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The Spectrum of Renal Allograft Failure.
PLoS One. 2016; 11(9):e0162278.Plos

Abstract

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.

Authors+Show Affiliations

Department of Nephrology and Kidney Transplantation, Queen Elizabeth Hospital, Birmingham, United Kingdom. Centre for Translational Inflammation Research, University of Birmingham, Birmingham, United Kingdom. Renal Department, Royal Shrewsbury Hospital, Shropshire, United Kingdom.Histocompatibility and Immunogenetics Laboratory, NHSBT Birmingham Centre, Vincent Drive, Edgbaston, Birmingham, United Kingdom.Histocompatibility and Immunogenetics Laboratory, NHSBT Birmingham Centre, Vincent Drive, Edgbaston, Birmingham, United Kingdom.Histocompatibility and Immunogenetics Laboratory, NHSBT Birmingham Centre, Vincent Drive, Edgbaston, Birmingham, United Kingdom.Department of Nephrology and Kidney Transplantation, Queen Elizabeth Hospital, Birmingham, United Kingdom. Centre for Translational Inflammation Research, University of Birmingham, Birmingham, United Kingdom.Department of Nephrology and Kidney Transplantation, Queen Elizabeth Hospital, Birmingham, United Kingdom. Centre for Translational Inflammation Research, University of Birmingham, Birmingham, United Kingdom.Department of Renal Histopathology, Queen Elizabeth Hospital, Birmingham, United Kingdom.Department of Renal Histopathology, Queen Elizabeth Hospital, Birmingham, United Kingdom.Department of Renal Histopathology, Queen Elizabeth Hospital, Birmingham, United Kingdom.Department of Nephrology and Kidney Transplantation, Queen Elizabeth Hospital, Birmingham, United Kingdom. Centre for Translational Inflammation Research, University of Birmingham, Birmingham, United Kingdom.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27649571

Citation

Chand, Sourabh, et al. "The Spectrum of Renal Allograft Failure." PloS One, vol. 11, no. 9, 2016, pp. e0162278.
Chand S, Atkinson D, Collins C, et al. The Spectrum of Renal Allograft Failure. PLoS ONE. 2016;11(9):e0162278.
Chand, S., Atkinson, D., Collins, C., Briggs, D., Ball, S., Sharif, A., Skordilis, K., Vydianath, B., Neil, D., & Borrows, R. (2016). The Spectrum of Renal Allograft Failure. PloS One, 11(9), e0162278. https://doi.org/10.1371/journal.pone.0162278
Chand S, et al. The Spectrum of Renal Allograft Failure. PLoS ONE. 2016;11(9):e0162278. PubMed PMID: 27649571.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The Spectrum of Renal Allograft Failure. AU - Chand,Sourabh, AU - Atkinson,David, AU - Collins,Clare, AU - Briggs,David, AU - Ball,Simon, AU - Sharif,Adnan, AU - Skordilis,Kassiani, AU - Vydianath,Bindu, AU - Neil,Desley, AU - Borrows,Richard, Y1 - 2016/09/20/ PY - 2016/08/10/received PY - 2016/08/21/accepted PY - 2016/9/21/entrez PY - 2016/9/21/pubmed PY - 2017/8/12/medline SP - e0162278 EP - e0162278 JF - PloS one JO - PLoS ONE VL - 11 IS - 9 N2 - 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. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/27649571/The_Spectrum_of_Renal_Allograft_Failure_ L2 - http://dx.plos.org/10.1371/journal.pone.0162278 DB - PRIME DP - Unbound Medicine ER -