Pathology, Serology and Clinical Characteristics of 68 Patients with Chronic Humoral Renal Allograft Rejection (CHR)
AB Farris, J Gaut, W Wong, P Della Pelle, N Brousaides, AB Collins, S Saidman, EE Schneeberger, RN Smith, RB Colvin. Massachusetts General Hospital, Boston, MA
Background: CHR is a newly recognized category in the Banff classification system. We sought to define the spectrum of pathology, clinical features and pathogenetic insights by analysis of a large cohort of patients from one center.
Design: All renal transplant biopsies diagnosed with CHR based on Banff'05 criteria were identified in pathology and clinical databases (7/1993-7/2008). The pathology of the first C4d+ biopsies showing CHR were correlated with serology and clinical features.
Results: CHR was diagnosed in 68 recipients (48 males, 20 females; 7.8% of 997 biopsies), 7.75.2 yrs post-transplant (0.6-22), with a mean Cr of 4.62.8 mg/dl (1.3-11.9) and proteinuria >1 gm/24 hr (0.03-9.5) in 50%. All had C4d in peritubular capillaries (PTC), but 18% were focal. Five variants were recognized by combinations of transplant glomerulopathy (TG), transplant arteriopathy (TA) or interstitial fibrosis (IF). The commonest variant was TG+TA+IF (44%) followed by TG+IF (25%). However, TG negative forms were identified in 25% and an IF alone variant in 13%. CHR occurred together with acute humoral or cellular rejection in 15% and 16%, respectively. Donor specific antibodies (DSAs) were present in 89%; class II DSAs were associated with TG+ variants (P<0.0005). PTC multilamination present in 35/56 (64%) by EM did not correlate with TG+. Glomerular and PTC mononuclear inflammation included CD68+, CD16+ (FcgR+) and Tbet+ cells with infrequent T cells. Prognosis was poor with 1 and 5 year graft survival 54% and 8%, respectively.
|Variant||TG||IF||TA||C4d>50%||DSA+||DSA Specificity (%)|
|N(%) of CHR||% I Only||% II Only|
Conclusions: CHR is common with heterogeneous pathology and combinations of TG, TA, IF and PTC multilamination, sometimes with superimposed acute humoral or cellular rejection. TG is strongly correlated with class II DSA. The usual criterion of >50% C4d deposition is insensitive for CHR (vs AHR). FcgR+ cells are abundant in capillaries and may be part of the pathogenesis. Diagnosis of CHR, which carries a poor prognosis, depends on recognition of the diverse pathologic manifestations.
Category: Kidney (does not include tumors)
Tuesday, March 10, 2009 1:00 PM
Poster Session IV # 187, Tuesday Afternoon