Kidney Week

Abstract: PUB744

Monoclonal IgG4/2-Kappa Deposition Following Eculizumab Therapy for Recurrent Atypical Hemolytic Uremic Syndrome (aHUS) in Kidney Transplantation

Session Information

• Publication Only

Category: Transplantation

• 1702 Transplantation: Clinical and Translational

Authors

• Singh, Priyamvada, Boston University Medical Center, Boston, Massachusetts, United States

Priyamvada Singh,

• Chen, Hui, BMC, Boston, Massachusetts, United States

Hui Chen,

• Gordon, Craig E., None, Natick, Massachusetts, United States

Craig E. Gordon,

• Sloan, John M, Boston MEdical Center, Boston, Massachusetts, United States

John M Sloan,

• Quillen, Karen, Boston University Medical Center, Boston, Massachusetts, United States

Karen Quillen,

• Chitalia, Vipul C., Boston University School of Medicine, Boston, Massachusetts, United States

Vipul C. Chitalia,

• Gautam, Amitabh, Boston Medical Center, Boston, Massachusetts, United States

Amitabh Gautam,

• Henderson, Joel M., Boston University Medical Center, Boston, Massachusetts, United States

Joel M. Henderson,

• Francis, Jean M., Boston University Medical Center, Boston, Massachusetts, United States

Jean M. Francis,

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.