ESPN 50th Annual Meeting

ESPN 2017


 
Association of angiotensin II type 1 receptor antibodies with graft histology, function and survival in paediatric renal transplant recipients
FICHTNER ALEXANDER 1 SÜSAL CANER 2 SCHRÖDER CLAUDIA 1 HÖCKER BRITTA 1 RIEGER SUSANNE 1 WESTHOFF JENS 1 WALDHERR RÜDIGER 3 TÖNSHOFF BURKHARD 1

1- DEPARTMENT OF PEDIATRICS I, UNIVERSITY CHILDRENS HOSPITAL OF HEIDELBERG, GERMANY
2- TRANSPLANTATION IMMUNOLOGY, INSTITUTE OF IMMUNOLOGY, UNIVERSITY OF HEIDELBERG, GERMANY
3- INSTITUTE OF CLINICAL PATHOLOGY HEIDELBERG, GERMANY
 
Introduction:

 The predominant role of antibody-mediated rejections (ABMR) presupposing premature graft dysfunction is comprehensively described. The main causes are donor-specific HLA-antibodies (HLA-DSA). However, not all cases could be attributed to HLA-DSA. Therefore, we found it of interest to investigate the association of non-HLA angiotensin II type 1 receptor antibodies (AT1R-AB) with graft histology, function and survival.

Material and methods:

 62 patients with a low immunological risk profile and graft biopsies for clinical indication more than one year post-transplant were included. Serum samples at the time of indication biopsy were analysed for the presence of HLA-DSA and AT1R-AB. HLA-DSA with an MFI value > 500 were classified as positive (LABScreen Luminex Kits (One Lambda)). The cut-off value for AT1R-AB was defined as 10 U/mL (ELISA, CellTrend GmbH).  

Results:

32 of 62 patients (52%) were positive for AT1R-AB at the time of indication biopsy. After stratification according to different histologic entities, the ABMR positive group (including biopsies with suspected ABMR, BANFF’15) revealed significantly higher AT1R-AB levels compared to the group with T-cell mediated rejection or the group without rejection (median 12 vs. 9 or 8 U/mL; both comparisons p<0.05). Based on ROC-curve analyses, the optimal cut-off to differentiate between ABMR and non-ABMR biopsy results was 9.5 U/mL (ROC-AUC 0.74). AT1R-AB positivity (>9.5 U/mL) was associated with a significantly decreased graft survival 5 years post-biopsy (p=0.025). Furthermore, AT1R-AB positive patients more frequently reached the end-point ‘graft function deterioration’, defined as an eGFR-decline of more than 50% compared to baseline values before indication biopsy (p=0.004). Sub-classifying the antibody positive group by HLA-DSA and AT1R-AB status revealed no significant difference between the only AT1R-AB positive and the AT1R-AB/HLA-DSA double positive groups regarding graft function or graft survival. 

Conclusions:

 AT1R-AB positivity at the time of indication biopsy is associated with a significantly increased risk of graft function deterioration.