor graft outcome — true
T cell-mediated rejection (TCMR) which respond to is , has little effect on outcomes
C. Mild rejection (ACR Banff 1/2A) is associated with poor graft outcome —- false
mild ACR ( not involving vessels ) has good prognosis , but prognosis is worsen as the sevesrity of vascular injury is increased
D. Antibody-mediated rejection is not associated with poor graft outcomes if treated false
AMR usually associated with bad outcome and usually end by graft failure because on chronic allograft rejection . Up to 8-year posttransplantation, death-censored graft survival (DCGS) rates of control, borderline, TCMR I, and TCMR II/III groups were 97.6%, 93.3%, 79.6%, and 73.6% (log rank test, P<0.001); the control group had significantly higher DCGS rate than the three ACR groups (each pairwise comparison yields P<0.05). The DCGS rate of late ACR was significantly lower compared with early ACR (63.6% vs. 87.4%, P<0.001). Intimal arteritis (Banff v-lesion) was an independent histologic risk factor correlated with long-term graft loss regardless of the timing of ACR. The v-lesions with minimal or high-grade tubulitis displayed similar graft survival (72.7% vs. 72.9%, P=0.96).
E. It happened any time within the first year of transplantation true
reffrences
Wu K, Budde K, Schmidt D, et al. The Relationship of the Severity and Category of Acute Rejection With Intimal Arteritis Defined in Banff Classification to Clinical Outcomes. Transplantation 2015; 99:e105.
Eun Hee Koo,1 Hye Ryoun Jang,1 Jung Eun Lee,1 Jae Berm Park,2 Sung-Joo Kim,2 Dae Joong Kim,1 Yoon-Goo Kim,1 Ha Young Oh,1 and Wooseong Huh1,The impact of early and late acute rejection on graft survival in renal transplantation Kidney Res Clin Pract. 2015 Sep; 34(3): 160–164
A- False.
According to BANFF classification if mild it will respond to treatment.
B-True.
It associated with good graft outcomes.
C-False.
Respond to treatment and associated with good graft outcomes.
D-False.
It associated with recurrence or chronic rejection.
5-False.
Early means first 6 month post- transplantation.
Dalia Eltahir
3 years ago
. An acute rejection (AR) episode is a major risk factor of graft loss. However, not all rejection episodes have the same effect. Severity of rejection histologic severity of cellular AR has been associated with inferior death-censored graft survival. Vascular AR in particular has been strongly associated with premature graft failure and histologically with premature development of chronic allograft nephropathy (CAN) . Antibody-mediated rejection (AMR), particularly when there is vascular involvement carry a high risk of graft failure over the 5 years. Timing of rejection as early (EAR) or late acute rejection (LAR), late acute rejections are associated with worse prognosis and inferior graft survival. Development of de novo DSA, non adherence or suboptimal immunosuppression and recurrent acute rejection episodes are important risk factors for LAR. Close monitoring of these patiens, making an early diagnosis and intensive treatment of LAR may help improve graft survival and long term outcome . Allograft recovers to the baseline function after rejection are known to affect the long-term graft outcome . Treatment for AR with high-dose steroids and/or lymphocyte-depleting antibodies lead to increased risk of sepsis and cancer, potentially leading to death with a functioning graft.Inferior graft function, proteinuria, and increased immunosuppression may also heighten cardiovascular risk, thereby predisposing affected recipients to cardiovascular morbidity and mortality.
Acute rejection is still a major complication after renal transplantation. The overall incidence of acute rejection varies between 10% and 50% within the first 6 months
depending on the degree of human leukocyte antigen (HLA) matching and treatment used for immunosuppression .
Not all acute rejection episodes (AREs) result in an adverse outcome.
Therefore, it is important to define what kind of ARE is associated with late graft loss
. Acute vascular rejection is an adverse prognostic feature compared with
tubulointerstitial rejection
The occurrence of both interstitial and vascular rejection is associated with HLA-DR mismatches and delayed graft function, but the risk of developing vascular rejection is decreased in patients receiving cyclosporine compared with those receiving azathioprine
A severe ARE exerts a more detrimental effect on long-term outcome than an ARE with complete functional recovery
. No single factor could differentiate between the two entities, but
Recipients with repeated AREs have lower graft survival rates than those with no or only one episode
Timing of the ARE has an impact on long-term outcome. An ARE within the first 3 months may have no effect on chronic rejection ,whereas an ARE occurring after 3 or 6 months confers the greatest risk
Reference
YVO W. J. SIJPKENS. EARLY VERSUS LATE ACUTE REJECTION EPISODES IN RENAL TRANSPLANTATION. Vol. 75, 204–208, No. 2, January 27, 2003
Printed in U.S.A.
Hinda Hassan
3 years ago
early acute rejection decrese graft survival and more graft loss. In a cohort of cadaveric renal transplants patients ,Ten-year graft survival rates censored for causes of graft loss other than chronic rejection were 94%, 86%, and 45% for patients without acute rejection, with early acute rejection, and with late acute rejection, respectively. 1 In a 6 year study acute rejection occurred in 34 cases . 12 out of 34 had early acute rejection. The graft survival is shorter in the fourth year 87% compared to those without rejection 94%. Graft loss is more 1/12 compared with those without rejection6/114 but less than late2 In a small study comparing between re-transplant and first transplant, the rate of acute AMR was similar between both groups but the acute TCMR was more in re-transplant group. Interestingly, the one year survival and graft survival were comparable3 A large study of 13614 recipients confirmed the association between acute rejection within 6 months post transplant and graft loss attributed to chronic allograft , death with a functioning graft and with death due to cardiovascular disease and cancer , even after subtyping according to biopsy-proven, antibody-mediated, or vascular rejection, or response to treatment , same results were obtained4
1-Sijpkens YW, Doxiadis II, Mallat MJ, de Fijter JW, Bruijn JA, Claas FH, Paul LC. Early versus late acute rejection episodes in renal transplantation. Transplantation. 2003 Jan 27;75(2):204-8. doi: 10.1097/01.TP.0000041722.34000.21. PMID: 12548124. 2-Esra Baskin, Asli Kantar, Kaan Gulleroglu, Esra Ozmen, Handan Ozdemir, Mahir Kirnap, Gokhan Moray, Mehmet Haberal, SP873 EFFECTS OF LATE ACUTE REJECTION ON GRAFT SURVIVAL AND OUTCOME IN PEDIATRIC RENAL TRANSPLANT RECIPIENTS, Nephrology Dialysis Transplantation, Volume 30, Issue suppl_3, May 2015, Page iii665, https://doi.org/10.1093/ndt/gfv203.11 3- Lan Zhu et al ,Patterns of Early Rejection in Renal Retransplantation: A Single-Center Experience Journal of Immunology Research, 2016, 2697860 – December 2016 ,https://doi.org/10.1155/2016/26978604-Philip A. Clayton, Stephen P. McDonald, Graeme R. Russ, Steven J. Chadban ,Long-Term Outcomes after Acute Rejection in Kidney Transplant Recipients: An ANZDATA Analysis ,JASN Sep 2019, 30 (9) 1697-1707; DOI: 10.1681/ASN.2018111101
saja Mohammed
3 years ago
In recent decades there is significant reduction in the incidence of AR in particular TCMR due to better immunologic matching of donor and recipients, more potent induction as well as maintenance immunosuppressive agents, however acute rejection in the first 6 months still can impact the graft survivalespcialy in sensitazed recpients and this depending on many factors like the time ,type of rejection and severity of AR based on Banff histological classification.
The type of acute rejection:
1- pure acute T -cell mediated rejection, (TCMR) which limited to tubular inflammatory cells infiltration (Lymphocytes T-cells,)tubulitis and interstitial mononuclear cells infiltration with or without vascular injury ( endothelitis ), sever TCMR with vascular injury even with in 6 months can impact the graft survival , Steroid responsive TCMR usually have favor prognosis and outcome especially in the absence of significant chronic histological findings like IFTA, vascular intimal sclerosis, arteriolar hyaline thickening or frank necrosis those with vascular injury and steroid nonresponsive preferred to be treated with ATGs with augmentation of maintenance IS (tacrolimus, MMF, steroid).
2-ABMR with typical PTC – C4D staining and peritubular capillaritis (neutrophiles infiltrations), glomerulitis with GC ,also vascular injury with endothelitis plus serological evidence of DSAs, the concept of C4D negative ABMR should be consider in patients with histological finding suggestive of ABMR and positive serology for DSAs, and this can be explained by complement independent binding of DSAs AB to endothelial cells .ABMR may present as only as ATN in the context of acute graft dysfunction, endothelial linear C4D staining is highly suggestive of ABMR, especially in sensitized recipient ,ABMR carry poor prognosis compared to TCMR Graft and patient survival were worse in those who experienced rejection in the first 6 months post-transplant, particularly for those who experienced AMR. P,0.001(3).
3- Mixed type of rejection ,both acute cellular and ABMR can coexist and with vascular injury carry poor prognosis and impact the graft survival even with aggressive treatment, sometimes difficult to differentiate between the ABMR and sever TCMR especially in the presence of ATN with vascular injury (intimal arteritis), ABMR carry the risk of recurrence of rejection and /or progress to chronic graft injury with IFTA and chronic allograft nephropathy (CAN).
other factors that impact the outcome of acute rejection including the DSAs level, type, and the degree of sensitization, also type of donor? DD with EDC, DGF.
One study of 687 transplant recipients at one U.K. center in 1984 to 1996 defined “early” AR as occurring within 90 days of transplantation and “later” AR as any AR event from 91 days out to a maximum of 14 years (7). Five-year graft survival rates were 87% in patients without AR, 63% in those with “early” AR, and 45% in those with “late” AR
increased graft loss risk associated with late AR is likely mediated by multiple factors
late AR is more of AB mediated and carry poor prognosis (1,2) as clinical monitoring is less intense in the later period , patient follow up every 2-3 months so late AR can be diagnosed late with more sever and chronic graft damage and less treatable at time of diagnosis(1).
Type of HLA mismatch:
HLA class II mismatches have been associated with early AR, while class I mismatches have been associated with late AR, suggesting roles of direct and indirect allorecognition pathways in the pathophysiology of early AR and late AR.
References:
1-un-Q, Liu ZH, Ji S, et al. Late and early C4d-positive acute rejection: different clinico-histopathological subentities in renal transplantation. Kidney Int 2006; 70: 377.
2- the Implications of Acute Rejection for Allograft Survival in Contemporary U.S. Kidney Transplantation
Lentine, Krista L.1,5; Gheorghian, Adrian1; Axelrod, David2; Kalsekar, Anu3; L’italien, Gilbert3,4; Schnitzler, Mark A.1
3- up to date, kidney transplant in adult treatment of acuteT cell-mediated (cellular) rejection of renal allograft.
Shereen Yousef
3 years ago
Acute rejection was defined clinically by an acute deterioration in allograft function and confirmed with tissue diagnosis. Banff borderline AR was not considered as an AR episode.
It has been demonstrated that an acute rejection (AR) episode is a major risk factor of graft loss.
Effect of ACUTE REJECTION;
not all rejection episodes have the same effect. Severity of rejection, described using the Banff system, timing of rejection as early (EAR) or late acute rejection (LAR), and whether the allograft recovers to the baseline function after rejection
all these variables affect the long-term graft outcome.
difference between EAR and LAR in impact on long-term graft survival.
Some studies have suggested that LAR has a poorer effect on long-term graft survival than EAR and recent studies showed that EAR was not the cause of graft failure 1.
It has been proposed that differences in immunologic activity and triggering factors such as infection or nonadherence to immunosuppressive medication may be the reasons for these distinctions 1.
A study by Eun Hee et al.on 709 patients Of these, 198 (28%) had biopsy-proven AR, 152 (21%) had EAR, 46 (7%) had LAR, and 511 (72%) did not have a rejection episode.
Allograft failure occurred in 65 patients. The 5-year graft survival rates were 97%, 89%, and 85% for patients with no AR, EAR, and LAR, respectively .
The graft survival rates were not different between the EAR group and LAR group 2.
Recently, El Ters et al showed that early acute cellular rejection was not a single acute event but triggered a persistent alloimmune response that might result in long-term graft injury and graft loss years after the acute event 3.
Acute rejection histologic types are
ABMR OR TCMR or mixed type.
Greater histologic severity of cellular AR has been associated with inferior death-censored graft survival.
Vascular AR in particular has been strongly associated with premature graft failure and histologically with premature development of chronic allograft nephropathy (CAN) in protocol biopsies.
Antibody-mediated rejection (AMR), particularly when vascular involvement is evident, incurs a high risk of graft failure over the ensuing 5 years.
mean serum creatinine at 12 months post-transplant was significantly higher among those with versus without AR suggested a degree of graft injury that may predispose to CAN.
Treatment for AR with high-dose steroids and/or lymphocyte-depleting antibodies incurs an increased risk of sepsis and cancer, potentially leading to death with a functioning graft.
Inferior graft function, proteinuria, and increased immunosuppression may also heighten cardiovascular risk, thereby predisposing affected recipients to cardiovascular morbidity and mortality.
Vascular AR is typically treated more aggressively than nonvascular rejection and may incur greater risks of both permanent graft damage and treatment-emergent adverse effects 4.
In comparison to those with AR without evidence of AMR, those with AMR experienced progressively higher rates of both graft loss and death over time, becoming evident beyond 5 years post-transplant
Lower eGFR and albuminuria are recognized as independent risk factors for all-cause and cardiovascular mortality in the general and kidney transplant populations and both may occur consequent to AR 4.
The intensity of immunosuppression may affect both cardiovascular risk, through mechanisms including development of new-onset diabetes, hypertension, dyslipidemia, renal impairment and proteinuria,and cancer risk.
AR was associated with significant increases in CAN, the leading causes of transplant failure in the current era. The associations noted were strongest for those with AMR and for those where initial therapy failed to enable return to baseline serum creatinine 4.
1 Sellares J, de Freitas DG, Mengel M, Reeve J, Einecke G, Sis B, Hidalgo LG, Famulski K, Matas A, Halloran PF. Understanding the causes of kidney transplant failure: the dominant role of antibody-mediated rejection and nonadherence. Am J Transplant. 2012;12:388–399.
2 Eun Hee Koo, Hye Ryoun Jang,The impact of early and late acute rejection on graft survival in renal transplantation.Kidney Res Clin Pract. 2015 Sep; 34(3): 160–164.
3 El Ters M, Grande JP, Keddis MT, Rodrigo E, Chopra B, Dean PG, Stegall MD, Cosio FG. Kidney allograft survival after acute rejection, the value of follow-up biopsies. Am J Transplant. 2013;13:2334–2341.
4 Philip A. Clayton, Stephen P. McDonald, Graeme R. Russ and Steven J. Chadban.Long-Term Outcomes after Acute Rejection in Kidney Transplant Recipients: An ANZDATA Analysis.JASN September 2019, 30 (9) 1697-1707.
What is the effect of early acute rejection (within the first 6 months after transplantation) on graft survival?
Post renal transplant acute rejection episodes have decreased in current immunosuppressive era. Nonetheless, the effect of these rejections has been shown to reduce long-term graft survival. (1)
Early acute rejection is associated increased risk of recurrent acute rejections and increased risk of graft loss due to chronic allograft nephropathy. (1,2)
Opelz et al, in their study, showed that the risk of graft loss in a patient with acute rejection within first 3 months and 3-6 months post transplant is 35 % and 105% more as compared to someone who did not face any acute rejection episode. (2) This was more pronounced in those who did not respond fully to the treatment of acute rejection.
