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- Title
Association of angiotensin II type 1 receptor antibodies with graft histology, function and survival in paediatric renal transplant recipients.
- Authors
Fichtner, Alexander; Süsal, Caner; Schröder, Claudia; Höcker, Britta; Rieger, Susanne; Waldherr, Rüdiger; Westhoff, Jens H; Sander, Anja; Dragun, Duska; Tönshoff, Burkhard
- Abstract
Background. We analysed in a carefully phenotyped cohort of paediatric patients the association of serum angiotensin II type 1 receptor antibodies (AT1R-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 AT1R-Ab by enzyme-linked immunosorbent assay (ELISA) and for DSA and C1q-fixing DSA by single-antigen bead technology. Results. Serum AT1R-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 AT1R-Ab cut-off value discriminating between patients with features of ABMR and those without was 9.5U/mL. A total of 6 of 28 patients (21.4%) with ABMR were only positive for AT1R-Ab. Patients with AT1R-Ab and HLADSA double positivity had a significantly higher vascular microinflammation score than DSA-negative patients. The 5-year graft survival was only 59% in the AT1R-Ab-positive group compared with 87% in the AT1R-Ab-negative group. Patients with AT1RAb 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 AT1R-Ab or HLA-DSA. In a multivariate Cox regression model of non-invasive factors, C1qpositive HLA-DSA, eGFR and AT1R-Ab positivity were significantly associated with accelerated graft function decline. Conclusions. Serum AT1R-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.
- Subjects
ANGIOTENSIN receptors; KIDNEY transplantation; PEDIATRIC surgery; HLA histocompatibility antigens; BLOOD serum analysis
- Publication
Nephrology Dialysis Transplantation, 2018, Vol 33, Issue 6, p1065
- ISSN
0931-0509
- Publication type
Article
- DOI
10.1093/ndt/gfy008