Thrombotic Microangiopathy and Peritubular Capillary C4d Expression in Renal Allograft Biopsies

Background and objectives This study characterizes the pathologic and clinical relationships of thrombotic microangiopathy (TMA) to antibody-mediated rejection (AMR) in renal allograft biopsies. Design, setting, participants, & measurements Consecutive renal allograft biopsies, routinely stained for C4d over a period of 51 months (n = 1101), were reviewed. For comparative analysis of histology and clinical features, additional patients with TMA and peritubular capillary (PTC) C4d (n = 5) were combined with those identified in the 51-month period of review (n = 6). Results One hundred eighty-two of 1073 adequate biopsies from 563 allografts had PTC C4d in the study period. Six of 37 biopsies with TMA had PTC C4d (five at <= 90 days and one at 213 days). Early (<= 90 days) C4d+ biopsies (n = 5) had more frequent TMA (11.9% C4d+ versus 3.4% C4d-; odds ratio, 3.84; P = 0.03). Graft loss was significantly greater in an early C4d+TMA+ group (n = 5 study + 2 archival patients) than in C4d+ controls without TMA (n = 21) (57% versus 9.5%; P = 0.02). Early TMA+C4d+ biopsies had more severe glomerulopathy and less severe arteriolopathy than TMA+C4d- and had more frequent neutrophilic capillaritis than TMA-C4d+ biopsies. Conclusions TMA was infrequent in this series of unselected, consecutive, renal allograft biopsies (3.4%). PTC C4d may be a significant risk factor for early TMA, and TMA is associated with glomerular thrombi and neutrophilic capillaritis. TMA in allografts with suspected AMR may portend a higher risk of graft loss. Clin J Am Soc Nephrol 6: 395-403, 2011. doi: 10.2215/CJN.05870710