Tiers at al, in their analysis of graft biopsies, concluded that graft survival was poorer in only those patients with acute rejection who had abnormal histological changes post rejection. (3)
Ragheb et al, in their study showed that acute rejection is associated with poorer graft survival, but there was no difference in graft survival in early and late rejection group. (4)
Jalazadeh et al also showed that acute rejection episodes are associated with poorer graft survival, but more so in patients with late acute rejection. (5)
References:
1) Clayton PA, McDonald SP, Russ GR, et al. Long-Term Outcomes after Acute Rejection in Kidney Transplant Recipients: An ANZDATA Analysis. JASN 2019;30:1697-1707.
2) Opelz G, Dohler B. Influence of Time of Rejection on Long-Term Graft Survival in Renal Transplantation. Transplantation 2008;85:661-666.
3) Tiers ME, Grande JP, Keddis MT, et al. KidneyAllograftSurvivalAfterAcuteRejection,
theValueofFollow-UpBiopsies. Am J Transplant 2013;13:2334-2341.
4) Ragheb A, Kora MAE, Hassan YF, et al. Study of the effect of early and late acute rejection episodes on renal graft survival. J Egypt Soc Nephrol Transplant 2021;21:98-105.
5) Jalazadeh M, Mousavinasab N, Peyrovi S, et al. The Impact of Acute Rejection in Kidney Transplantation on Long-Term Allograft and Patient Outcome. Nephro Urol MOn 2015;7:e24439.
You need to elaborate more on :
type of rejection
predisposing factors related to patient as sensitisation
outcome of the episode
just needs work and relation to practice
Early Acute Rejection may be either T cell mediated rejection, or ABMR or a combination of both.
Early T cell mediated rejection with Banff I/IIa have excellent graft survival usually (due to increased steroid-responsiveness). Higher Banff TCMR have poorer graft survival. Similarly, Early AMR, if treated promptly, has better graft survival; but if not treated, may lead to chronic ABMR and graft loss. (1)
Presence of pre-existing antibodies are responsible for early AMR, hence the role of meticulous pre-transplant evaluation.
Reference: 1) Schinstock CA, Manno RB, Budde K, et al. Recommended Treatment for Antibody-mediated Rejection After Kidney Transplantation: The 2019 Expert Consensus From the Transplantation Society Working Group. Transplantation 2020;104:911-922.
Thanks Amit for your hard work
I will add to Prof Belal question Do you think that all early acute rejection is associated with poor graft survival? What about late acute rejection?
acute late rejection associated with poor outcome as its likely antibody mediated rejection and also due to late recognition with more chronic graft injury and less responsive to treatment.
reference:
the Implications of Acute Rejection for Allograft Survival in Contemporary U.S. Kidney Transplantation
Lentine, Krista L.1,5; Gheorghian, Adrian1; Axelrod, David2; Kalsekar, Anu3; L’italien, Gilbert3,4; Schnitzler, Mark A.1
Do you think that all early acute rejection is associated with poor graft survival?
No.
Early Acute Rejection may be either T cell mediated rejection, or ABMR or a combination of both.
Early T cell mediated rejection with Banff I/IIa have excellent graft survival usually. Higher Banff TCMR have poorer graft survival. Similarly, Early AMR, if treated promptly, has better graft survival; but if not treated, may lead to chronic ABMR and graft loss. (1)
What about late acute rejection?
Late acute rejections are a consequence of under-immunosuppression, non-adherence, infections and formation of de-novo DSAs. These, as compared to early acute rejections have been shown to have poorer graft outcomes and are associated with class I MHC incompatibility.
Reference: 1) Schinstock CA, Manno RB, Budde K, et al. Recommended Treatment for Antibody-mediated Rejection After Kidney Transplantation: The 2019 Expert Consensus From the Transplantation Society Working Group. Transplantation 2020;104:911-922. 2) Sijpkens YW, Doxiadis IIN, Mallat MJK, et al. Early versus late acute rejection episodes in renal transplantation. Transplantation 2003;75:204-208.
Sherif Yusuf
3 years ago
Episodes of acute rejection whether it is early or late are generally associated with poor graft survival but not all episodes are associated with the same impact on the kidney,
This may depend on some factors: [1,2]
Timing of rejection :later onset of rejection (>3 months post transplant) was associated with worse graft outcomes
Severity of rejection
Number of rejection episodes
Degree of recovery of kidney function after treatment
REFERANCES
1. Opelz G, Döhler B, Collaborative Transplant Study Report. Influence of time of rejection on long-term graft survival in renal transplantation. Transplantation 2008; 85:661.
2. Madden RL, Mulhern JG, Benedetto BJ, et al. Completely reversed acute rejection is not a significant risk factor for the development of chronic rejection in renal allograft recipients. Transpl Int 2000; 13:344.
Episodes of EAR was reported by several studies to be more benign than episodes of LAR this may be explained by the lower incidence and severity of ABMR which is associated with lower graft survival, Moreover attacks of TCMR are usually mild responding well to corticosteroids
This may be explained by the following :
Advances in detection of preformed antibodies
Screening of DSA usually done in all patients in the early post transplant period so rejection can be managed early
Advances in immunosuppression including induction therapy
Strict follow up in the early post transplant period, including some times protocol biopsy
When compared to LAR there is lower probability of either planned subtherapeutic immunosuppression (due to malignancy, infection) , conversion to CNI free or CS free protocols or non compliance on immunosuppressive medication which constitute high risk factors for ABMR which is more aggressive and associated more with lower graft survival when compared to TCMR
So … early AR episodes are usually mild ABMR, TCMR or subclinical rejection
Mohamed Fouad
3 years ago
Definition of Acute rejection (AR):
AR defined clinically by an acute deterioration in allograft function and confirmed with tissue diagnosis. There are two principal histologic forms of acute rejection:
–Acute T cell-mediated rejection(TCMR)
-Active (acute) antibody-mediated rejection(ABMR) or mixed form of ABMR and TCMR Banff borderline AR was not considered as an AR episode.
The emergence of calcineurin inhibitors and antiproliferative agents dramatically lowered the incidence of acute rejection.
Vascular AR has been strongly associated with premature graft failure and histologically with premature development of chronic allograft nephropathy (CAN) in subsequent protocol biopsies.
Antibody-mediated rejection (AMR), especially when vascular involvement is evident, carrying a high risk of graft failure over the next 5 years.
Acute rejection (AR) episode is a major risk factor of graft loss. But not all rejection episodes have the same effect it depends on:
Severity of rejection, timing of rejection as early or late acute rejection, and whether the allograft recovers to the baseline function after rejection all these factors can affect the long term graft outcome.
Some studies have suggested that late acute rejection has a poorer effect on long-term graft survival than Early acute rejection. It depends on immunologic activity and triggering factors such as infection or nonadherence to immunosuppressive medication may be the reasons for these differences between EAR and LAR.
The Causes of increased graft loss subsequent to AR may be due to:
-The degree of graft injury that may predispose to chronic allograft nephropathy (CAN) -The cellular AR may be predisposed for donor-specific antibody development and subsequent AMR.
References:
Wu K, Budde K, Lu H, Schmidt D, Liefeldt L, Glander P, et al.: The severity of acute cellular rejection defined by Banff classification is associated with kidney allograft outcomes. Transplantation 97: 1146–1154, 2014
Nankivell BJ, Borrows RJ, Fung CL, O’Connell PJ, Allen RD, Chapman JR: The natural history of chronic allograft nephropathy. N Engl J Med 349: 2326–2333, 2003
I think it is not associated with poor graft prognosis in mild steroid responsive TCMR ,in contrary with vascular rejection which is the severe form and can predispose for donor-specific antibody development and subsequent AMR.
Ban Mezher
3 years ago
The major cause of graft failure is AR, but not every episode of rejection had similar effect on graft. There are several factors increase the risk of AR & subsequently graft injury & loss, these factors include:
severity of rejection
timing of rejection ( early vs late )
degree of recovery from rejection
In general the rejection can occur due to:
sensitization ( high PRA )
type of transplant ( DDT > LDT)
advance age of donor
prolonged cold ischemia time
HLA mismatch
+ve B cell cross match
ABO incompatibility
recipient age ( young > old )
recipient race ( black> white )
DGF
treatment non compliance
previous attack of rejection
inadequate immunosuppression
Several studies show that EAR did not have an impact on graft & patients long term prognosis, but Ei Ters et al report that a single episode of acute cellular rejection can cause persistent allo immune response that may end with graft injury & loss.
There are conflict between the result of studies about the effect of EAR on graft outcome & this variability in results may be due to :
using different methods & population
variable cutoff for EAR ( 3, 6, 12 months )
categorizing of EAR & LAR by onset of first episode of AR
inconsistency of AR definition
Resent studies show that EAR has a sequel reflected on patient & graft outcome beyond first 6 months after transplantation & EAR is associated more with male sex, HLA mismatch & older donor.
References:
Koo E., Jang H., Lee J., et al. The impact of early and late acute rejection on graft survival in renal transplantation. frcp, 2015.
Clayton P., McDonald S., Russ G. et al. Long-Term Outcomes after Acute Rejection in Kidney Transplant Recipients: An ANZDATA Analysis. jasn, 2019; 30: 1697-1707.
What about the the prognosis of early steroid sensitive and mild ACR? Are they associated with poor prognosis?
Mohamad Habli
3 years ago
Over the past 2 decades, the number of acute allograft rejections has declined, in particular after the results of SYMPHONY trial, after which, the maintenance therapy in most transplant centers have been standardized as triple therapy including CNI/MMF/steroids.
Despite that, development of acute rejection carries a significant risk of graft loss during the first year following transplantation. As is acute rejection, subclinical rejection with IF/TA is an independent risk of allograft failure.
The definitions of early and late rejections vary between studies, so the cutoff of 6 months is not standardized. Most of studies report early rejection of days to months in timing, and late more than one year.
Several studies had demonstrated a strong link between early rejection and allograft dysfunction and failure in the subsequent 2–5 years. However, not all rejection episodes have the same allograft outcome. The long term graft outcome is affected by the severity of rejection, clinically and histologically, according to Banff criteria, timing of rejection Early vs Late acute rejection , and whether the allograft recovers to the baseline function after rejection.
In some studies, chronic allograft nephropathy was attributed to the development of early acute rejection. Recipients with early rejection had higher risk to develop cardiovascular complications or cancer. Early rejection is associated with significant long-term effects.
Other studies demonstrated that the occurrence of acute rejection was associated with an increased risk of graft loss after 6 months whereas ,late rejection was associated with higher risk of graft loss. The occurrence of acute rejection is associated with an ongoing increased risk of graft loss, particularly if that episode occurred late or included vascular rejection.
Finally, early and late acute rejections affect long-term graft survival. However most of the studies and most recent showed early rejection had poorer graft survival.
References
-Lefaucheur C, Loupy A, Vernerey D, Duong-Van-Huyen J-P, Suberbielle C, Anglicheau D, et al.: Antibody-mediated vascular rejection of kidney allografts: A population-based study. Lancet 381: 313–319, 2013
-El Ters M, Grande JP, Keddis MT, Rodrigo E, Chopra B, Dean PG, et al.: Kidney allograft survival after acute rejection, the value of follow-up biopsies. Am J Transplant 13: 2334–2341, 2013
-Wu K, Budde K, Lu H, Schmidt D, Liefeldt L, Glander P, et al.: The severity of acute cellular rejection defined by Banff classification is associated with kidney allograft outcomes. Transplantation 97: 1146–1154, 2014.
-Philip A. Clayton, Stephen P. McDonald, Graeme R. Russ, and Steven J. Chadban. Long-Term Outcomes after Acute Rejection in Kidney Transplant Recipients: An ANZDATA Analysis. JASN 30: 1697–1707, 2019
-McDonald S, Russ G, Campbell S, Chadban S: Kidney transplant rejection in Australia and New Zealand: Relationships between rejection and graft outcome. Am J Transplant 7: 1201–1208, 2007
Effect of early acute rejection (within the first 6 months after transplantation) on graft survival:
Advances in immunosuppression after kidney transplantation have decreased the influence of early acute rejection (EAR) on graft survival. Several studies have suggested that late acute rejection (LAR) has a poorer effect on long-term graft survival than EAR.
In a prospective study of 709 patients, 198 (30%) had biopsy-proven AR [EAR=152 patients (77%); LAR=46 patients (23%)]. A total of 65 transplants were lost. The 5-year graft survival rates were 97%, 89%, and 85% for patients with no AR, EAR, and LAR, respectively. These differences were significant (P<0.001 for both by log-rank test). In time-dependent Cox regression analysis, EAR (hazards ratio, 3.37; 95% confidence interval, 1.90–5.99) and LAR (hazards ratio, 5.32; 95% confidence interval, 2.65–10.69) were significantly related to graft failure. When we set LAR as standard and compared it with EAR, there was no statistical difference between EAR and LAR (P=0.21). Kidney Res Clin Pract. 2015 Sep; 34(3): 160–164. Published online 2015 Jul 26. doi: 10.1016/j.krcp.2015.06.003 PMCID: PMC4608868 PMID: 26484041 The impact of early and late acute rejection on graft survival in renal transplantation Eun Hee Koo,1 Hye Ryoun Jang,1 Jung Eun Lee,1 Jae Berm Park,2 Sung-Joo Kim,2 Dae Joong Kim,1 Yoon-Goo Kim,1 Ha Young Oh,1 and Wooseong Huh1
Eun Hee Koo et al Study ; 1/ Effect of early acute rejection (within the first 6 months after transplantation) on graft survival:
The 5-year graft survival rates were 97%, 89%, and 85% for patients with no AR, EAR, and LAR, respectively. The patients with EAR or LAR showed lower graft survival rates than those with no AR (P<0.001 for both by log-rank test).The graft survival rates were not different between the EAR group and LAR group (P=0.22 by log-rank test).
2/ Risk profile of EAR and LAR
In univariable analysis, EAR was related to male sex, HLA mismatch, living donor, and short cold ischemic time.
The variable predictive of LAR was young recipient age and positive PRA.
By multivariable analysis, EAR was related to male sex [odds ratio (OR), 1.89, 95% CI, 1.18–3.00], HLA mismatch (OR, 12.27; 95% CI, 2.46–64.19), and older donor age (OR, 1.02; 95% CI, 1.00–1.04).
LAR was associated with younger recipient age (OR, 0.95; 95% CI, 0.91–0.98) and positive PRA (OR, 2.72; 95% CI, 1.20–10.48).
3/ Graft failure risk factor
Univariable and multivariable Cox regression analyses were used to identify independent variables associated with poor transplant outcomes.
Rejection was regarded as a time-dependent variable.
In univariable analysis, EAR (HR, 3.27; 95% CI, 1.88–5.66), LAR (HR, 5.10; 95% CI, 2.59–10.08), longer dialysis duration (HR, 1.01; 95% CI, 1.00–1.00), and deceased donor (HR, 1.84; 95% CI, 1.02–3.31) were significant risk factors for graft failure.
In multivariable analysis, EAR (HR, 3.37; 95% CI, 1.90–5.99) and LAR (HR, 5.32; 95% CI, 2.65–10.69) were significantly related to graft failure.
When we set LAR as standard and compared it with EAR, there were no statistical difference between EAR and LAR (P = 0.21).
In Eun Hee Koo et al Study ;
EAR, as well as LAR, had negative effects on long-term graft survival.
In a time-dependent Cox regression test to evaluate the risk factors for graft survival, both EAR and LAR were significant risk factors for graft failure compared with the no AR group.
Unlike other studies that showed that EAR was not the cause of graft failure, EAR was a significant risk factor for graft failure in this study.
Recently, El Ters et al showed that early acute cellular rejection was not a single acute event but triggered a persistent alloimmune response that might result in long-term graft injury and graft loss years after the acute event. These findings are consistent with Eun Hee Koo et al Study observation.
Older donor age is known to be related to inflammation in grafts, which is associated with later chronic graft damage.
