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Concurrent Antibody-Mediated Rejection in Post-Transplant IgA Nephropathy – Diagnosis Using a Stepwise Approach of Graft Morphology

Background Diagnosis of concurrent antibody-mediated rejection (AMR) is difficult in cases of post-transplant IgA nephropathy (TxIgAN) with glomerular inflammation. Glomerular inflammatory cell infiltration may be seen either in the contexts of AMR or immune complex-mediated injury and described as ‘glomerulitis’ (‘G’) or ‘endocapillary hypercellularity’ (‘E’), respectively. Methods We analyzed 40 renal allograft biopsy samples of 37 TxIgAN patients having glomerular inflammatory cells (‘E’ and/or ‘G’) between January 1992 and December 2016, in search for ancillary morphologic features in the diagnosis of concurrent AMR. Results Glomerular inflammation was described as ‘G’, ‘E’, or both in 11, 14, and 15 biopsies, respectively. Morphologic features supportive of acute and chronic AMR (AAMR and CAMR, respectively), comprising peritubular capillaritis, glomerular basement membrane doubling, peritubular capillary basement membrane multilayering, and peritubular capillary C4d staining, were sequentially examined, which revealed nine AAMR and 14 CAMR. C4d was positive in 77.8% of AAMR and 42.9% of CAMR. Of the remaining 17 biopsy samples without AMR, mesangial hypercellularity and/or crescents were present in 14 samples. In four samples, acute T cell-mediated rejection coexisted. Conclusions Diagnosis of concurrent AMR can be aided by using a stepwise approach of morphologic features of AMR in cases of TxIgAN with glomerular inflammation.