DSA presence does not affect renal histology and clinical outcome in chronic active antibody mediated rejection

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K.A. Sablik, M.C. Clahsen-van Groningen, C.W.N. Looman, J. Damman, D.L. Roelen, M. van Agteren, M.G.H. Betjes

Chair(s): dr. D.A. Hesselink

Thursday 9 march 2017

12:30 - 12:45h

Categories: Poster - Klinisch

Parallel session: Postersessie - Klinisch 1

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Chronic active antibody mediated rejection (caABMR) is a major cause of long term renal allograft dysfunction. It is defined by the presence of microvascular inflammation (MVI), histopathological changes compatible with transplant glomerulopathy (TG) and the presence of donor specific antibodies (DSA). Ongoing activation of endothelial cells by circulating DSA is associated with MVI and the subsequent development of TG. Although considered mandatory for the diagnosis of caABMR, it is not uncommon for TG with MVI  to present itself without detectable DSA. In this study we evaluated whether the presence or absence of  DSA  is associated with renal histology, allograft survival and response to therapy.

Forty-one biopsy-proven caABMR patients were included retrospectively between 2007 and 2014. All patients had progressive loss of allograft function and were treated similarly after diagnosis. DSA status was determined by single bead Luminex assay. Clinical characteristics, histomorphology, renal allograft function, response to therapy and allograft survival were compared between the DSA+ (N=17) and DSA- (N=24) caABMR patients. Possible variation in DSA detectability over time was assessed for the DSA- patients.

In all cases, DSA were de novo and the majority was directed against HLA-II being mostly anti-HLA-DQ antibodies. There were no statistically significant differences found in the clinical characteristics, renal allograft survival and histomorphologic lesions between patient groups. Both groups showed substantial and severe chronic histopathological damage and inflammation, consistent with caABMR. Decline in allograft function was similar without a statistically significant difference in treatment effect between the two groups (p=0.93).

However, C4d+DSA+ patients showed significantly poorer allograft function and better response to therapy prior to caABMR diagnosis when compared to C4d-DSA+ patients (p=0.01).

Conclusion. The presence or absence of detectable DSA has no significant association with renal histology and clinical outcome in caABMR patients. We did however find that, irrespective of DSA+, patients with caABMR and C4d+ in their biopsy responded better to therapy.