The association of young recipient age and LAR could be partly explained by noncompliance or increased immune responsiveness.
In this study, male sex was associated with EAR. Evidence for the effect of sex is by no means consistent in many studies.
Thankyou Assafi for the detailed study review on your part can you please mention your own coclusions.
Huda Al-Taee
3 years ago
The incidence of acute rejection has fallen throughout the history of kidney transplantation to around 10-20% as reported by the major registries. Early acute rejection was found to be associated with HLA-DR mismatch and delayed graft function and lead to graft failure due to chronic allograft nephropathy and recurrent acute rejection.
The diagnosis of acute rejection may have short term consequences beyond immediate graft loss. From a patient perspective, anxiety and fear of graft loss, increased tests and cost, follow up frequency, treatment intensity, and risk of side effects including infections and death.
Early episodes of acute rejection may also have consequences for the patients and their grafts beyond the 1st 6 months after transplantation. Greater histological severity of cellular acute rejection has been associated with inferior death-censored graft survival. Vascular acute rejection is strongly associated with premature graft failure and the development of chronic allograft nephropathy. ABMR particularly when vascular involvement is evident, represents a high risk of graft failure in the coming 5 years.
Recipients with early acute rejection also more likely to die from cardiovascular diseases or cancer.
Reference:
Clayton Ph.A., McDonald S.P.,Russ G.R., Chadban S.J. Long-Term Outcomes after Acute Rejection in Kidney Transplant Recipients: An ANZDATA Analysis. JASN( 2019) 30: 1697–1707.
I guess steroid responsive acute cellular rejection
Riham Marzouk
3 years ago
Acute rejection either early or late will affect graft survival.
Definitions:
Acute rejection is defined as acute deterioration of graft function and proved with tissue diagnosis (diagnostic biopsy).
Graft failure defined as graft nephrectomy or retransplantation or return back to chronic dialysis.
DGF is defined as need of dialysis in the 1st week posttransplant.
Graft survival is lower in the patient with acute rejection either early or late than those with the patients with no rejection. Some studies suggested that there is no difference between early and late rejection on graft survival.
There are some factors may be related to early acute rejection (EAR) like HLA mismatch, male sex , living donor, old donor age , short ischemic time. Other factors may be related to late acute rejection (LAR) like young age, and positive PRA.
Both EAR and LAR affect negatively graft survival but no significant difference between both of them.
Some studies found significant impact of EAR on graft survival than LAR, some studies found the contrast.
So, both have a negative impact on survival either early or late.
Eun Hee Koo, Hye Ryoun Jang, Jung Eun Lee, Jae Berm Park, Sung-Joo Kim. The impactof early andlate acute rejectionon graftsurvival in renal transplantation.Kidney Research and Clinical Practice. Volume 34, Issue 3, September 2015, Pages 160-164
Reports about the impact of Early Acute Rejection are inconsistent. The reason for variable results might be that each study used different methods and populations, with the cutoff for EAR being particularly variable. Some studies used a 3-month cutoff to divide EAR and LAR [1,3]. Others used 6- or 12-month cutoffs [7,8]. Most studies categorized EAR and LAR by the onset of the first AR [1,2]. One study used the timing of the last treated AR [3]. Definitions of AR were also inconsistent. Some studies included AR diagnosed using clinical biopsy or using either clinical or protocol biopsy [5]. Others used clinical AR that was not biopsy proven [3,7]. Study populations also differed; some studies selected only deceased-donor kidney transplants [1-3], whereas others enrolled both living- and deceased-donor kidney transplants [5,6].
1. Joseph JT, Kingsmore DB, Junor BJ, Briggs JD, Mun Woo Y, Jaques BC, Hamilton DN, Jardine AG, Jindal RM. The impact of late acute rejection after cadaveric kidney transplantation. Clin Transplant 15:2001;221-227.
2. Opelz G, Dohler B. Influence of time of rejection on long-term graft survival in renal transplantation. Transplantation 85:2008;661-666.
3. Sijpkens YW, Doxiadis II, Mallat MJ, de Fijter JW, Bruijn JA, Claas FH, Paul LC. Early versus late acute rejection episodes in renal transplantation. Transplantation 75:2003;204-208.
4. Famulski KS, Einecke G, Sis B, Mengel M, Hidalgo LG, Kaplan B, Halloran PF. Defining the canonical form of T-cell-mediated rejection in human kidney transplants. Am J Transplant 10:2010;810-820.
5. Sellares J, de Freitas DG, Mengel M, Reeve J, Einecke G, Sis B, Hidalgo LG, Famulski K, Matas A, Halloran PF. Understanding the causes of kidney transplant failure: the dominant role of antibody-mediated rejection and nonadherence. Am J Transplant 12:2012;388-399.
6. El Ters M, Grande JP, Keddis MT, Rodrigo E, Chopra B, Dean PG, Stegall MD, Cosio FG. Kidney allograft survival after acute rejection, the value of follow-up biopsies. Am J Transplant 13:2013;2334-2341.
7. Lentine KL, Gheorghian A, Axelrod D, Kalsekar A, L’Italien G, Schnitzler MA. The implications of acute rejection for allograft survival in contemporary U.S. kidney transplantation. Transplantation 94:2012;369-376.
8. Sun Q, Liu ZH, Ji S, Chen J, Tang Z, Zeng C, Zheng C, Li LS. Late and early C4d-positive acute rejection: different clinico-histopathological subentities in renal transplantation. Kidney Int 70:2006;377-383.
Acute Rejection, regardless of its timing, significantly worsened graft survival. Treatments to reduce the incidence of AR and improve prognosis are needed.
The impact of early and late acute rejection on graft survival in renal transplantation
Eun Hee Koo et al
Please see the question below
EARLY ACUTE REJECTION
A.FALSE Acute rejection episodes differ in their impact on graft survival depending on severity ,time of occurrence ,number of episodes and degree of recovery of function after treatment ;return to base line having no negative impact
B.TRUE TCMR without marked histological abnormalities with steroid response has good outcome
C.FALSE Functional recovery rate in that stage is high and is associated with good graft outcome
D.F.AMR is accompanied by poor graft survival due to DSA and possibility of recurrence and development of chronic allograft dysfunction associated with chronic rejection
E.FALSE Early acute rejection occurs in first 6 months.
REFERENCES
Uptodate ,kidney transplantation in adults : clinical features and diagnosis of acute renal allograft function,2021
Lammarche,C et al,cellular rejection treatment according to Bannf score in kidney transplantationrecipients ;A systematic review, Transplant Direct,2016:2:e115
Koo,HE,et al,Impact of early andlate acute rejection on graft survival in renal transplantation ,Kidney Res Clin Proced,2015,Sept;4(3):160-164
acute rejection can occur early in transplantation in patients with DR mismatches and in patients with DGF
It carries high risk of graft loss (due to recurrrent rejection and development of CAN
A. False, not always
B. True, if responded well, no further issues
C. False, the clinical significance nay not be clear
D. False , high chance of graft loss
E. False, 3 to 6 months
Early acute rejection is generally better than late rejection because in the early phase the immune system is not yet fully prime and there are few numbers of APCs, especially dendritic cells.
Advances in immunosuppressive therapy contributed to a significant reduction in T cell-mediated rejection to 10% to 20 %.
< 10% of the kidney transplants recipients developed rejection after the first year of transplantation. This is called late rejection and it is often associated with non-adherence
A single event of rejection decreases 5-year graft survival by < 10 %
Rejection appears as a sudden rise in Cr, or biopsy finding in cases of protocol biopsies, and DGF
Reference; Oxford Hand Book of Nephrology & Hypertension, second edition
The incidence of acute rejection has dramatically fallen in the previous years due to advances in immunosuppressive medication whether as induction or maintenance regimen .
Early acute rejection was found to be associated with HLA-DR mismatch and delayed graft function and lead to graft failure due to chronic allograft nephropathy and recurrent acute rejection.
Early episodes of acute rejection may also have consequences for the patients and their grafts beyond the 1st 6 months after transplantation. Greater histological severity of cellular acute rejection has been associated with inferior death-censored graft survival.
Vascular acute rejection is strongly associated with premature graft failure and the development of chronic allograft nephropathy. ABMR particularly when vascular involvement is evident, represents a high risk of graft failure in the coming 5 years.
Recipients with early acute rejection also more likely to die from cardiovascular diseases or cancer.
Reference:
Clayton Ph.A., McDonald S.P.,Russ G.R., Chadban S.J. Long-Term Outcomes after Acute Rejection in Kidney Transplant Recipients: An ANZDATA Analysis. JASN( 2019)
Acute rejection within the first six months after transplantation mostly T cell mediated a single episode of rejection reduces five years graft survival by 10% the greater the number of episodes the worse the outcome of transplantation
AR is acute worsening of allograft function manifested by tissue diagnosis.
2 forms are there
-TCMR
-Active ABMR or mixed form
CNI and antiproliferative agents significantly improved incidence of AR.
Vascular AR is associated with early graft failure and premature CAN in protocol biopsies. ABMR has the high risk of graft failure over following five years.
AR episode is high risk factor for graft loss .which is increased by severity of rejection ,late development, non recovery to baseline function .It was suggested that late AR has worse effect on long term graft survival. Increased graft loss following AR is related to extent of graft injury that leads to CAN .The associated DSA can lead to subsequent AMR.
REFERENCES
WU,K et al: The severity of acute cellular rejection defined by Banff classification is associated with kidney allograft outcomes,Transplantion97:1146-1154,2014
Acute rejection is a major risk factor for graft loss depending on
· timing of occurrence (Late acute rejection has more negative impact on graft survival).
· severity of the rejection episode (depending on banuff classification .
· Number of rejection episodes : as recurrent episode are associated with poorer out come
· triggering factor ( infection , non adherence to IS)
· response to treatment (where the graft function improved to base line or not)
So early AR is a significant risk factor for graft loss compared to no rejection
1- Jalalzadeh, M., Mousavinasab, N., Peyrovi, S., & Ghadiani, M. H. (2015). The impact of acute rejection in kidney transplantation on long-term allograft and patient outcome. Nephro-urology monthly, 7(1), e24439. https://doi.org/10.5812/numonthly.24439
2- Koo, E. H., Jang, H. R., Lee, J. E., Park, J. B., Kim, S. J., Kim, D. J., Kim, Y. G., Oh, H. Y., & Huh, W. (2015). The impact of early and late acute rejection on graft survival in renal transplantation. Kidney research and clinical practice, 34(3), 160–164. https://doi.org/10.1016/j.krcp.2015.06.003
BANFF Classification Of Rejection:
AR was defined clinically by an acute deterioration in allograft function and confirmed with tissue diagnosis. Banff borderline AR was not considered as an AR episode. Graft failure was defined as transplant nephrectomy, retransplantation, or return to long-term dialysis. Delayed graft function was defined as the need for dialysis in the 1st week.
We found that EAR was associated with male sex, HLA mismatch, and older donor. LAR was associated with young recipient age and positive PRA. HLA mismatches are well-known risk factors for AR.
We found that EAR was associated with male sex, HLA mismatch, and older donor. LAR was associated with young recipient age and positive PRA. HLA mismatches are well-known risk factors for AR.
References:
1. Joseph JT, Kingsmore DB, Junor BJ, Briggs JD, Mun Woo Y, Jaques BC, Hamilton DN, Jardine AG, Jindal RM. The impact of late acute rejection after cadaveric kidney transplantation. Clin Transplant. 2001;15:221–227.
2. Opelz G, Dohler B. Influence of time of rejection on long-term graft survival in renal transplantation. Transplantation. 2008;85:661–666.
3. Sijpkens YW, Doxiadis II, Mallat MJ, de Fijter JW, Bruijn JA, Claas FH, Paul LC. Early versus late acute rejection episodes in renal transplantation. Transplantation. 2003;75:204–208.
Early acute rejection especially acute T cell rejection if treated early and completely (steroid -responsive) could have a good prognosis.
But if there is delay in diagnosis and treatment, they will affect negatively graft survival.
It has been demonstrated that an acute rejection(AR) episode is amajor risk factor of graft loss.
However,notall rejection episodes have the same effect
factors that determine the impact are
Several studies have evaluated the difference between EARand LAR interms of impact on long-term graft survival.Somestudies have suggested that LAR has apoorer effect on long-term graft survival than EAR . It has been proposed that
differences in immunologic activity and triggering factors such as infection or nonadherence to immunosuppressive medication may be the reasons for these distinctions .
in one study both EAR and LAR . has a negative impact on graft survival . both EAR and LAR were significant risk factors for graft failure compared with the no AR group.
Recently,ElTersetal [6] showed that early acute cellular rejection was not a single acute event but triggered apersis- tent alloimmune response that might result in long-term graft
injury and graft loss years after the acute event
Many studies have been conducted to explore whether the timing of AR affects graft survival.The majority of these studies reported that LAR was correlated with poor long-
term graft survival [1–3]. However,reports about the impact of EAR are inconsistent. We thought that there as on for variable results might be that each study used different
methods and populations ,with the cut off for EAR being particularly variable.Some studies used a3-month cut off to divide EAR and LAR [1,3].
refference :
1.Eun Hee Koo, Hye Ryoun Jang,Jung Eun Lee, Jae Berm Park, Sung-Joo Kim,Dae Joong Kim, Yoon-Goo Kim,Ha Young Oh, and Wooseong Huh. The impact of early and late acute rejection on graft survival in renal transplantation. Kidney Res Clin Pract. 2015 Sep; 34(3): 160–164.
2. Joseph JT,Kingsmore DB,JunorBJ,BriggsJD,MunWooY,Jaques BC, Hamilton DN, Jardine AG,Jindal RM:The impact of late acute rejection after cadaveric kidney transplantation. Clin Transplant 15:221–227,2001
AR, regardless of its timing, significantly worsened graft survival. Treatments to reduce the incidence of AR and improve prognosis are needed.
But late acute rejection (after 1 year of transplantation)has poor prognosis than EAR .
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4608868/#
Dear All
Answer the following question with a justification of your answer (not more than 50 words): Early acute rejection
A. Always associated with reduced graft survival (False)
B. Steroid-sensitive ACR is not associated with poor graft outcome (True)
C. Mild rejection (ACR Banff 1/2A) is associated with poor graft outcome. (False)
D. Antibody-mediated rejection is not associated with poor graft outcomes if treated. (False)
E. It happened any time within the first year of transplantation (False).
JUSTIFICATION:
A- EARs are usually TCMR, low grade mild AMR, subclinical detected on protocol biopsy, usually of good outcome because of advances in IS drugs, monitoring DSA, regular follow up and protocol biopsy.
B-True.
C- mild ACR are usually steroid sensitive with good graft outcome.
D-AMR is usually complicated with recurrent, chronic ABMR, and graft loss.
E- EARs are within first 3-6 months post-transplant.
A. Wrong , it is associated reduced graft survival in 86%
B. True
C. Wrong
D. Wrong as it affect the graft survival .
E. Wrong, it is defined as rejection within the first six months after transplant
Answer the following question with a justification of your answer (not more than 50 words): Early acute rejection
A. Always associated with reduced graft survival false
B. Steroid-sensitive ACR is not associated with poor graft outcome True
C. Mild rejection (ACR Banff 1/2A) is associated with poor graft outcome False
D. Antibody-mediated rejection is not associated with poor graft outcomes if treated successfully True
E. It happened any time within the first year of transplantation True
In addition to the intensification of maintenance immunosuppression therapy, pulse glucocorticoids are usually the only additional treatment for type IA or IB, and the expected reversal rate for the first episode of acute TCMR is 60-70 %.
By 10 years after kidney transplant, up to 25% have developed de novo DSA (dnDSA). Thus, it is not surprising that AMR is the most common cause of allograft failure.
