Clinicopathological Analysis of Acute/Active Antibody-Mediated Rejection in Renal Allografts According to the Banff 2013 Classification

Abstract

Aim: This study evaluated the clinicopathological findings of acute/active antibody-mediated rejection (AABMR) according to the Banff 2013 classification.

Methods: We analyzed 345 biopsies of 269 kidney transplant recipients. Pathological AABMR (PAABMR) was defined as histological evidence of acute tissue injury and endothelial injury by light microscopy regardless of donor-specific antibodies (DSAs).

Results: Among the 345 biopsies, 29 (8.4%) were diagnosed as PAABMR. The mean g score was 1.17 ± 0.60, the mean ptc score was 1.97 ± 1.32, and DSA positivity was found in 69% of PAABMR. The mean duration after transplantation was 22.9 ± 26.7 months. Among 3 groups (DSA-high, mean fluorescence intensity (MFI) ≥ 5,000; DSA-low, MFI < 5,000 to ≥1,000; below cutoff), ABO incompatibility in DSA-high was significantly lower and second transplantation in DSA-high was significantly higher. We found 83% of PAABMR by the protocol biopsy (subclinical AABMR [SAABMR]). The short-term clinical and light microscopical changes in 8 cases of SAABMR did not show worsening during follow-up period (9-24 months). However, ultrastructural finding, including glomerular endothelial swelling, subendothelial electron-lucent widening, and early glomerular basement duplication, were found by electron microscopy (EM) in the first biopsies, and half of the SAABMR cases developed de novo circular peritubular capillary multilayering in the follow-up biopsies.

Conclusion: PAABMR was mainly found by the protocol biopsy. The short-term follow-up of SAABMR patients did not show worsening clinically and light microscopically, but ultrastructural examination by EM was useful to detect early lesions of endothelial injury and progression of glomerular and peritubular capillary basement membrane alterations.

Keywords: Acute/active antibody-mediated rejection; Allograft; Banff 2013 classification; Electron microscopy; Kidney transplantation.

Fig. 1

Representative images evaluated by EM show glomerular endothelial cell swelling (a), subendothelial electron-lucent widening (b), early duplication/multilayering of the GBM (c), and early PTCBM multilayering (d, e). EM, electron microscopy; GBM, glomerular basement membrane; PTCBM, peritubular capillary basement membrane.

Fig. 2

Histological change of SAABMR as evaluated by LM. The Banff g score (a), ptc score (b), C4d score (c), ct score (d), and ci score showed no significant change between the diagnosis of SAABMR and the follow-up biopsy (e). SAABMR, subclinical acute/active antibody-mediated rejection; LM, light microscopy.

Fig. 3

Histological change of SAABMR evaluated by EM. Prevalences of glomerular endothelial cell swelling (a), subendothelial electron-lucent widening (b), early duplication of GBM (c), and partial PTCBM and circumferential PTCBM multilayering (d). SAABMR, subclinical acute/active antibody-mediated rejection; EM, electron microscopy; GBM, glomerular basement membrane; PTCBM, peritubular capillary basement membrane.