Abstract: PUB744
Monoclonal IgG4/2-Kappa Deposition Following Eculizumab Therapy for Recurrent Atypical Hemolytic Uremic Syndrome (aHUS) in Kidney Transplantation
Session Information
Category: Transplantation
- 1702 Transplantation: Clinical and Translational
Authors
- Singh, Priyamvada, Boston University Medical Center, Boston, Massachusetts, United States
- Chen, Hui, BMC, Boston, Massachusetts, United States
- Gordon, Craig E., None, Natick, Massachusetts, United States
- Sloan, John M, Boston MEdical Center, Boston, Massachusetts, United States
- Quillen, Karen, Boston University Medical Center, Boston, Massachusetts, United States
- Chitalia, Vipul C., Boston University School of Medicine, Boston, Massachusetts, United States
- Gautam, Amitabh, Boston Medical Center, Boston, Massachusetts, United States
- Henderson, Joel M., Boston University Medical Center, Boston, Massachusetts, United States
- Francis, Jean M., Boston University Medical Center, Boston, Massachusetts, United States
Background
Eculizumab is emerging as a promising therapy for aHUS. We present a patient with rapid resolution of recurrent aHUS after kidney transplantation following eculizumab therapy but with evidence of monoclonal IgG4/2-kappa deposition on repeat kidney biopsy
Methods
A 22-year-old male with CKD stage 5 of unknown etiology underwent preemptive living related kidney transplantation from his sister. His post-operative course was complicated by thrombocytopenia on day 3 after transplant (nadir platelet count: 36k/ul) and delayed graft function. Testing revealed elevated LDH (673 U/L, normal 171-308), low haptoglobin (<7 mg/dL, normal 44-184), and schistocytosis on peripheral blood smear. Eculizumab was initiated for possible recurrent aHUS on day 3 post-transplant. Kidney biopsy performed on day 5 post-transplant following a recovery of thrombocytopenia confirmed the diagnosis of acute thrombotic microangiopathy (TMA). Hematological parameters improved rapidly following treatment but the renal function did not improve as expected. A repeat kidney biopsy performed after 5 doses of eculizumab demonstrated complete resolution of TMA features on a background of essentially normal renal parenchyma. Interestingly, immunofluorescence microscopy revealed monoclonal staining for IgG4/2-kappa in glomeruli, vasculature, and focally in tubular basement membranes. The deposits suggest eculizumab deposition because eculizumab is a hybrid monoclonal immunoglobulin comprised of IgG4/2-kappa chains. IgG4/2-kappa deposits are rare pathological findings seen following eculizumab therapy.
Conclusion
Early identification and treatment of recurrent TMA after transplantation require a high clinical suspicion but result in improved graft function and patient outcome. IgG4/2-kappa deposits are a rare pathological finding following effective eculizumab therapy but the long-term effects of these deposits on renal function remain unknown.