Even among patients who recover, acute rejection episodes can have a negative impact on long-term graft survival.
Acute rejection is a strong risk factor for the development of chronic allograft nephropathy. The incidence of CAN is <1 percent in patients who have had no episodes of acute rejection.
Clinical phenotypes of AMR
Early posttransplant (<30 days) active AMR
In patients with preexisting DSA, active AMR can occur within 30 days after transplantation. In general, this form of AMR is uncommon. With prompt diagnosis and treatment, patients can recover allograft function and histological features of active AMR frequently resolve completely. In other cases, the histological features of active AMR persist and chronic active AMR, allograft dysfunction, and ultimate allograft failure ensues.
Early posttransplant active ABMR presents with an abrupt allograft dysfunction in patients with DSA or immunologic amnestic response to alloantigens at the time of transplantation.
Late (>30 Days) posttransplant AMR with preexisting DSA
Many patients with preexisting DSA can develop an indolent and progressive form of AMR that is usually initially detected on a surveillance biopsy (in the setting of stable function) or on a for-cause biopsy for mild allograft dysfunction. At diagnosis, there is often minimal if any reduction in glomerular filtration rate (GFR) or proteinuria even when mild chronic features are present. Overtime, however, the GFR declines and the patient becomes proteinuric.
Late (>30 days) AMR associated with dnDSA
In the current era of sensitive DSA testing and a general avoidance of preexisting DSA, the most common form of AMR is associated with dnDSA.
dnDSA is a new DSA detected after >3 months posttransplant 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.
AMR with dnDSA is associated with inferior allograft survival when compared with AMR from preexisting DSA.
The risk of TG is higher in those with multiple episodes of acute rejection, late rejection episodes (occurring >6 months after transplantation), and increased severity of the acute rejection episodes.
Early AMR is usually C4d positive and has DSAs against either HLA class I or class II.
Fortunately, allograft function can be restored through rapid diagnosis and treatment, and the histological features of active ABMR are often completely resolved.
Immunoglobulin G (IgG) subclasses are also related to the phenotypes of ABMR. Acute ABMR is mainly accompanied by IgG3 DSA, whereas subclinical ABMR is accompanied by IgG4. Subclass IgG3 is associated with a shorter time to graft failure and C4d deposition in allograft peritubular capillaries. Subclass IgG4 is associated with a slower progression to graft failure and a lower incidence of C4d deposition. But IgG4 is associated with transplant glomerulopathy and interstitial fibrosis/tubular atrophy. T cell-mediated rejection may be more often encountered in ABMR with dnDSA than ABMR with preformed DSA.
Min Young Kim and Daniel C. Brennan. Therapies for Chronic Allograft Rejection. Frontiers in pharmacology. April 2021. Volume 12
acute graft rejection early post-transplantation could be either T cell or antibody-mediated (ABMR/TCMR) but both may coexist. acute early rejection is mostly due to preformed donor-specific antibodies and mostly aggressive entailing aggressive treatment with steroids and in case of being antibody-mediated by removal of antibodies by plasmapheresis and or addition of IVIG . mostly it leaves chronic changes. this will increase with each episode. fibrosis and tubular atrophy will lead eventually to graft failure
Long-term survival of renal allograft is significantly associated with AREs
Patients’ survival was significantly affected by the combination of DGF and rejection
AREs had no adverse effect on long-term renal graft function if they were successfully treated
The main factors for a more successful long-term allograft outcome are immunologic such as low rate of ARE and advancement of immunosuppressant agents
EARs were not as significant risk factors of chronic graft loss compared with LARs
Some previous studies argued that EARs are as much of a risk factor as LARs in chronic graft loss
However, EAR does not appear to be a risk factor of long-term successful results, it is still a major complication that increases hospital costs
Studies have shown that the number of ARE has negative impact on graft survival
Furthermore, recipients with one ARE have been found to show better survival rates than those with two or more episodes of rejection
many factors affect patient-graft survival
gender of recipients and age of donor had some influence
the timing of an acute rejection episode was associated with the success rate of patient-graft survival. Late acute rejection appears to reduce long-term allograft survival rate
Reference:
The Impact of Acute Rejection in Kidney Transplantation on Long-Term Allograft and Patient Outcome
AUTHORS
Mojgan Jalalzadeh 1 , Nouraddin Mousavinasab 2 , Said Peyrovi 3 , Mohammad Hassan Ghadiani 4 , *
Early acute rejection episodes have been reduced significantly with the introduction of CNIs in immunosuppressive protocols. In the study by OPTN, the incidence reduced from 10% in 2010 to 8% in 2017 (1)
DSA positivity, HLA mismatch, DGF, pediatric recipients, and prolonged cold ischemia time all are associated with more early acute rejection.
Acute rejection is associated with negative graft survival. However, if properly treated and graft was maintained, it has no negative outcome on prolonged graft survival (2).
References:
Hart A, Smith JM, Skeans MA, Gustafson SK, Wilk AR, Castro S, Foutz J, Wainright JL, Snyder JJ, Kasiske BL, Israni AK. OPTN/SRTR 2018 Annual Data Report: Kidney. Am J Transplant. 2020 Jan;20 Suppl s1:20-130. doi: 10.1111/ajt.15672. PMID: 31898417.
Madden RL, Mulhern JG, Benedetto BJ, O’Shea MH, Germain MJ, Braden GL, O’Shaughnessy J, Lipkowitz GS. Completely reversed acute rejection is not a significant risk factor for the development of chronic rejection in renal allograft recipients. Transpl Int. 2000;13(5):344-50. doi: 10.1007/s001470050712. PMID: 11052270.
Acute rejection impact on graft survival
Sure it will affect on it and reduce its survival specially if not treated early
But some studies show that Acute rejection in first 6 months if treated fast and cured rapidly not affect the graft survival
Acute renal allograft rejection is a major cause of allograft dysfunction. Some kidneys do not regain function even with maximal antirejection therapy.
Even among patients who recover, acute rejection episodes can have a negative impact on long-term graft survival. Acute rejection is a major predictor of interstitial fibrosis/tubular atrophy (IF/TA), formerly called chronic allograft nephropathy, which is responsible for most death-censored graft loss after the first year posttransplant
Acute rejection episodes are generally associated with a reduction in long-term allograft survival, although not all rejection episodes have the same impact on long-term graft function.
Factors such as timing of rejection, severity and number of acute rejections, and degree of recovery of function after treatment all affect the long-term outcome . If renal function returns to baseline, acute rejection does not necessarily cause irreparable damage or impact long-term graft survival
Acute graft rejection has negative impact and direct effect on graft survival and may cause prolonge renal impairment regardless the usage of medical treatment ,acute rejection is the major cause of interstitial fibrosis and tubular atrophy both lead to graft nephropathy
It’s important to evaluate pre and post transplant risk factors of acute rejection and identify it’s type and severity this happen mainly by doing graft biopsy which give idea about the proper management.
There are multiple risk factors for AR like patients with pre transplant DSA ,age ,race and subsequent transplants ,regarding post transplant risk this is related mainly to the immunosuppression regimen like using ATG in induction with TAC and MMF with or without steroid give better outcome regarding AR .
The prognosis and the effect of rejection on graft outcome depend on type and severity of the acute rejection
Reference
-Evaluation and treatment of acute rejection in kidney allograft. (2020).CJASN,15(3),430,438.
-kidney transplantation principles and practice (8ed. ).(2020).Philadilphia:STUART J.KNECHTLE ,LORNA P.MARSON,SIR PETERJ.MORRIS
Both acute rejection (AR) and allograft functions early post-transplantation correlate with long-term graft survival. A study done by Cosio FG in 1997, included 843 adult recipients of first cadaveric renal grafts, studied for a minimum of 3.5 years, found graft survival was significantly worse in patients with AR and an elevated SCr (6mo) compared with patients who had AR but low SCr(6mo) and patients without AR but with an elevated SCr(6mo) (P<0.0001), hence concluded that the SCr (10d) concentration had correlated for graft prognosis. On the other hand, several other studies have suggested that late acute rejection (LAR) has a poorer effect on long-term graft survival than EAR.
Jalalzadeh M et al, in 2015, found that late acute rejection (LAR) had a negative impact on long-term renal allograft survival (had lower 5-year graft survival rate) compared to early AR, and the risk of chronic graft dysfunction increased in patients with a history of LAR. LAR was more commonly associated with males (P = 0.001) and donors’ age (P = 0.0002). While Koo EH et al, in a study of 709 patients, 198 (30%) had biopsy-proven AR [EAR=152 patients (77%); LAR=46 patients (23%)]. The 5-year graft survival rates were 97%, 89%, and 85% for patients with no AR, EAR, and LAR, respectively. These differences were significant (P<0.001 for both). In time-dependent Cox regression analysis, EAR (hazards ratio, 3.37; 95% confidence interval, 1.90–5.99) and LAR (hazards ratio, 5.32; 95% confidence interval, 2.65–10.69) were significantly related to graft failure.
References:
1. Cosio FG, Pelletier RP, Falkenhain ME, Henry ML, Elkhammas EA, Davies EA, Bumgardner GL, Ferguson RM. Impact of acute rejection and early allograft function on renal allograft survival. Transplantation. 1997 Jun 15;63(11):1611-5.
2. Koo EH, Jang HR, Lee JE, Park JB, Kim SJ, Kim DJ, Kim YG, Oh HY, Huh W. The impact of early and late acute rejection on graft survival in renal transplantation. Kidney Res Clin Pract. 2015 Sep;34(3):160-4. doi: 10.1016/j.krcp.2015.06.003. Epub 2015 Jul 26.
3. Jalalzadeh M, Mousavinasab N, Peyrovi S, Ghadiani MH. The impact of acute rejection in kidney transplantation on long-term allograft and patient outcome. Nephrourol Mon. 2015 Jan 20;7(1):e24439. doi: 10.5812/numonthly.24439.
A. Always associated with reduced graft survival: false
the kind of rejection matters, since steroid-responsive acute T cell-mediated rejection, as well as mild cellular rejection, will have no effect on the outcome of the transplantation.
B. Steroid-sensitive ACR is not associated with poor graft outcomes. True,
C. Mild rejection (ACR Banff 1/2A) is associated with poor graft outcomes. false.
D. Antibody-mediated rejection is not associated with poor graft outcomes if treated.false
Mueller A, Schnuelle P, Waldherr R, et al. Impact of the Banff ’97 classification for histological diagnosis of rejection on clinical outcome and renal function parameters after kidney transplantation. Transplantation. 2000;69:1123–1127. 3
E. It happened any time within the first year of transplantation. false within the first 6 months, but some trials used the cutoff 1 year between early and late rejection
(The impact of early and late acute rejection on graft survival in renal transplantation Eun Hee Koo, Hye Ryoun Jang , Jung Eun Lee , Jae Berm Park , Sung-Joo Kim, Dae Joong Kim, Yoon-Goo Kim, Ha Young Oh , Wooseong Huh)
Acute rejection, irrespective of timing since transplantation, has poor rates of graft survival. Late acute rejection has a poorer effect on long term graft survival than early acute rejection.
Early acute rejection, as well as late acute rejection, have negative effects on long term graft survival. THis can be a significant factor in the development of graft failure.
According to El Ters et al, “ Early acute cellular rejection is not a single acute event, but triggers a persistent alloimmune response that might lead to long term graft injury and graft loss years after the acute event. “
MOst studies that explore whether the timing of AR affects graft survival rates have reported that LAR is more commonly seen to be related to poor long term graft survival. EAR link to graft failure does not seem to be reported in a consistent manner.
EAR incidence was found to be linked to factors such as
On the other hand, LAR was found to be linked to young recipient age, positive PRA. This could be because of non-compliance or increased immune responsiveness.
Graft biopsy, either clinical or protocol biopsy, is the gold standard to diagnose EAR, although limitations include the test being invasive, and failure in predicting AR.
Ref:
Koo EH, Jang HR, Lee JE, Park JB, Kim SJ, Kim DJ, Kim YG, Oh HY, Huh W. The impact of early and late acute rejection on graft survival in renal transplantation. Kidney Res Clin Pract. 2015 Sep;34(3):160-4. doi: 10.1016/j.krcp.2015.06.003. Epub 2015 Jul 26. PMID: 26484041; PMCID: PMC4608868.
Early acute rejection that occurs in the first 6 months post transplantation has a poor effect on graft survival either acute TCMR or acute AMR. The incidence of early acute rejection has decreased markedly due to the advances in immunosuppressive medications. The effect of late acute rejection is poorer on graft survival than early acute rejection. Early acute rejection may be associated with HLA-DR mismatches. Also inadequate immunosuppressive medications at the peak time of immune activity has a great role in early acute rejection.
Ref:
1-Early versus late acute rejection episodes in renal transplantation – PubMed (nih.gov)
2-The impact of early and late acute rejection on graft survival in renal transplantation – ScienceDirect
3-Factors Contributing to Acute Rejection in Renal Transplantation: The Role of Noncompliance – ScienceDirect
effect of early acute rejection (within the first 6 months after transplantation) on graft survival?
Early acute rejection occurs in 1st 6m post transplant. Usually mild pure TCMR or mild ABMR because
1) improvement of AB screening pre-transplant
2)recent immune suppression medications specially after the era of CNI.
3) usually detect early
4) patient usually at high side of immune suppression medications.
Some studies showed 10y graft survival in early acute rejection vs late acute rejection (84 %to40% respectively)
Reference
1.Eun Hee Koo, Hye Ryoun Jang,Jung Eun Lee, Jae Berm Park, Sung-Joo Kim,Dae Joong Kim, Yoon-Goo Kim,Ha Young Oh, and Wooseong Huh. The impact of early and late acute rejection on graft survival in renal transplantation. Kidney Res Clin Pract. 2015 Sep; 34(3): 160–164.
2. Deborah Zimmerman, Andrew A. House, S. Joseph Kim, Ronald A. Booth, Tinghua Zhang, Tim Ramsay, and Greg Knoll . The Risk of Acute Rejection Following Kidney Transplant by 25-Hydroxyvitamin D and 1,25-Dihydroxyvitamin D Status: A Prospective Cohort Study. Can J Kidney Health Dis. 2017; 4: 2054358117699822.
The risks of both death with function and death- censored graft failure is attributed to cardiovascular disease and cancer. Lower eGFR and albuminuria are recognized as independent risk factors for all-cause and cardiovascular mortality consequent to AR. The intensity of immunosuppression may affect both cardiovascular risk, through mechanisms including development of new-onset diabetes, hypertension, dyslipidemia, renal impairment and proteinuria .
Recently AR ,that occur within first 6 months after kidney transplantation is found to be associated with significant increases in risk of both death with function and graft loss due to CAN, the leading causes of transplant failure in the current era. The associations noted were strongest for those with AMR and for those where initial therapy failed to enable return to baseline serum creatinine. Despite the decline in both the incidence of AR and the incidence of early graft loss directly caused by AR, these data highlight the importance of AR as a pivotal early event after transplantation with long-lasting con- sequences.
Referance;
Organ Procurement and Transplantation Network (OPTN) and Scien-
tific Registry of Transplant Recipients: (SRTR). OPTN/SRTR 2011 Annual
Data Report, Rockville, MD, Department of Health and Human Ser-
vices, Health Resources and Services Administration, Healthcare Sys-
tems Bureau, Division of Transplantation, 2012
Australia and New Zealand Dialysis and Transplant Registry: 39th An-
nual Report, Chapter 8, Transplantation. Australia and New Zealand
Dialysis and Transplant Registry, Adelaide, Australia, 2016
McDonald S, Russ G, Campbell S, Chadban S: Kidney transplant re-
jection in Australia and New Zealand: Relationships between rejection
and graft outcome. Am J Transplant 7: 1201–1208, 2007
Meier-Kriesche HU, Schold JD, Srinivas TR, Kaplan B: Lack of improve-
ment in renal allograft survival despite a marked decrease in acute re-
jection rates over the most recent era. Am J Transplant 4: 378–383, 2004
OʼConnell PJ, Kuypers DR, Mannon RB, Abecassis M, Chadban SJ, Gill
JS, et al.: Clinical trials for immunosuppression in transplantation:
case for reform and change in direction. Transplantation 101: 1527–
1534, 201
Acute rejection episode associated with increased risks of longer-term graft failure
and death, particularly death from cardiovascular disease and cancer.
