Clinical and pathological analyses of transplant glomerulopathy cases

Abstract

Aim: Transplant glomerulopathy (TG) is included as one of the criteria of chronic active antibody-mediated rejection (c-AMR) in Banff 09 classification. In this report, we discuss the clinical and pathological analyses of cases of TG after renal transplantation.

Patients: TG was diagnosed in 86 renal allograft biopsy specimens (BS) obtained from 50 renal transplant patients followed up at our institute between January 2006 and October 2012. We retrospectively reviewed the data of these 86 BS and 50 patients.

Results: Among the 50 patients, 42 (84%) had a history of acute rejection (AR); of these, 30 (60%) had acute antibody-mediated rejection (a-AMR). Among the 86 BS of TG, the TG was mild in 35 cases (cg1 in Banff classification), moderate in 28 cases (cg2) and severe in 23 cases (cg3). Peritubular capillaritis was present in 74 BS (86%), transplant glomerulitis in 65 (76%), interstitial fibrosis and tubular atrophy (IF/TA) in 71 (83%), thickening of the peritubular capillary (PTC) basement membrane in 72 (84%), and interstitial inflammation in 40 (47%). C4d deposition in the PTC was present in 49 BS (57%); 39 of these 49 BS showed diffuse C4d deposits in the PTC (C4d3), while the remaining 10 BS showed focal deposits (C4d2). Diffuse C4d deposition in the glomerular capillaries (GC) was seen in 70 BS (81%), while focal C4d deposition in the GC was seen in 9 (11%). In the assay using plastic beads coated with HLA antigen performed in 67 serum samples obtained in the peri-biopsy period, circulating ant-HLA alloantibody was detected in 55 (82%); in 33 of the 55 (49%) samples, donor-specific antibodies (DSA) were detected. Among our study, the findings in 22 BS (26%) fully met the criteria for c-AMR in Banff '09 classification, including TG, C4d deposition in the PTC and presence of DSA, while those in 27 BS were suspicious of c-AMR. Deterioration of the renal allograft function after the biopsies was seen in 31 patients (62%), of which 11 lost their graft.

Conclusions: We suggest that histopathological changes of transplant glomerulopathy might be accompanied by inflammation of the microvasculature, such as transplant glomerulitis and peritubular capillaritis, thickening of the peritubular capillary basement membrane, and circulating anti-HLA antibodies. C4d deposition in the PTC is not always present in biopsy specimens of TG. We speculated that C4d deposition in the GC, rather than that in the PTC might be a more characteristic manifestation of TG. Many of the patients with TG had a history of AR. Anti-HLA antibody Class II, particularly when the antibody was DSA Class II, appeared to be associated with the development of TG. The prognosis of grafts exhibiting TG was not too good even under the currently used immunosuppressive protocol.

Keywords: chronic active antibody-mediated rejection; renal transplantation; transplant glomerulopathy.