The Spectrum of Renal Allograft Failure.
BACKGROUND:Causes of "true" late kidney allograft failure remain unclear as study selection bias and limited follow-up risk incomplete representation of the spectrum. METHODS:We evaluated all unselected graft failures from 2008-2014 (n = 171; 0-36 years post-transplantation) by contemporar...
Main Authors: | , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2016-01-01
|
Series: | PLoS ONE |
Online Access: | http://europepmc.org/articles/PMC5029903?pdf=render |
id |
doaj-246ed5c2f13b48e2a3876c34a593fad9 |
---|---|
record_format |
Article |
spelling |
doaj-246ed5c2f13b48e2a3876c34a593fad92020-11-25T02:13:29ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01119e016227810.1371/journal.pone.0162278The Spectrum of Renal Allograft Failure.Sourabh ChandDavid AtkinsonClare CollinsDavid BriggsSimon BallAdnan SharifKassiani SkordilisBindu VydianathDesley NeilRichard BorrowsBACKGROUND:Causes of "true" late kidney allograft failure remain unclear as study selection bias and limited follow-up risk incomplete representation of the spectrum. METHODS:We evaluated all unselected graft failures from 2008-2014 (n = 171; 0-36 years post-transplantation) by contemporary classification of indication biopsies "proximate" to failure, DSA assessment, clinical and biochemical data. RESULTS:The spectrum of graft failure changed markedly depending on the timing of allograft failure. Failures within the first year were most commonly attributed to technical failure, acute rejection (with T-cell mediated rejection [TCMR] dominating antibody-mediated rejection [ABMR]). Failures beyond a year were increasingly dominated by ABMR and 'interstitial fibrosis with tubular atrophy' without rejection, infection or recurrent disease ("IFTA"). Cases of IFTA associated with inflammation in non-scarred areas (compared with no inflammation or inflammation solely within scarred regions) were more commonly associated with episodes of prior rejection, late rejection and nonadherence, pointing to an alloimmune aetiology. Nonadherence and late rejection were common in ABMR and TCMR, particularly Acute Active ABMR. Acute Active ABMR and nonadherence were associated with younger age, faster functional decline, and less hyalinosis on biopsy. Chronic and Chronic Active ABMR were more commonly associated with Class II DSA. C1q-binding DSA, detected in 33% of ABMR episodes, were associated with shorter time to graft failure. Most non-biopsied patients were DSA-negative (16/21; 76.1%). Finally, twelve losses to recurrent disease were seen (16%). CONCLUSION:This data from an unselected population identifies IFTA alongside ABMR as a very important cause of true late graft failure, with nonadherence-associated TCMR as a phenomenon in some patients. It highlights clinical and immunological characteristics of ABMR subgroups, and should inform clinical practice and individualised patient care.http://europepmc.org/articles/PMC5029903?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Sourabh Chand David Atkinson Clare Collins David Briggs Simon Ball Adnan Sharif Kassiani Skordilis Bindu Vydianath Desley Neil Richard Borrows |
spellingShingle |
Sourabh Chand David Atkinson Clare Collins David Briggs Simon Ball Adnan Sharif Kassiani Skordilis Bindu Vydianath Desley Neil Richard Borrows The Spectrum of Renal Allograft Failure. PLoS ONE |
author_facet |
Sourabh Chand David Atkinson Clare Collins David Briggs Simon Ball Adnan Sharif Kassiani Skordilis Bindu Vydianath Desley Neil Richard Borrows |
author_sort |
Sourabh Chand |
title |
The Spectrum of Renal Allograft Failure. |
title_short |
The Spectrum of Renal Allograft Failure. |
title_full |
The Spectrum of Renal Allograft Failure. |
title_fullStr |
The Spectrum of Renal Allograft Failure. |
title_full_unstemmed |
The Spectrum of Renal Allograft Failure. |
title_sort |
spectrum of renal allograft failure. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2016-01-01 |
description |
BACKGROUND:Causes of "true" late kidney allograft failure remain unclear as study selection bias and limited follow-up risk incomplete representation of the spectrum. METHODS:We evaluated all unselected graft failures from 2008-2014 (n = 171; 0-36 years post-transplantation) by contemporary classification of indication biopsies "proximate" to failure, DSA assessment, clinical and biochemical data. RESULTS:The spectrum of graft failure changed markedly depending on the timing of allograft failure. Failures within the first year were most commonly attributed to technical failure, acute rejection (with T-cell mediated rejection [TCMR] dominating antibody-mediated rejection [ABMR]). Failures beyond a year were increasingly dominated by ABMR and 'interstitial fibrosis with tubular atrophy' without rejection, infection or recurrent disease ("IFTA"). Cases of IFTA associated with inflammation in non-scarred areas (compared with no inflammation or inflammation solely within scarred regions) were more commonly associated with episodes of prior rejection, late rejection and nonadherence, pointing to an alloimmune aetiology. Nonadherence and late rejection were common in ABMR and TCMR, particularly Acute Active ABMR. Acute Active ABMR and nonadherence were associated with younger age, faster functional decline, and less hyalinosis on biopsy. Chronic and Chronic Active ABMR were more commonly associated with Class II DSA. C1q-binding DSA, detected in 33% of ABMR episodes, were associated with shorter time to graft failure. Most non-biopsied patients were DSA-negative (16/21; 76.1%). Finally, twelve losses to recurrent disease were seen (16%). CONCLUSION:This data from an unselected population identifies IFTA alongside ABMR as a very important cause of true late graft failure, with nonadherence-associated TCMR as a phenomenon in some patients. It highlights clinical and immunological characteristics of ABMR subgroups, and should inform clinical practice and individualised patient care. |
url |
http://europepmc.org/articles/PMC5029903?pdf=render |
work_keys_str_mv |
AT sourabhchand thespectrumofrenalallograftfailure AT davidatkinson thespectrumofrenalallograftfailure AT clarecollins thespectrumofrenalallograftfailure AT davidbriggs thespectrumofrenalallograftfailure AT simonball thespectrumofrenalallograftfailure AT adnansharif thespectrumofrenalallograftfailure AT kassianiskordilis thespectrumofrenalallograftfailure AT binduvydianath thespectrumofrenalallograftfailure AT desleyneil thespectrumofrenalallograftfailure AT richardborrows thespectrumofrenalallograftfailure AT sourabhchand spectrumofrenalallograftfailure AT davidatkinson spectrumofrenalallograftfailure AT clarecollins spectrumofrenalallograftfailure AT davidbriggs spectrumofrenalallograftfailure AT simonball spectrumofrenalallograftfailure AT adnansharif spectrumofrenalallograftfailure AT kassianiskordilis spectrumofrenalallograftfailure AT binduvydianath spectrumofrenalallograftfailure AT desleyneil spectrumofrenalallograftfailure AT richardborrows spectrumofrenalallograftfailure |
_version_ |
1724904858133200896 |