Factors affect survival:
Timing (EAR VERSUS LAR), severity and return of graft to function affect long-term graft
outcome. Immunologic activity and triggering factors such as infection or nonadherence
to immunosuppressive may also add effect.
Some studies have suggested that LAR and EAR has SIMILAR effect on long-term graft
survival.
Hi Mohammed, please supplement your answer with literature evidence. I want to know the effect of acute rejection on graft survival
The complication associated with acute rejection is graft failure if not treated
appropriately and timely fashion. Even after the treatment, there is an
association of poor graft survival after each episode of rejection.
Reference:
Ruchi H. Naik; Saed H. Shawar. renal Transplantation Rejection. StatPearls
,July 25, 2021.
Early acute rejection
A. Always associated with reduced graft survival —-False
B. Steroid-sensitive ACR is not associated with poor graft outcome—True
C. Mild rejection (ACR Banff 1/2A) is associated with poor graft outcome—–False
D. Antibody-mediated rejection is not associated with poor graft outcomes if treated—True
E. It happened any time within the first year of transplantation—Fasle
Development of immunosuppressive protocols decreased the rate of acute rejection and lowered the rate of chronic rejection and improve long-term graft survival.
The Banff classification for AMR identifing and demonstrating pathologic features and diagnostic criteria to better understand
Treatment of AMR has produced a variety of results, some of them suboptimal, affecting the development of standardized protocols
Newer therapies are promising,
Hi Dr Doaa, please out forward published evidence to support your true and false statements
Thanks, Doaa
AMR is always associated with poor graft outcomes even with effective treatment. It represents a severe rejection
The decrease in acute rejection incidence is rendered to marked improvements in 1-year graft survival, after the introduction of cyclosporine and T cell–depleting induction .
It was categorised as steroid responsive and steroid non responsive ,
It is classified as T cell mediated or antibody mediated.
Acute rejection risk depends on immunologic risk at the pretransplantion period depending on pretransplant DSA and HLA A/B/DR mismatch being the main factor as well as number of transplants, recipient’s age and race.
In post transplantation period acute rejection risk is dependent upon immunosuppression regimen and exposure.
The gold standard for diagnosing acute rejection in kidney transplant recipients is tissue biopsy. Allograft histology is interpreted using the Banff classification of kidney allograft pathology
· Banff grade 1a with moderate lymphocytic infiltration of the tubules
· Banff grade 1b with severe lymphocytic interstitial infiltration and tubulitis .
· Banff grade 2a with arterial intimal lymphocytic infiltration .
· Peritubular lymphocytic infiltration characteristic of antibody-mediated rejection.
· Positive C4d staining of the peritubular capillaries by immunohistochemistry.
the Banff classification required three features for diagnosis:
(1) active tissue injury,
(2) immunohistologic evidence of peritubular capillary complement split-product C4d deposition,
(3) circulating DSA.
The revised 2013 Banff criteria for antibody-mediated rejection diagnosis removed the requirement for C4d detection and included the evidence of current/recent antibody interaction with vascular endothelium,” which may include either
(1) positive C4d staining,
(2) at least moderate microvascular inflammation, or
(3) increased expression of endothelial gene transcripts .
The most recent Banff studies showed a lack of DSA with significant microvascular inflammation and low false positive rate of C4d staining, and removed the need of documented circulating DSA with positive C4d staining and microvascular inflammation
Studies of urine and blood biomarkers, such as CXCL9, CXCL10, granzyme B, perforin, and Fas ligand, have shown variable efficacy for identifying acute rejection, differentiating T cell–mediated rejection from antibody-mediated rejection
Decreased urinary miR-210 levels have been associated with T cell–mediated rejection and subsequent 1-year GFR decline
donor-derived cellfree DNA (cf-DNA) profiling has been used in the noninvasive diagnosis of antibody-mediated rejection,
noninvasive biomarkers have failed to completely replace tissue diagnosis
Reference
Cooper JM. Evaluation and Treatment of Acute Rejection in Kidney Allografts .CJASN March 2020, 15 (3) 430-438
Early acute rejection:
A- Always associated with reduced graft survival. (F)
B- Steroid-sensitive ACR is not associated with poor graft outcome. (T)
C- Mild rejection (ACR Baff 1/2A) is associated with poor graft outcome. (F)
D- Antibody-mediated rejection is not associated with poor graft outcomes if treated. (F)
E- It happened any time within the first year of transplantation. (F)
Not all rejection attacks should be assumed equal, and the pathologic processes of the rejection episode, the severity, and the response to therapy (recovery of the graft function to baseline) expect the long-term outcome. T-cell–mediated rejection is an important cause of early allograft failure, but is a less common cause of late allograft failure except in cases of drug non-adherence. Acute rejections that occur late (after the first 3 months) is more predictive of chronic allograft failure than those that occur during the first 3 months; rejections that occur very early and are reversed may have little or no effect on the outcome. More severe rejection and multiple rejection episodes are more likely to predict late allograft failure.
Hi Dr Jamila, I want to know the effect of early acute rejection (within the first 6 months after transplantation) on graft survival. Please provide literature evidence that supports your answer
EAR is a major barrier to improving long-term graft survival. Graft biopsy, either clinical biopsy or protocol biopsy, consedered the gold standard for diagnosing EAR. For the prevention and early detection of EAR, an immunologic monitoring method developed that can stratify risky patient to predict AR and choose immunosuppressive protocol.
Refere
Eun Hee Koo et AL, The impact of early and late acute rejection on graft survival in renal transplantation,
Kidney Research and Clinical Practice,
Volume 34, Issue 3,
2015,
Pages 160-164,
ISSN 2211-9132,
https://doi.org/10.1016/j.krcp.2015.06.003.
(https://www.sciencedirect.com/science/article/pii/S2211913215300036)
-Rate of acute rejection (AR) and graft survival have steadily improved over time but still acute rejection is a major risk factor of graft loss and not all rejection episodes have the same effect.
Long-term graft outcome affect by:
1. severity of rejection.
2. Timing of rejection as early or late acute rejection.
3. Recovery of allograft to the baseline function after rejection.1
-AR is a risk factor for chronic rejection.
–AR classifies into the following :
1. Antibody-mediated rejection: It is usually demonstrated evidence of circulating DSA and immunological evidence of antibody-mediated injuries to the kidney(glomerulitis, peritubular capillaritis)
2. Acute T-cell mediated rejection: it is characterized by lymphocytic infiltration of tubules, interstitium, and sometimes the arterial intima.
–Predisposing factors for acute rejection include the number of HLA mismatches, delayed graft function, deceased donor, repeat transplant, PRA level, race, female gender.2
-Some studies have suggested that late acute rejection has a poorer effect on long-term graft survival than early rejection, and recent studies showed that early rejection was not the cause of graft failure.
-A cohort of 654 patients who underwent cadaveric renal transplants (1983-1997) that functioned for more than 6 months was studied. In 384 0f 654 transplant recipients, one or more treated ARs were documented, the last AR occurred in 297 within 3 months and 87 after 3months. Ten-year graft survival rates censored for causes of graft loss other than chronic rejection were 94%( patient without AR),86 % (patients with early AR), and 45% (patient with late AR).3
-Late AR has a serious impact on long-term graft survival and is associated with MHC class I incompatibility while early AR is correlated with HLA-DR mismatches and has a better prognosis.3
References:
1.Eun Hee Koo, Hye Ryoun Jang,Jung Eun Lee, Jae Berm Park, Sung-Joo Kim,Dae Joong Kim, Yoon-Goo Kim,Ha Young Oh, and Wooseong Huh. The impact of early and late acute rejection on graft survival in renal transplantation. Kidney Res Clin Pract. 2015 Sep; 34(3): 160–164.
2. Deborah Zimmerman, Andrew A. House, S. Joseph Kim, Ronald A. Booth, Tinghua Zhang, Tim Ramsay, and Greg Knoll . The Risk of Acute Rejection Following Kidney Transplant by 25-Hydroxyvitamin D and 1,25-Dihydroxyvitamin D Status: A Prospective Cohort Study. Can J Kidney Health Dis. 2017; 4: 2054358117699822.
3. Yvo W J Sijpkens , I.I Doxiadis,Kamel Mallat ,Johan W de Fijter. Early versus late acute rejection episodes in renal transplantation .Reseach gate.February 2003Transplantation 75(2):204-8
Late ARE has a detrimental impact on long-term graft survival and is associated with MHC class I incompatibility, whereas early ARE is correlated with HLA-DR mismatches and has a better prognosis. These data are consistent with the role of direct and indirect allorecognition in the pathophysiology of early and late ARE, respectively.
early TCMR (even borderline or subclinical) is linked to ongoing inflammation (i), the subsequent development of moderate/severe graft interstitial fibrosis (GIF), transplant glomerulopathy (TG) and a higher rate of de novo Class II DSA. Indeed, those patients with early TCMR whose pathology evolves on the follow-up biopsy have an increased incidence of alloimmune mediated graft loss associated with TG and GIF.
early TCMR leads to the development of de novo DSA, which in turn could result in AMR and the evolution of TG.
acute and chronic; early and late; clinical and subclinical; and classify rejection as TCMR and AMR, its role is to protect the host at all costs and by whatever mechanisms are available.
We suggest that the immune system provides an integrated response to achieve allograft rejection with TCMR and AMR being either linked through time or coexisting. If such is the case, then it behoves us to keep T cells in the forefront, alongside B cells/plasma cells and DSA, in order to improve long-term outcomes.
Dear All
Answer the following question with a justification of your answer (not more than 50 words): Early acute rejection
A. Always associated with reduced graft survival
B. Steroid-sensitive ACR is not associated with poor graft outcome
C. Mild rejection (ACR Banff 1/2A) is associated with poor graft outcome
D. Antibody-mediated rejection is not associated with poor graft outcomes if treated
E. It happened any time within the first year of transplantation
There is a reward for the correct answer.
EAR occur in first 6 months post transplantation, not all rejection episodes had same effect on graft outcome, the outcome determined by severity of rejection episode& response to treatment & if full recovery accomplished. So if the episode was mild & full recovery accomplished after treatment the outcome will be good. Mild acute cellular rejection constitute about half of all ACR, & it respond to pulse steroids ( 70% of it is steroid responder) with good graft outcome.
A. Always associated with reduced graft survival- F
Episodes of EAR was reported by several studies to be more benign than episodes of LAR this may be explained by the lower incidence and severity of ABMR which is associated with lower graft survival, Moreover attacks of TCMR are usually mild responding well to corticosteroids
This may be explained by the following :
So … early AR episodes are usually mild ABMR, TCMR or subclinical rejection
B. Steroid-sensitive ACR is not associated with poor graft outcome T
C. Mild rejection (ACR Banff 1/2A) is associated with poor graft outcome F
D. Antibody-mediated rejection is not associated with poor graft outcomes if treated F
E. It happened any time within the first year of transplantation F
REFERANCES
1. Wu K, Budde K, Schmidt D, et al. The Relationship of the Severity and Category of Acute Rejection With Intimal Arteritis Defined in Banff Classification to Clinical Outcomes. Transplantation 2015; 99:e105.
2. Wiebe C, Gibson IW, Blydt-Hansen TD, et al. Evolution and clinical pathologic correlations of de novo donor-specific HLA antibody post kidney transplant. Am J Transplant 2012; 12:1157.
Early acute rejection:
A. False: Not all rejection episodes have the same impact on long-term graft function. Factors such as timing of rejection, severity and number of acute rejections, and degree of recovery of function after treatment all affect the long-term outcome (Opelz G, Döhler B, Collaborative Transplant Study Report. Influence of time of rejection on long-term graft survival in renal transplantation. Transplantation 2008; 85:661
B. True: If kidney function returns to baseline, Steroid-sensitive ACR is not necessarily associated with poor graft outcome (Madden RL, Mulhern JG, Benedetto BJ, et al. Completely reversed acute rejection is not a significant risk factor for the development of chronic rejection in renal allograft recipients. Transpl Int 2000; 13:344)
C.True:(ACR Banff 1/2A) predispose to generation of DSA and ABMR with negative impact on long term graft survival.
D.False: Usually ABMR associated with poor graft outcome due to persistent of memory plasma cells producing DSAs.
E. False: Occurs within the first 6 months post transplant.
Dear Dr Ahmed,
I think choice B is the right answer.
Acute rejection may cause a negative impact on allograft survival except in conditions when it is of a mild degree and there is full recovery of kidney functions (1).
The development of subclinical and clinical DSA is associated with decreased long term allograft survival as illustrated in the attached graph (2).
References:
1) Daniel C Brennan, Tarek Alhamad, and Andrew Malone. Kidney transplantation in adults: Clinical features and diagnosis of acute renal allograft rejection. © 2021 UpToDate. (Accessed on 14 December 2021).
2) Danovitch GM. Handbook of Kidney Transplantation. Sixth Edition, Wolters Kluwer, eISBN 9781496388841, 2017.
Acute rejection (AR) episode associated with increased risks of longer-term graft failure
and death, particularly death from cardiovascular disease and cancer.
Factors affect survival:
Timing (EAR VERSUS LAR), severity and return of graft to function affect long-term graft
outcome. Immunologic activity and triggering factors such as infection or nonadherence
to immunosuppressive may also add effect.
Some studies have suggested that LAR and EAR has SIMILAR effect on long-term graft
survival.
Answer to question:
A- False. EAR depend on time, severity degree of return to normal.
B-False T, here was no significant difference in the incidence of chronic rejection based
on whether the first acute rejection episode was steroid resistant or steroid responsive.
C-False, Pulse steroid therapy for grade I acute T cell mediated rejection.
Anti-T cell agents for grade II acute TCM
D-False Even after the treatment, there is an association of poor graft
survival after each
Episode of rejection.
E. False. The timing of acute rejection onset (early, < or= 60 days vs. late,> 60 days post-
transplant.
Early Acute Rejection
A is false ; For kidney and liver grafts, steroid-sensitive ACR has little impact on ultimate outcome.
B is true ; lack of effect of T cell–mediated rejection on long-term outcome has been well documented
( Halloran PReeve JP, Pereira AB, et al. Antibody-mediated rejection, T cell-mediated rejection, and the injury-repair response: New insights from the Genome Canada studies of kidney transplant biopsies. Kidney Int 2014; 85: 258–264.)
C is false. Banff group 1A,1B &2A are responding to therapy,so when treated properly in time will not affect the graft outcome.
{ However, the complete functional response rates of Banff grade 1 pooled and grade 1B separately (44-73%) overlapped with those of Banff grade 2A (52-80%), whereas lower figures were reported for Banff grade 2B rejections (10%)}
((Transplant Direct. 2016 Dec; 2(12): e115.
Published online 2016 Nov 15. doi: 10.1097/TXD.0000000000000626
PMCID: PMC5142362
PMID: 27990480))
D is True. treated AMR with good response rate is associated with high survival rate of the graft.
