Transplant Glomerulopathy, Pathogenesis and Evolution
Nicole Nelles, Smaroula Dilioglou, Marjan Afrouzian, Lillian Gaber, Roberto Barrios, Luan Truong. Methodist Hospital, Houston, TX; University of Texas Medical Branch, Galveston, TX
Background: Transplant glomerulopathy (TG) is a frequent finding in renal allografts. TG often leads to progressive graft dysfunction and loss. The pathogenesis and evolution of TG, while not well defined, appears to be complex involving alloimmune and non-immune mechanisms that may act separately or overlap. How much antibody-mediated mechanisms, as evidenced by C4d in tissue and/or circulating donor specific antibodies (DSAs), participate in its development remains unsettled.
Design: Renal Tx biopsies with TG in 2010 and 2011 were reviewed. The collected data included morphologic changes of TG including C4d tissue deposition, concurrent lesions including rejection and chronic injury, and type and levels of donor-specific anti-HLA class I and II antibodies. The preceding diagnostic and follow-up biopsies were subjected to a similar review.
Results: Out of a total 845 transplant biopsies in 603 recipients during the study period, TG was first noted in 41 index biopsies (4.9%) in 41 patients. Among these 41 biopsies, 31 displayed glomerular capillary C4d staining, and the staining was global diffuse in all of them (Group 1). Glomerular C4d was not seen in the remaining 10 biopsies (Group II). Comparison of Group I and II was made for C4d in peritubular capillaries (55% vs 50%); antibody-mediated rejection (39% vs 3%); cell-mediated rejection (16% vs 0.17%). DSA data at time of biopsies were available in 7 patients, with 5/5 (100%) positive for Group I and 1/2 (50%) for Group II. Within Group I, there were 17 preceding biopsies with, 9 (53%) showing C4d positive glomeruli and 14 follow-up biopsies with 12 (86%) showing C4d positive glomeruli. Within Group II, there were 8 preceding biopsies, with 4 (50%) showing C4d positive glomeruli, and 6 follow-up biopsies with all 6 (100%) showing C4d positive glomeruli.
Conclusions: TG was found in 4.9% of renal allograft biopsies in a single institution. Although absence of glomerular C4d is noted in a significant portion of TG, virtually all cases of TG are related to DSA during its course, confirming an exclusive pathogenetic role of DSA. A differential pathogenesis for DSA is possible, since a significant portion of TG occurs as an isolated finding without associated cell- or antibody-mediated rejection and C4d is absent in peritubular capillaries in up to a half of the C4d + TG. Glomerular C4d may serve as a sensitive surrogate marker for the development of TG, long before morphologic changes.
Category: Kidney (does not include tumors)
Monday, March 4, 2013 1:00 PM
Poster Session II # 220, Monday Afternoon