Antibody-Mediated Rejection in Kidney Transplantation: A Retrospective Study on the Impact of Donor-Specific Antibodies and on the Timing of Diagnosis

Introduction Limited information exists concerning the clinical significance of histologically confirmed antibody-mediated rejection (h-AMR) without detectable circulating donor-specific antibodies (DSA). In this study, we compared the outcomes of patients with h-AMR according to DSA status. Methods A total of 80 kidney transplant (KT) recipients who met the 2018 Banff criteria for h-AMR were included. Clinical and immunological characteristics were evaluated, and outcomes were compared according to DSA status after kidney biopsy (KB). Results There were 57 patients who had DSA-positive (+) h-AMR and 23 patients who had DSA-negative (-) h-AMR. Groups had similar baseline characteristics and time between KT and KB. Concerning histopathological diagnoses/Banff scores, DSA+ patients had higher interstitial fibrosis (ci) and tubular atrophy (ct) (ci+ct) scores and lower arterial hyalinosis (ah) scores compared to DSA- patients. Graft survival (GS) was similar for both groups (64% versus 44% at five years and 44% versus 34% at 10 years). Multivariate analysis revealed the time of KB (less than six months after KT or more than six months after KT) to be associated with GS. A stratified analysis was conducted, targeting DSA status according to the time of biopsy. For KB performed less than six months after KT, GS was higher for DSA+ patients at 10 years (66% versus 23%). For KB performed more than six months after KT, DSA- patients had higher GS at 10 years (58% versus 9%). Conclusion Both the timing of AMR diagnosis and DSA status had an impact on AMR outcomes. For patients diagnosed with AMR more than six months after transplantation, GS was worst for those in which circulating DSA were identified. Biopsy specimens from DSA- specimens had higher ct-ci and ah scores.

[1]  F. Claas,et al.  Association of HLA Mismatches and Histology Suggestive of Antibody-Mediated Injury in the Absence of Donor-Specific Anti-HLA Antibodies , 2022, Clinical journal of the American Society of Nephrology : CJASN.

[2]  J. Farber,et al.  Histologic Antibody-Mediated Kidney Allograft Rejection in the Absence of Donor Specific HLA Antibodies. , 2021, Transplantation.

[3]  E. Lerut,et al.  Risk factors, histopathological features and graft outcome of transplant glomerulopathy in the absence of donor-specific HLA antibodies. , 2021, Kidney international.

[4]  F. Claas,et al.  Eplet Mismatch Load and De Novo Occurrence of Donor-Specific Anti-HLA Antibodies, Rejection, and Graft Failure after Kidney Transplantation: An Observational Cohort Study. , 2020, Journal of the American Society of Nephrology : JASN.

[5]  J. Olivo-Marin,et al.  Transcriptional Changes in Kidney Allografts with Histology of Antibody-Mediated Rejection without Anti-HLA Donor-Specific Antibodies. , 2020, Journal of the American Society of Nephrology : JASN.

[6]  M. Stegall,et al.  The Banff 2019 Kidney Meeting Report (I): Updates on and clarification of criteria for T cell– and antibody‐mediated rejection , 2020, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[7]  B. Astor,et al.  Clinical Significance of Microvascular Inflammation in the Absence of Anti-HLA DSA in Kidney Transplantation. , 2019, Transplantation.

[8]  E. Lerut,et al.  Histological picture of antibody‐mediated rejection without donor‐specific anti‐HLA antibodies: Clinical presentation and implications for outcome , 2018, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[9]  A. Cabrita,et al.  Detection of Complement-binding Donor-specific Antibodies, Not IgG-antibody Strength Nor C4d Status, at Antibody-mediated Rejection Diagnosis Is an Independent Predictor of Kidney Graft Failure , 2018, Transplantation.

[10]  Jan U. Becker,et al.  A 2018 Reference Guide to the Banff Classification of Renal Allograft Pathology , 2018, Transplantation.

[11]  D. Roelen,et al.  Chronic‐active antibody‐mediated rejection with or without donor‐specific antibodies has similar histomorphology and clinical outcome – a retrospective study , 2018, Transplant international : official journal of the European Society for Organ Transplantation.

[12]  P. Aljama,et al.  Impact of Preformed Donor-Specific Anti-Human Leukocyte Antigen Antibody C1q-Binding Ability on Kidney Allograft Outcome , 2017, Front. Immunol..

[13]  M. Haas,et al.  The Revised (2013) Banff Classification for Antibody‐Mediated Rejection of Renal Allografts: Update, Difficulties, and Future Considerations , 2016, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[14]  P. Halloran,et al.  Identifying Subphenotypes of Antibody‐Mediated Rejection in Kidney Transplants , 2016, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[15]  T. Muthukumar,et al.  Development and validation of a prognostic index for allograft outcome in kidney recipients with transplant glomerulopathy , 2015, Kidney international.

[16]  W. Hanf,et al.  Transplant Glomerulopathy: The Interaction of HLA Antibodies and Endothelium , 2014, Journal of immunology research.

[17]  X. Jouven,et al.  Complement-binding anti-HLA antibodies and kidney-allograft survival. , 2013, The New England journal of medicine.

[18]  S. Allison Transplantation: Antibody-mediated vascular rejection of transplanted kidneys , 2013, Nature Reviews Nephrology.

[19]  P. Halloran,et al.  De Novo Donor‐Specific Antibody at the Time of Kidney Transplant Biopsy Associates with Microvascular Pathology and Late Graft Failure , 2009, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[20]  M. Stegall,et al.  Identifying Specific Causes of Kidney Allograft Loss , 2009, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[21]  M. Stegall,et al.  Transplant Glomerulopathy , 2008, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[22]  S. Dikman,et al.  Transplant glomerulopathy may occur in the absence of donor-specific antibody and C4d staining. , 2007, Clinical journal of the American Society of Nephrology : CJASN.

[23]  T. Larson,et al.  Transplant Glomerulopathy: Subclinical Incidence and Association with Alloantibody , 2007, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[24]  P. Dyer,et al.  Posttransplantation production of donor HLA-specific antibodies as a predictor of renal transplant outcome1 , 2003, Transplantation.