In a pilot study of 7 AMR patients treated using PLEX and IVIG at 100 mg/kg/d for 3 days, then 3 times per week for 2-4 weeks, then rituximab 500 mg/m2 for 1 dose if AMR was ongoing at week 4, Mulley et al found 100% graft survival at 21-month follow-up.60 As mentioned earlier, Lefaucheur et al conducted a retrospective study of 12 AMR patients compared with historic control (IVIG). The treatment group received PLEX and IVIG 100 mg/kg × 4 doses, then IVIG 2 g/kg every 3 weeks × 4 doses, and rituximab 375 mg/m2/week × 2 doses. Graft survival was 91.7% in the treatment group vs 50% in the control group. Kaposztas et al performed a retrospective study of 54 AMR patients compared with historic control (PLEX and IVIG).61 The treatment group received rituximab 500 mg/m2, PLEX, and IVIG 500 mg/kg if an immunoglobulin G deficiency was noticed. Graft survival was 90% in the treatment group vs 60% in the control group.
{Antibody-Mediated Rejection: A Review
Jorge Carlos Garces, Sixto Giusti, Catherine Staffeld-Coit, Humberto Bohorquez, Ari J. Cohen, George E. Loss
Ochsner J. 2017 Spring; 17(1): 46–55. PMCID: PMC5349636}
E is false.
early acute rejection is referred to time period of the first 3 to 6 months post-transplantation.
true answers B and D
Early acute rejection
A. Always associated with reduced graft survival…F usually respond to treatment with full recovery if treated early
B. Steroid-sensitive ACR is not associated with poor graft outcome…F
Associated with good graft outcomes
C. Mild rejection (ACR Banff 1/2A) is associated with poor graft outcome..F
Usually respond to steroids with good graft survival
D. Antibody-mediated rejection is not associated with poor graft outcomes if treated…F
acute ABMR associated with poor graft survival with risk of recurrence, chronic ABMR and TG
E. It happened any time within the first year of transplantation..F
Early mean T 1st 6m post transplant
A- False, EAR not always associated with poor graft outcome it depends on the type and the severity of AR plus the response to the therapy if mild form of AR with complete response usually has favorable graft outcome (1)
B-True, mild TCMR with no significant histological changes and steroid responsive has favor outcome(3).
C-True, early TCMR may trigger persistent alloimmune response with denovo DSA expression and increase the risk of AMR (2).
D- FLASE AMR associated with poor graft survival as its associated with DSAs, Denovo DSA and risk of recurrence and progress to chronic allograft dysfunction with Chronic rejection.
E-False, early acute rejection limited to the first 6 months (3).
References:
1-The impact of early and late acute rejection on graft survival in renal transplantation
Eun Hee Koo,1 Hye Ryoun Jang,1 Jung Eun Lee,1 Jae Berm Park,2 Sung-Joo Kim,2 Dae Joong Kim,1 Yoon-Goo Kim,1 Ha Young Oh,1 and Wooseong Huh1, Kidney Res Clin Pract. 2015 Sep; 34(3): 160–164.
2-Impact of acute rejection episodes on long-term renal allograft survival:
Jianyong Wu 1, Jianghua Chen, Yimin Wang, Jianguo Zhang, Zong Zhu, Zhangfei Shou, Suya Wang, Ping Zhang, Hongfeng Huang, Qiang HeChin Med J (Engl). 2003 Nov;116(11):1741-5.
3-up to date ,medicine ,kidney transplantation in adult: clinical features and diagnosis of acute renal allograft rejection , 2021.
Answer the following question with a justification of your answer (not more than 50 words): Early acute rejection
A. Always associated with reduced graft survival
B. Steroid-sensitive ACR is not associated with poor graft outcome
C. Mild rejection (ACR Banff 1/2A) is associated with poor graft outcome
D. Antibody-mediated rejection is not associated with poor graft outcomes if treated
E. It happened any time within the first year of transplantation
Answer:
A. False- early acute rejection is not always associated with reduced graft function.
a. Cellular rejection banff 1A, 1B and borderline without involving vascular has good prognosis
b. One episode of acute rejection which resolves with treatment to pre-rejection creatinine has good graft survival compared with no AR
B. True- steroid sensitive ACR is usually did not differ in term of graft survival compared with whom did not had AR
C. False -Mild rejection (ACR Banff 1/2A) usually respond well to treatment and did not associated with poor graft function
D. False-Antibody mediated rejection has been associated with increased risk of graft loss and effective therapy has been lacking
E. False -early acute rejection has been classified according 3-6months or usually within 6 months
References
1. Clayton, P., McDonald, S., Russ, G. and Chadban, S., 2019. Long-Term Outcomes after Acute Rejection in Kidney Transplant Recipients: An ANZDATA Analysis. Journal of the American Society of Nephrology, 30(9), pp.1697-1707.
2. El Ters, M., Grande, J., Keddis, M., Rodrigo, E., Chopra, B., Dean, P., Stegall, M. and Cosio, F., 2013. Kidney Allograft Survival After Acute Rejection, the Value of Follow-Up Biopsies. American Journal of Transplantation, 13(9), pp.2334-2341.
3. Sellarés, J., de Freitas, D., Mengel, M., Reeve, J., Einecke, G., Sis, B., Hidalgo, L., Famulski, K., Matas, A. and Halloran, P., 2011. Understanding the Causes of Kidney Transplant Failure: The Dominant Role of Antibody-Mediated Rejection and Nonadherence. American Journal of Transplantation, 12(2), pp.388-399.
4. Cooper, J., 2020. Evaluation and Treatment of Acute Rejection in Kidney Allografts. Clinical Journal of the American Society of Nephrology, 15(3), pp.430-438.
A : FALSE
B : TRUE
C : FALSE
D : FALSE
E : FALSE
Early detection and identifying the type of rejection with proper management give good result regarding graft function and survival ,graft rejection is divided into hyperacute,acute and chronic rejection.
Acute rejection occurs within first 6 months post transplant with multiple causes like cellular, numeral and CNI toxicity and ATN ,AMR has poor prognosis even with proper treatment.
Early acute rejection
A. Always associated with reduced graft survival
False
As single episode of cellular rejection with no vascular component which respond well to treatment have graft survival rate to 5 years as those without rejection
B. Steroid-sensitive ACR is not associated with poor graft outcome
True
As cellular rejection that respond well to treatment is not associated with worse graft outcome
C. Mild rejection (ACR Banff 1/2A) is associated with poor graft outcome
False
As severe grade of rejection is associated with more severe graft loss
D. Antibody-mediated rejection is not associated with poor graft outcomes if treated
False
As AMR significantly impact the graft survival even if treated
E. It happened any time within the first year of transplantation
False
early acute rejection is rejection within 3-6 months post transplant
McDonald, S., Russ, G., Campbell, S. and Chadban, S., 2007. Kidney transplant rejection in Australia and New Zealand: relationships between rejection and graft outcome. American journal of transplantation, 7(5), pp.1201-1208.
Clayton, P.A., McDonald, S.P., Russ, G.R. and Chadban, S.J., 2019. Long-term outcomes after acute rejection in kidney transplant recipients: an ANZDATA analysis. Journal of the American Society of Nephrology, 30(9), pp.1697-1707.
Loheac C, Aubert O, Assayag M, et al. Thymoglobulin induction decreases risk of ABMR and death in kidney recipients. Transplantation. 2018;102:S401.
A. Always associated with reduced graft survival False
Not always , according to the type and severity and if diagnosed early and treated promptly associated with good outcome
B. Steroid-sensitive ACR is not associated with poor graft outcome True
C. Mild rejection (ACR Banff 1/2A) is associated with poor graft outcome False
It’s associated with good graft survival
D. Antibody-mediated rejection is not associated with poor graft outcomes if treated True
E. It happened any time within the first year of transplantation False
It occurs during the first 3-6 months posttransplantation
Early acute rejection
A-always associated with reduced graft survival ? TRUE
Recently AR ,that occur within first 6 months after kidney transplantation is found to be associated with significant increases in risk of both death with function and graft loss due to CAN, the leading causes of transplant failure in the current era. The associations noted were strongest for those with AMR and for those where initial therapy failed to enable return to baseline serum creatinine. Despite the decline in both the incidence of AR and the incidence of early graft loss directly caused by AR, these data highlight the importance of AR as a pivotal early event after transplantation with long-lasting con- sequences.
Australia and New Zealand Dialysis and Transplant Registry: 39th An- nual Report, Chapter 8, Transplantation. Australia and New Zealand Dialysis and Transplant Registry, Adelaide, Australia, 2016
B- steroid sensitive ACR is not associated with poor graft out come ? TRUE
Steroid sensitive ACR found to be associated with better graft outcome . The response to high-dose corticosteroid therapy for the treatment of acute renal allograft rejection correlates with the expression level and characteristics of T cells and macrophages infiltrating into the renal allograft. These findings indicate that steroid resistance resides in specific cell populations and is not a feature of all lymphocytes.
J. Galon, D. Franchimont, N. Hiroi, G. Frey, A. Boettner, M. Ehrhart-Bornstein, et al. Gene profiling reveals unknown enhancing and suppressive actions of glucocorticoids on immune cells
FASEB J., 16 (1) (2002 Jan), pp. 61-71
C-mild rejection is associated with poor graft outcome ? TRUE
All types of ACR affect long-term graft survival. Vascular or late ACR predict poorer graft survival; the extent of tubulointerstitial inflammation (TI) is of no prognostic significance for vascular rejection.
The severity of acute cellular rejection defined by Banff classification is associated with kidney allograft outcomes2014 Jun 15;97(11):1146-54. doi: 10.1097/01.TP.0000441094.32217.052014 Jun 15;97(11):1146-54. doi: 10.1097/01.TP.0000441094.32217.05.
D- antibody-mediated rejection is not associated with poor graft outcome ,if treated? False
AMR treatment reduced biopsy-associated and serological markers of AMR, but did not affect DSA-DQ.
de Sousa MV, Gonçalez AC, de Lima Zollner R, Mazzali M. Ann Transplant. 2020 Nov 17;25:e925488. doi: 10.12659/AOT.925488.
E- it happened any time within the first year of transplantation ? FALSE
ACR , is defined as rejection ,that occur within first 6 months after kidney transplantation .
Organ Procurement and Transplantation Network (OPTN) and Scien- tific Registry of Transplant Recipients: (SRTR). OPTN/SRTR 2011 Annual Data Report, Rockville, MD, Department of Health and Human Ser-
vices, Health Resources and Services Administration, Healthcare Sys- tems Bureau, Division of Transplantation, 2012
Early acute rejection
A. Always associated with reduced graft survival
B. Steroid-sensitive ACR is not associated with poor graft outcome
C. Mild rejection (ACR Banff 1/2A) is associated with poor graft outcome
D. Antibody-mediated rejection is not associated with poor graft outcomes if treated
E. It happened any time within the first year of transplantation
True: B,D
False: A, C, E
A. Always associated with reduced graft survival
False: If early acute rejection is mild ACR Banff I/IIa, it has excellent response to treatment with no significant adverse effect on graft survival. (1)
B. Steroid-sensitive ACR is not associated with poor graft outcome
True: Mild rejection, Banff I/IIa are usually steroid sensitive, and have excellent graft prognosis. (1)
C. Mild rejection (ACR Banff 1/2A) is associated with poor graft outcome
False: The functional reversibility rates of Banff I/IIa are high and those of higher stages are low. Hence Banff I/IIa are associated with good graft outcome. (1)
D. Antibody-mediated rejection is not associated with poor graft outcomes if treated
True: Early AMR, if diagnosed and treated timely, may lead to complete reversal of clinical and histological dysfunction. But if not treated, would lead to chronic ABMR and graft loss. In contrast, late AMR is associated with poor graft outcomes, even if treated timely. (2)
E. It happened any time within the first year of transplantation
False: Early acute rejection is defined differently by different authors, but mostly as the rejection taking place in first 3 to 6 months post transplant
References:
1) Lamarche C, Cote JM, Senecal L, et al. Efficacy of Acute Cellular Rejection Treatment According to Banff Score in Kidney Transplant Recipients: A Systematic Review. Transplant Direct 2016;2:e115.
2) Schinstock CA, Manno RB, Budde K, et al. Recommended Treatment for Antibody-mediated Rejection After Kidney Transplantation: The 2019 Expert Consensus From the Transplantation Society Working Group. Transplantation 2020;104:911-922.
Acute rejection is classified into humoral and cellular although both T and B cells are involved in both types of rejections.
Acute rejection happens any time within the first year of transplantation, but more frequently in the first few months. Acute antibody mediated rejection is always associated with reduced graft survival as the presence of DSA alone even without histologic confirmation of acute rejection is associated with adverse renal outcomes. However mild cellular rejection (ACR Banff 1/2A) due to under-immunosuppression, if managed appropriately, carries no poor prognosis. Steroid-sensitive ACR is not associated with poor graft outcome
A. Always associated with reduced graft
survival. False
early ARE has a better prognosis. The graft survival after early ARE is not severely compromised
B. Steroid-sensitive ACR is not associated with poor graft outcome. true
C. Mild rejection (ACR Banff 1/2A) is associated with poor graft outcome. false
Acute vascular rejection is an adverse prognostic feature compared with tubulointerstitial rejection
D. Antibody-mediated rejection is not associated with poor graft outcomes if treated..false
Antibody-mediated rejection (AMR), particularly when vascular involvement is evident, have a high risk of graft failure over the ensuing 5 years.
E. It happened any time within the first year of transplantation. false
An early ARE was defined as an ARE occurring within 3 to 6 months post transplantation
Reference
1-YVO W. J. SIJPKENS. EARLY VERSUS LATE ACUTE REJECTION EPISODES IN RENAL TRANSPLANTATION. Vol. 75, 204–208, No. 2, January 27, 2003
Printed in U.S.A.
2-Philip A. Clayton,1,2,3 Stephen P. McDonald,1,2,3 Graeme R. Russ,1,2,3 and Steven J. Chadban1,4,5. Long-Term Outcomes after Acute Rejection in Kidney Transplant Recipients: An ANZDATA Analysis. JASN 30: 1697–1707, 2019
3-Eun Hee Koo 1, Hye Ryoun Jang 1, The impact of early and late acute rejection on graft survival in renal transplantation. 2015. The Korean Society of Nephrology. Published by Elsevier.
Dear All
Answer the following question with a justification of your answer (not more than 50 words): Early acute rejection
A. Always associated with reduced graft survival
graft outcome is better in non rejection state than in the presence of any rejection
and it is better in EAR than LAR .
THE PROGNOSIS depend on
B. Steroid-sensitive ACR is not associated with poor graft outcome — true
T cell-mediated rejection (TCMR) which respond to is , has little effect on outcomes
C. Mild rejection (ACR Banff 1/2A) is associated with poor graft outcome —- false
mild ACR ( not involving vessels ) has good prognosis , but prognosis is worsen as the sevesrity of vascular injury is increased
D. Antibody-mediated rejection is not associated with poor graft outcomes if treated
false
AMR usually associated with bad outcome and usually end by graft failure because on chronic allograft rejection .
Up to 8-year posttransplantation, death-censored graft survival (DCGS) rates of control, borderline, TCMR I, and TCMR II/III groups were 97.6%, 93.3%, 79.6%, and 73.6% (log rank test, P<0.001); the control group had significantly higher DCGS rate than the three ACR groups (each pairwise comparison yields P<0.05). The DCGS rate of late ACR was significantly lower compared with early ACR (63.6% vs. 87.4%, P<0.001). Intimal arteritis (Banff v-lesion) was an independent histologic risk factor correlated with long-term graft loss regardless of the timing of ACR. The v-lesions with minimal or high-grade tubulitis displayed similar graft survival (72.7% vs. 72.9%, P=0.96).
E. It happened any time within the first year of transplantation
true
reffrences
A- False.
According to BANFF classification if mild it will respond to treatment.
B-True.
It associated with good graft outcomes.
C-False.
Respond to treatment and associated with good graft outcomes.
D-False.
It associated with recurrence or chronic rejection.
