Distinctive Renal Biopsy Pathology in the Engraftment Syndrome: A Response to Combined Kidney and Bone Marrow Transplantation
AB Farris, D Taheri, L Fazlollahi, AJ Iafrate, RN Smith, AB Collins, N Tolkoff-Rubin, TR Spitzer, T Kawai, AB Cosimi, DH Sachs, RB Colvin. Massachusetts General Hospital (MGH), Boston; MGH, Boston; Emory U, Atlanta; Harvard Medical School, Boston
Background: Renal transplants without maintenance immunosuppression have recently been reported in single-haplotype mismatched living related combined bone marrow (BM)/kidney transplant (tx) recipients, who often develop an idiopathic capillary leak syndrome about 10 days post-tx as donor chimerism becomes detectable, often with spontaneously reversible renal dysfunction. A similar phenomenon seen in both autologous and allogeneic BM txs has been called the “engraftment syndrome (ES).” Here we present novel renal biopsy (bx) findings in this ES.
Design: Indication bxs for graft dysfunction on day 10-12 in an Immune Tolerance Network-sponsored trial (7/9 recipients) were examined by light, immuno- and electron microscopy (EM). Stains included antibodies to Ki67 (MIB-1), CD31, CD68, CD3, and myeloperoxidase. Controls included acute tubular injury (ATI) bxs (n = 5) and normal tx bxs (n = 3) from standard therapy patients at the same time post-tx. Fluorescence in situ hybridization (FISH) was performed in gender mismatched cases for CD45, CD34, and chromosome X and Y.
Results: ES patients had marked ATI, often with interstitial edema, hemorrhage and capillary congestion. Diffuse C4d and focal endothelialitis were each present in 1 case. EM showed glomerular and peritubular capillary (PTC) endothelial injury and loss. CD34 and CD31 stains displayed PTC endothelial cell loss. A marked, significant increase in the number of intracapillary Ki67 cells in glomeruli and PTCs was present compared with ATI bxs. Double staining showed CD31+ and Ki67+ glomerular and PTC endothelial and circulating cells. ATI control cases had mostly tubular cell Ki67 and a similar CD68 cell density. XY FISH showed CD45+ recipient cells in the PTCs with smaller CD34+ proportions.
Conclusions: ES is a spontaneously reversible state with widespread allograft endothelial injury and intracapillary cell proliferation, the latter readily detected with Ki67 and different from ordinary ATI. Whether the mechanism involves a cytokine storm, drug toxicity, and/or allo- or auto-reactivity remains to be defined.
Category: Kidney (does not include tumors)
Monday, March 22, 2010 2:30 PM
Platform Session: Section H, Monday Afternoon