title: The Spectrum of Renal Allograft Failure.
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%).
  
  
  CONCLUSIONS
  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.affiliation: 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.
authors.forename: Sourabh
authors.initials: S
authors.lastname: Chand
authors.affiliation: Histocompatibility and Immunogenetics Laboratory, NHSBT Birmingham Centre, Vincent Drive, Edgbaston, Birmingham, United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Atkinson
authors.affiliation: Histocompatibility and Immunogenetics Laboratory, NHSBT Birmingham Centre, Vincent Drive, Edgbaston, Birmingham, United Kingdom.
authors.forename: Clare
authors.initials: C
authors.lastname: Collins
authors.affiliation: Histocompatibility and Immunogenetics Laboratory, NHSBT Birmingham Centre, Vincent Drive, Edgbaston, Birmingham, United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Briggs
authors.affiliation: Department of Nephrology and Kidney Transplantation, Queen Elizabeth Hospital, Birmingham, United Kingdom.|Centre for Translational Inflammation Research, University of Birmingham, Birmingham, United Kingdom.
authors.forename: Simon
authors.initials: S
authors.lastname: Ball
authors.affiliation: Department of Nephrology and Kidney Transplantation, Queen Elizabeth Hospital, Birmingham, United Kingdom.|Centre for Translational Inflammation Research, University of Birmingham, Birmingham, United Kingdom.
authors.forename: Adnan
authors.initials: A
authors.lastname: Sharif
authors.affiliation: Department of Renal Histopathology, Queen Elizabeth Hospital, Birmingham, United Kingdom.
authors.forename: Kassiani
authors.initials: K
authors.lastname: Skordilis
authors.affiliation: Department of Renal Histopathology, Queen Elizabeth Hospital, Birmingham, United Kingdom.
authors.forename: Bindu
authors.initials: B
authors.lastname: Vydianath
authors.affiliation: Department of Renal Histopathology, Queen Elizabeth Hospital, Birmingham, United Kingdom.
authors.forename: Desley
authors.initials: D
authors.lastname: Neil
authors.affiliation: Department of Nephrology and Kidney Transplantation, Queen Elizabeth Hospital, Birmingham, United Kingdom.|Centre for Translational Inflammation Research, University of Birmingham, Birmingham, United Kingdom.
authors.forename: Richard
authors.initials: R
authors.lastname: Borrows
mesh_terms: D000328:Adult; D000906:Antibodies / Q000276:immunology; D015922:Complement C1q / Q000276:immunology; D005260:Female; D005355:Fibrosis; D006084:Graft Rejection / Q000209:etiology* / Q000276:immunology / Q000473:pathology*; D006648:Histocompatibility; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D007668:Kidney / Q000276:immunology / Q000473:pathology*; D016030:Kidney Transplantation / Q000379:methods; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: D000906:Antibodies; D000949:Histocompatibility Antigens Class II; D015922:Complement C1q