5-False.
Early means first 6 month post- transplantation.
. An acute rejection (AR) episode is a major risk factor of graft loss. However, not all rejection episodes have the same effect. Severity of rejection histologic severity of cellular AR has been associated with inferior death-censored graft survival. Vascular AR in particular has been strongly associated with premature graft failure and histologically with premature development of chronic allograft nephropathy (CAN) . Antibody-mediated rejection (AMR), particularly when there is vascular involvement carry a high risk of graft failure over the 5 years. Timing of rejection as early (EAR) or late acute rejection (LAR), late acute rejections are associated with worse prognosis and inferior graft survival. Development of de novo DSA, non adherence or suboptimal immunosuppression and recurrent acute rejection episodes are important risk factors for LAR. Close monitoring of these patiens, making an early diagnosis and intensive treatment of LAR may help improve graft survival and long term outcome .
Allograft recovers to the baseline function after rejection are known to affect the long-term graft outcome .
Treatment for AR with high-dose steroids and/or lymphocyte-depleting antibodies lead to increased risk of sepsis and cancer, potentially leading to death with a functioning graft. Inferior graft function, proteinuria, and increased immunosuppression may also heighten cardiovascular risk, thereby predisposing affected recipients to cardiovascular morbidity and mortality.
1- Philip A. Clayton, Stephen P. McDonald, Graeme R. Russ and Steven J. Chadban
JASN September 2019, 30 (9) 1697-1707; DOI: https://doi.org/10.1681/ASN.2018111101 2 –Nephrology Dialysis Transplantation, Volume 30, Issue suppl_3, May 2015, Page iii665, https://doi.org/10.1093/ndt/gfv203.11
Acute rejection is still a major complication after renal transplantation. The overall incidence of acute rejection varies between 10% and 50% within the first 6 months
depending on the degree of human leukocyte antigen (HLA) matching and treatment used for immunosuppression .
Not all acute rejection episodes (AREs) result in an adverse outcome.
Therefore, it is important to define what kind of ARE is associated with late graft loss
. Acute vascular rejection is an adverse prognostic feature compared with
tubulointerstitial rejection
The occurrence of both interstitial and vascular rejection is associated with HLA-DR mismatches and delayed graft function, but the risk of developing vascular rejection is decreased in patients receiving cyclosporine compared with those receiving azathioprine
A severe ARE exerts a more detrimental effect on long-term outcome than an ARE with complete functional recovery
. No single factor could differentiate between the two entities, but
Recipients with repeated AREs have lower graft survival rates than those with no or only one episode
Timing of the ARE has an impact on long-term outcome. An ARE within the first 3 months may have no effect on chronic rejection ,whereas an ARE occurring after 3 or 6 months confers the greatest risk
Reference
YVO W. J. SIJPKENS. EARLY VERSUS LATE ACUTE REJECTION EPISODES IN RENAL TRANSPLANTATION. Vol. 75, 204–208, No. 2, January 27, 2003
Printed in U.S.A.
early acute rejection decrese graft survival and more graft loss.
In a cohort of cadaveric renal transplants patients ,Ten-year graft survival rates censored for causes of graft loss other than chronic rejection were 94%, 86%, and 45% for patients without acute rejection, with early acute rejection, and with late acute rejection, respectively. 1
In a 6 year study acute rejection occurred in 34 cases . 12 out of 34 had early acute rejection. The graft survival is shorter in the fourth year 87% compared to those without rejection 94%. Graft loss is more 1/12 compared with those without rejection6/114 but less than late 2
In a small study comparing between re-transplant and first transplant, the rate of acute AMR was similar between both groups but the acute TCMR was more in re-transplant group. Interestingly, the one year survival and graft survival were comparable3
A large study of 13614 recipients confirmed the association between acute rejection within 6 months post transplant and
graft loss attributed to chronic allograft , death with a functioning graft and with death due to cardiovascular disease and cancer , even after subtyping according to biopsy-proven, antibody-mediated, or vascular rejection, or response to treatment , same results were obtained4
1-Sijpkens YW, Doxiadis II, Mallat MJ, de Fijter JW, Bruijn JA, Claas FH, Paul LC. Early versus late acute rejection episodes in renal transplantation. Transplantation. 2003 Jan 27;75(2):204-8. doi: 10.1097/01.TP.0000041722.34000.21. PMID: 12548124.
2-Esra Baskin, Asli Kantar, Kaan Gulleroglu, Esra Ozmen, Handan Ozdemir, Mahir Kirnap, Gokhan Moray, Mehmet Haberal, SP873
EFFECTS OF LATE ACUTE REJECTION ON GRAFT SURVIVAL AND OUTCOME IN PEDIATRIC RENAL TRANSPLANT RECIPIENTS, Nephrology Dialysis Transplantation, Volume 30, Issue suppl_3, May 2015, Page iii665, https://doi.org/10.1093/ndt/gfv203.11
3- Lan Zhu et al ,Patterns of Early Rejection in Renal Retransplantation: A Single-Center Experience Journal of Immunology Research, 2016, 2697860 – December 2016 ,https://doi.org/10.1155/2016/26978604-Philip A. Clayton, Stephen P. McDonald, Graeme R. Russ, Steven J. Chadban ,Long-Term Outcomes after Acute Rejection in Kidney Transplant Recipients: An ANZDATA Analysis ,JASN Sep 2019, 30 (9) 1697-1707; DOI: 10.1681/ASN.2018111101
In recent decades there is significant reduction in the incidence of AR in particular TCMR due to better immunologic matching of donor and recipients, more potent induction as well as maintenance immunosuppressive agents, however acute rejection in the first 6 months still can impact the graft survivalespcialy in sensitazed recpients and this depending on many factors like the time ,type of rejection and severity of AR based on Banff histological classification.
The type of acute rejection:
1- pure acute T -cell mediated rejection, (TCMR) which limited to tubular inflammatory cells infiltration (Lymphocytes T-cells,)tubulitis and interstitial mononuclear cells infiltration with or without vascular injury ( endothelitis ), sever TCMR with vascular injury even with in 6 months can impact the graft survival , Steroid responsive TCMR usually have favor prognosis and outcome especially in the absence of significant chronic histological findings like IFTA, vascular intimal sclerosis, arteriolar hyaline thickening or frank necrosis those with vascular injury and steroid nonresponsive preferred to be treated with ATGs with augmentation of maintenance IS (tacrolimus, MMF, steroid).
2-ABMR with typical PTC – C4D staining and peritubular capillaritis (neutrophiles infiltrations), glomerulitis with GC ,also vascular injury with endothelitis plus serological evidence of DSAs, the concept of C4D negative ABMR should be consider in patients with histological finding suggestive of ABMR and positive serology for DSAs, and this can be explained by complement independent binding of DSAs AB to endothelial cells .ABMR may present as only as ATN in the context of acute graft dysfunction, endothelial linear C4D staining is highly suggestive of ABMR, especially in sensitized recipient ,ABMR carry poor prognosis compared to TCMR Graft and patient survival were worse in those who experienced rejection in the first 6 months post-transplant, particularly for those who experienced AMR. P,0.001(3).
3- Mixed type of rejection ,both acute cellular and ABMR can coexist and with vascular injury carry poor prognosis and impact the graft survival even with aggressive treatment, sometimes difficult to differentiate between the ABMR and sever TCMR especially in the presence of ATN with vascular injury (intimal arteritis), ABMR carry the risk of recurrence of rejection and /or progress to chronic graft injury with IFTA and chronic allograft nephropathy (CAN).
other factors that impact the outcome of acute rejection including the DSAs level, type, and the degree of sensitization, also type of donor? DD with EDC, DGF.
One study of 687 transplant recipients at one U.K. center in 1984 to 1996 defined “early” AR as occurring within 90 days of transplantation and “later” AR as any AR event from 91 days out to a maximum of 14 years (7). Five-year graft survival rates were 87% in patients without AR, 63% in those with “early” AR, and 45% in those with “late” AR
increased graft loss risk associated with late AR is likely mediated by multiple factors
late AR is more of AB mediated and carry poor prognosis (1,2) as clinical monitoring is less intense in the later period , patient follow up every 2-3 months so late AR can be diagnosed late with more sever and chronic graft damage and less treatable at time of diagnosis(1).
Type of HLA mismatch:
HLA class II mismatches have been associated with early AR, while class I mismatches have been associated with late AR, suggesting roles of direct and indirect allorecognition pathways in the pathophysiology of early AR and late AR.
References:
1-un-Q, Liu ZH, Ji S, et al. Late and early C4d-positive acute rejection: different clinico-histopathological subentities in renal transplantation. Kidney Int 2006; 70: 377.
2- the Implications of Acute Rejection for Allograft Survival in Contemporary U.S. Kidney Transplantation
Lentine, Krista L.1,5; Gheorghian, Adrian1; Axelrod, David2; Kalsekar, Anu3; L’italien, Gilbert3,4; Schnitzler, Mark A.1
3- up to date, kidney transplant in adult treatment of acuteT cell-mediated (cellular) rejection of renal allograft.
Acute rejection was defined clinically by an acute deterioration in allograft function and confirmed with tissue diagnosis. Banff borderline AR was not considered as an AR episode.
It has been demonstrated that an acute rejection (AR) episode is a major risk factor of graft loss.
Effect of ACUTE REJECTION;
not all rejection episodes have the same effect. Severity of rejection, described using the Banff system, timing of rejection as early (EAR) or late acute rejection (LAR), and whether the allograft recovers to the baseline function after rejection
all these variables affect the long-term graft outcome.
difference between EAR and LAR in impact on long-term graft survival.
Some studies have suggested that LAR has a poorer effect on long-term graft survival than EAR and recent studies showed that EAR was not the cause of graft failure 1.
It has been proposed that differences in immunologic activity and triggering factors such as infection or nonadherence to immunosuppressive medication may be the reasons for these distinctions 1.
A study by Eun Hee et al.on 709 patients Of these, 198 (28%) had biopsy-proven AR, 152 (21%) had EAR, 46 (7%) had LAR, and 511 (72%) did not have a rejection episode.
Allograft failure occurred in 65 patients. The 5-year graft survival rates were 97%, 89%, and 85% for patients with no AR, EAR, and LAR, respectively .
The graft survival rates were not different between the EAR group and LAR group 2.
Recently, El Ters et al showed that early acute cellular rejection was not a single acute event but triggered a persistent alloimmune response that might result in long-term graft injury and graft loss years after the acute event 3.
Acute rejection histologic types are
ABMR OR TCMR or mixed type.
Greater histologic severity of cellular AR has been associated with inferior death-censored graft survival.
Vascular AR in particular has been strongly associated with premature graft failure and histologically with premature development of chronic allograft nephropathy (CAN) in protocol biopsies.
Antibody-mediated rejection (AMR), particularly when vascular involvement is evident, incurs a high risk of graft failure over the ensuing 5 years.
mean serum creatinine at 12 months post-transplant was significantly higher among those with versus without AR suggested a degree of graft injury that may predispose to CAN.
Treatment for AR with high-dose steroids and/or lymphocyte-depleting antibodies incurs an increased risk of sepsis and cancer, potentially leading to death with a functioning graft.
Inferior graft function, proteinuria, and increased immunosuppression may also heighten cardiovascular risk, thereby predisposing affected recipients to cardiovascular morbidity and mortality.
Vascular AR is typically treated more aggressively than nonvascular rejection and may incur greater risks of both permanent graft damage and treatment-emergent adverse effects 4.
In comparison to those with AR without evidence of AMR, those with AMR experienced progressively higher rates of both graft loss and death over time, becoming evident beyond 5 years post-transplant
Lower eGFR and albuminuria are recognized as independent risk factors for all-cause and cardiovascular mortality in the general and kidney transplant populations and both may occur consequent to AR 4.
The intensity of immunosuppression may affect both cardiovascular risk, through mechanisms including development of new-onset diabetes, hypertension, dyslipidemia, renal impairment and proteinuria,and cancer risk.
AR was associated with significant increases in CAN, the leading causes of transplant failure in the current era. The associations noted were strongest for those with AMR and for those where initial therapy failed to enable return to baseline serum creatinine 4.
1 Sellares J, de Freitas DG, Mengel M, Reeve J, Einecke G, Sis B, Hidalgo LG, Famulski K, Matas A, Halloran PF. Understanding the causes of kidney transplant failure: the dominant role of antibody-mediated rejection and nonadherence. Am J Transplant. 2012;12:388–399.
2 Eun Hee Koo, Hye Ryoun Jang,The impact of early and late acute rejection on graft survival in renal transplantation.Kidney Res Clin Pract. 2015 Sep; 34(3): 160–164.
3 El Ters M, Grande JP, Keddis MT, Rodrigo E, Chopra B, Dean PG, Stegall MD, Cosio FG. Kidney allograft survival after acute rejection, the value of follow-up biopsies. Am J Transplant. 2013;13:2334–2341.
4 Philip A. Clayton, Stephen P. McDonald, Graeme R. Russ and Steven J. Chadban.Long-Term Outcomes after Acute Rejection in Kidney Transplant Recipients: An ANZDATA Analysis.JASN September 2019, 30 (9) 1697-1707.
Excellent Shereen
What is the effect of early acute rejection (within the first 6 months after transplantation) on graft survival?
Post renal transplant acute rejection episodes have decreased in current immunosuppressive era. Nonetheless, the effect of these rejections has been shown to reduce long-term graft survival. (1)
Early acute rejection is associated increased risk of recurrent acute rejections and increased risk of graft loss due to chronic allograft nephropathy. (1,2)
Opelz et al, in their study, showed that the risk of graft loss in a patient with acute rejection within first 3 months and 3-6 months post transplant is 35 % and 105% more as compared to someone who did not face any acute rejection episode. (2) This was more pronounced in those who did not respond fully to the treatment of acute rejection.
Tiers at al, in their analysis of graft biopsies, concluded that graft survival was poorer in only those patients with acute rejection who had abnormal histological changes post rejection. (3)
Ragheb et al, in their study showed that acute rejection is associated with poorer graft survival, but there was no difference in graft survival in early and late rejection group. (4)
Jalazadeh et al also showed that acute rejection episodes are associated with poorer graft survival, but more so in patients with late acute rejection. (5)
References:
1) Clayton PA, McDonald SP, Russ GR, et al. Long-Term Outcomes after Acute Rejection in Kidney Transplant Recipients: An ANZDATA Analysis. JASN 2019;30:1697-1707.
2) Opelz G, Dohler B. Influence of Time of Rejection on Long-Term Graft Survival in Renal Transplantation. Transplantation 2008;85:661-666.
3) Tiers ME, Grande JP, Keddis MT, et al. Kidney Allograft Survival After Acute Rejection,
the Value of Follow-Up Biopsies. Am J Transplant 2013;13:2334-2341.
4) Ragheb A, Kora MAE, Hassan YF, et al. Study of the effect of early and late acute rejection episodes on renal graft survival. J Egypt Soc Nephrol Transplant 2021;21:98-105.
5) Jalazadeh M, Mousavinasab N, Peyrovi S, et al. The Impact of Acute Rejection in Kidney Transplantation on Long-Term Allograft and Patient Outcome. Nephro Urol MOn 2015;7:e24439.
You need to elaborate more on :
type of rejection
predisposing factors related to patient as sensitisation
outcome of the episode
just needs work and relation to practice
Early Acute Rejection may be either T cell mediated rejection, or ABMR or a combination of both.
Early T cell mediated rejection with Banff I/IIa have excellent graft survival usually (due to increased steroid-responsiveness). Higher Banff TCMR have poorer graft survival. Similarly, Early AMR, if treated promptly, has better graft survival; but if not treated, may lead to chronic ABMR and graft loss. (1)
Presence of pre-existing antibodies are responsible for early AMR, hence the role of meticulous pre-transplant evaluation.
