Association of angiotensin II type 1 receptor antibodies with graft histology, function and survival in paediatric renal transplant recipients. Issue 6 (12th February 2018)

• Record Type: Journal Article
• Authors: Fichtner, Alexander; Süsal, Caner; Schröder, Claudia; Höcker, Britta; Rieger, Susanne; Waldherr, Rüdiger; Westhoff, Jens H; Sander, Anja; Dragun, Duska; Tönshoff, Burkhard
• Is Part Of: Nephrology dialysis transplantation. Volume 33:Issue 6(2018)
• Page Start: 1065
• Page End: 1072
• Publication Date: 2018-02-12
• Subjects: angiotensin II type 1 receptor antibodies -- C1q-binding donor-specific antibodies -- donor-specific HLA antibodies -- graft failure -- indication biopsy -- paediatric renal transplantation; Nephrology -- Periodicals; Hemodialysis -- Periodicals; Kidneys -- Transplantation -- Periodicals; Hemodialysis; Kidneys -- Transplantation; Nephrology; Periodicals; 616.61
• DOI: 10.1093/ndt/gfy008
• Languages: English
• ISSNs: 0931-0509

Abstract

ABSTRACT: Background: We analysed in a carefully phenotyped cohort of paediatric patients the association of serum angiotensin II type 1 receptor antibodies (AT1 R-Ab) with specific histological lesions and with graft function and survival in conjunction with overall and complement-binding donor-specific human leucocyte antigen donor-specific antibodies (HLA-DSA). Methods: Sera of 62 patients at the time of renal graft biopsy for clinical indication >1 year post-transplant were assessed for AT1 R-Ab by enzyme-linked immunosorbent assay (ELISA) and for DSA and C1q-fixing DSA by single-antigen bead technology. Results: Serum AT1 R-Ab concentration was significantly higher in antibody-mediated rejection (ABMR) than in T-cell-mediated rejection or control. By receiver operating characteristic (ROC) curve analysis, the optimal AT1 R-Ab cut-off value discriminating between patients with features of ABMR and those without was 9.5 U/mL. A total of 6 of 28 patients (21.4%) with ABMR were only positive for AT1 R-Ab. Patients with AT1 R-Ab and HLA-DSA double positivity had a significantly higher vascular micro-inflammation score than DSA-negative patients. The 5-year graft survival was only 59% in the AT1 R-Ab-positive group compared with 87% in the AT1 R-Ab-negative group. Patients with AT1 R-Ab and HLA-DSA double positivity tended to have a more rapid decline of estimated glomerular filtration rate (eGFR) than patients who were only positive for AT1 R-Ab or HLA-DSA. In a multivariate Cox regression model of non-invasive factors, C1q-positive HLA-DSA, eGFR and AT1 R-Ab positivity were significantly associated with accelerated graft function decline. Conclusions: Serum AT1 R-Ab positivity in the context of an indication biopsy >1 year post-transplant is associated with the histopathology of ABMR and is an independent non-invasive risk factor for adverse graft outcome.