Reference:
1) Schinstock CA, Manno RB, Budde K, et al. Recommended Treatment for Antibody-mediated Rejection After Kidney Transplantation: The 2019 Expert Consensus From the Transplantation Society Working Group. Transplantation 2020;104:911-922.
Thanks Amit for your hard work
I will add to Prof Belal question
Do you think that all early acute rejection is associated with poor graft survival?
What about late acute rejection?
acute late rejection associated with poor outcome as its likely antibody mediated rejection and also due to late recognition with more chronic graft injury and less responsive to treatment.
reference:
the Implications of Acute Rejection for Allograft Survival in Contemporary U.S. Kidney Transplantation
Lentine, Krista L.1,5; Gheorghian, Adrian1; Axelrod, David2; Kalsekar, Anu3; L’italien, Gilbert3,4; Schnitzler, Mark A.1
Do you think that all early acute rejection is associated with poor graft survival?
No.
Early Acute Rejection may be either T cell mediated rejection, or ABMR or a combination of both.
Early T cell mediated rejection with Banff I/IIa have excellent graft survival usually. Higher Banff TCMR have poorer graft survival. Similarly, Early AMR, if treated promptly, has better graft survival; but if not treated, may lead to chronic ABMR and graft loss. (1)
What about late acute rejection?
Late acute rejections are a consequence of under-immunosuppression, non-adherence, infections and formation of de-novo DSAs. These, as compared to early acute rejections have been shown to have poorer graft outcomes and are associated with class I MHC incompatibility.
Reference:
1) Schinstock CA, Manno RB, Budde K, et al. Recommended Treatment for Antibody-mediated Rejection After Kidney Transplantation: The 2019 Expert Consensus From the Transplantation Society Working Group. Transplantation 2020;104:911-922.
2) Sijpkens YW, Doxiadis IIN, Mallat MJK, et al. Early versus late acute rejection episodes in renal transplantation. Transplantation 2003;75:204-208.
Episodes of acute rejection whether it is early or late are generally associated with poor graft survival but not all episodes are associated with the same impact on the kidney,
This may depend on some factors: [1,2]
REFERANCES
1. Opelz G, Döhler B, Collaborative Transplant Study Report. Influence of time of rejection on long-term graft survival in renal transplantation. Transplantation 2008; 85:661.
2. Madden RL, Mulhern JG, Benedetto BJ, et al. Completely reversed acute rejection is not a significant risk factor for the development of chronic rejection in renal allograft recipients. Transpl Int 2000; 13:344.
what aboute the type of rejection.
monitoring of both patient and graft
InABMR for example level of DSA.
This is a structured answer, but you need to add explantation Sherif
Episodes of EAR was reported by several studies to be more benign than episodes of LAR this may be explained by the lower incidence and severity of ABMR which is associated with lower graft survival, Moreover attacks of TCMR are usually mild responding well to corticosteroids
This may be explained by the following :
So … early AR episodes are usually mild ABMR, TCMR or subclinical rejection
Definition of Acute rejection (AR):
AR defined clinically by an acute deterioration in allograft function and confirmed with tissue diagnosis.
There are two principal histologic forms of acute rejection:
–Acute T cell-mediated rejection (TCMR)
-Active (acute) antibody-mediated rejection (ABMR) or mixed form of ABMR and TCMR
Banff borderline AR was not considered as an AR episode.
The emergence of calcineurin inhibitors and antiproliferative agents dramatically lowered the incidence of acute rejection.
Vascular AR has been strongly associated with premature graft failure and histologically with premature development of chronic allograft nephropathy (CAN) in subsequent protocol biopsies.
Antibody-mediated rejection (AMR), especially when vascular involvement is evident, carrying a high risk of graft failure over the next 5 years.
Acute rejection (AR) episode is a major risk factor of graft loss. But not all rejection episodes have the same effect it depends on:
Severity of rejection, timing of rejection as early or late acute rejection, and whether the allograft recovers to the baseline function after rejection all these factors can affect the long term graft outcome.
Some studies have suggested that late acute rejection has a poorer effect on long-term graft survival than Early acute rejection. It depends on immunologic activity and triggering factors such as infection or nonadherence to immunosuppressive medication may be the reasons for these differences between EAR and LAR.
The Causes of increased graft loss subsequent to AR may be due to:
-The degree of graft injury that may predispose to chronic allograft nephropathy (CAN)
-The cellular AR may be predisposed for donor-specific antibody development and subsequent AMR.
References:
Wu K, Budde K, Lu H, Schmidt D, Liefeldt L, Glander P, et al.: The severity of acute cellular rejection defined by Banff classification is associated with kidney allograft outcomes. Transplantation 97: 1146–1154, 2014
Nankivell BJ, Borrows RJ, Fung CL, O’Connell PJ, Allen RD, Chapman JR: The natural history of chronic allograft nephropathy. N Engl J Med 349: 2326–2333, 2003
welldone
What about the the prognosis of early steroid sensitive and mild ACR?
Are they associated with poor prognosis?
I think it is not associated with poor graft prognosis in mild steroid responsive TCMR ,in contrary with vascular rejection which is the severe form and can predispose for donor-specific antibody development and subsequent AMR.
The major cause of graft failure is AR, but not every episode of rejection had similar effect on graft. There are several factors increase the risk of AR & subsequently graft injury & loss, these factors include:
In general the rejection can occur due to:
Several studies show that EAR did not have an impact on graft & patients long term prognosis, but Ei Ters et al report that a single episode of acute cellular rejection can cause persistent allo immune response that may end with graft injury & loss.
There are conflict between the result of studies about the effect of EAR on graft outcome & this variability in results may be due to :
Resent studies show that EAR has a sequel reflected on patient & graft outcome beyond first 6 months after transplantation & EAR is associated more with male sex, HLA mismatch & older donor.
References:
welldone
What about the the prognosis of early steroid sensitive and mild ACR?
Are they associated with poor prognosis?
Over the past 2 decades, the number of acute allograft rejections has declined, in particular after the results of SYMPHONY trial, after which, the maintenance therapy in most transplant centers have been standardized as triple therapy including CNI/MMF/steroids.
Despite that, development of acute rejection carries a significant risk of graft loss during the first year following transplantation. As is acute rejection, subclinical rejection with IF/TA is an independent risk of allograft failure.
The definitions of early and late rejections vary between studies, so the cutoff of 6 months is not standardized. Most of studies report early rejection of days to months in timing, and late more than one year.
Several studies had demonstrated a strong link between early rejection and allograft dysfunction and failure in the subsequent 2–5 years. However, not all rejection episodes have the same allograft outcome. The long term graft outcome is affected by the severity of rejection, clinically and histologically, according to Banff criteria, timing of rejection Early vs Late acute rejection , and whether the allograft recovers to the baseline function after rejection.
In some studies, chronic allograft nephropathy was attributed to the development of early acute rejection. Recipients with early rejection had higher risk to develop cardiovascular complications or cancer. Early rejection is associated with significant long-term effects.
Other studies demonstrated that the occurrence of acute rejection was associated with an increased risk of graft loss after 6 months whereas ,late rejection was associated with higher risk of graft loss. The occurrence of acute rejection is associated with an ongoing increased risk of graft loss, particularly if that episode occurred late or included vascular rejection.
Finally, early and late acute rejections affect long-term graft survival. However most of the studies and most recent showed early rejection had poorer graft survival.
References
-Lefaucheur C, Loupy A, Vernerey D, Duong-Van-Huyen J-P, Suberbielle C, Anglicheau D, et al.: Antibody-mediated vascular rejection of kidney allografts: A population-based study. Lancet 381: 313–319, 2013
-El Ters M, Grande JP, Keddis MT, Rodrigo E, Chopra B, Dean PG, et al.: Kidney allograft survival after acute rejection, the value of follow-up biopsies. Am J Transplant 13: 2334–2341, 2013
-Wu K, Budde K, Lu H, Schmidt D, Liefeldt L, Glander P, et al.: The severity of acute cellular rejection defined by Banff classification is associated with kidney allograft outcomes. Transplantation 97: 1146–1154, 2014.
-Philip A. Clayton, Stephen P. McDonald, Graeme R. Russ, and Steven J. Chadban. Long-Term Outcomes after Acute Rejection in Kidney Transplant Recipients: An ANZDATA Analysis. JASN 30: 1697–1707, 2019
-McDonald S, Russ G, Campbell S, Chadban S: Kidney transplant rejection in Australia and New Zealand: Relationships between rejection and graft outcome. Am J Transplant 7: 1201–1208, 2007
welldone
Effect of early acute rejection (within the first 6 months after transplantation) on graft survival:
Advances in immunosuppression after kidney transplantation have decreased the influence of early acute rejection (EAR) on graft survival. Several studies have suggested that late acute rejection (LAR) has a poorer effect on long-term graft survival than EAR.
In a prospective study of 709 patients, 198 (30%) had biopsy-proven AR [EAR=152 patients (77%); LAR=46 patients (23%)]. A total of 65 transplants were lost. The 5-year graft survival rates were 97%, 89%, and 85% for patients with no AR, EAR, and LAR, respectively. These differences were significant (P<0.001 for both by log-rank test). In time-dependent Cox regression analysis, EAR (hazards ratio, 3.37; 95% confidence interval, 1.90–5.99) and LAR (hazards ratio, 5.32; 95% confidence interval, 2.65–10.69) were significantly related to graft failure. When we set LAR as standard and compared it with EAR, there was no statistical difference between EAR and LAR (P=0.21).
Kidney Res Clin Pract. 2015 Sep; 34(3): 160–164.
Published online 2015 Jul 26. doi: 10.1016/j.krcp.2015.06.003 PMCID: PMC4608868 PMID: 26484041
The impact of early and late acute rejection on graft survival in renal transplantation
Eun Hee Koo,1 Hye Ryoun Jang,1 Jung Eun Lee,1 Jae Berm Park,2 Sung-Joo Kim,2 Dae Joong Kim,1 Yoon-Goo Kim,1 Ha Young Oh,1 and Wooseong Huh1
Eun Hee Koo et al Study ;
1/ Effect of early acute rejection (within the first 6 months after transplantation) on graft survival:
2/ Risk profile of EAR and LAR
3/ Graft failure risk factor
In Eun Hee Koo et al Study ;
Thankyou Assafi for the detailed study review on your part can you please mention your own coclusions.
The incidence of acute rejection has fallen throughout the history of kidney transplantation to around 10-20% as reported by the major registries.
Early acute rejection was found to be associated with HLA-DR mismatch and delayed graft function and lead to graft failure due to chronic allograft nephropathy and recurrent acute rejection.
The diagnosis of acute rejection may have short term consequences beyond immediate graft loss. From a patient perspective, anxiety and fear of graft loss, increased tests and cost, follow up frequency, treatment intensity, and risk of side effects including infections and death.
Early episodes of acute rejection may also have consequences for the patients and their grafts beyond the 1st 6 months after transplantation. Greater histological severity of cellular acute rejection has been associated with inferior death-censored graft survival. Vascular acute rejection is strongly associated with premature graft failure and the development of chronic allograft nephropathy. ABMR particularly when vascular involvement is evident, represents a high risk of graft failure in the coming 5 years.
Recipients with early acute rejection also more likely to die from cardiovascular diseases or cancer.
Reference:
Clayton Ph.A., McDonald S.P.,Russ G.R., Chadban S.J. Long-Term Outcomes after Acute Rejection in Kidney Transplant Recipients: An ANZDATA Analysis. JASN( 2019) 30: 1697–1707.
Thanks, Huda
Yes, not every acute rejection is associated with a worse prognosis. Which acute rejection would not affect the prognosis?
I guess steroid responsive acute cellular rejection
Acute rejection either early or late will affect graft survival.
Definitions:
Acute rejection is defined as acute deterioration of graft function and proved with tissue diagnosis (diagnostic biopsy).
Graft failure defined as graft nephrectomy or retransplantation or return back to chronic dialysis.
DGF is defined as need of dialysis in the 1st week posttransplant.
Graft survival is lower in the patient with acute rejection either early or late than those with the patients with no rejection. Some studies suggested that there is no difference between early and late rejection on graft survival.
There are some factors may be related to early acute rejection (EAR) like HLA mismatch, male sex , living donor, old donor age , short ischemic time. Other factors may be related to late acute rejection (LAR) like young age, and positive PRA.
Both EAR and LAR affect negatively graft survival but no significant difference between both of them.
Some studies found significant impact of EAR on graft survival than LAR, some studies found the contrast.
So, both have a negative impact on survival either early or late.
Eun Hee Koo, Hye Ryoun Jang, Jung Eun Lee, Jae Berm Park, Sung-Joo Kim. The impact of early and late acute rejection on graft survival in renal transplantation. Kidney Research and Clinical Practice. Volume 34, Issue 3, September 2015, Pages 160-164
Some acute rejections do not affect the outcome. Do you know what are these types?
Reports about the impact of Early Acute Rejection are inconsistent. The reason for variable results might be that each study used different methods and populations, with the cutoff for EAR being particularly variable. Some studies used a 3-month cutoff to divide EAR and LAR [1,3]. Others used 6- or 12-month cutoffs [7,8]. Most studies categorized EAR and LAR by the onset of the first AR [1,2]. One study used the timing of the last treated AR [3]. Definitions of AR were also inconsistent. Some studies included AR diagnosed using clinical biopsy or using either clinical or protocol biopsy [5]. Others used clinical AR that was not biopsy proven [3,7]. Study populations also differed; some studies selected only deceased-donor kidney transplants [1-3], whereas others enrolled both living- and deceased-donor kidney transplants [5,6].
1. Joseph JT, Kingsmore DB, Junor BJ, Briggs JD, Mun Woo Y, Jaques BC, Hamilton DN, Jardine AG, Jindal RM. The impact of late acute rejection after cadaveric kidney transplantation. Clin Transplant 15:2001;221-227.
2. Opelz G, Dohler B. Influence of time of rejection on long-term graft survival in renal transplantation. Transplantation 85:2008;661-666.
3. Sijpkens YW, Doxiadis II, Mallat MJ, de Fijter JW, Bruijn JA, Claas FH, Paul LC. Early versus late acute rejection episodes in renal transplantation. Transplantation 75:2003;204-208.
4. Famulski KS, Einecke G, Sis B, Mengel M, Hidalgo LG, Kaplan B, Halloran PF. Defining the canonical form of T-cell-mediated rejection in human kidney transplants. Am J Transplant 10:2010;810-820.
5. Sellares J, de Freitas DG, Mengel M, Reeve J, Einecke G, Sis B, Hidalgo LG, Famulski K, Matas A, Halloran PF. Understanding the causes of kidney transplant failure: the dominant role of antibody-mediated rejection and nonadherence. Am J Transplant 12:2012;388-399.
6. El Ters M, Grande JP, Keddis MT, Rodrigo E, Chopra B, Dean PG, Stegall MD, Cosio FG. Kidney allograft survival after acute rejection, the value of follow-up biopsies. Am J Transplant 13:2013;2334-2341.
7. Lentine KL, Gheorghian A, Axelrod D, Kalsekar A, L’Italien G, Schnitzler MA. The implications of acute rejection for allograft survival in contemporary U.S. kidney transplantation. Transplantation 94:2012;369-376.
8. Sun Q, Liu ZH, Ji S, Chen J, Tang Z, Zeng C, Zheng C, Li LS. Late and early C4d-positive acute rejection: different clinico-histopathological subentities in renal transplantation. Kidney Int 70:2006;377-383.
Acute Rejection, regardless of its timing, significantly worsened graft survival. Treatments to reduce the incidence of AR and improve prognosis are needed.
The impact of early and late acute rejection on graft survival in renal transplantation
Eun Hee Koo et al