Atypical Hemolytic Uremic Syndrome Secondary to Lupus Nephritis, Responsive to Eculizumab

Abstract

Among the spectrum of disease manifestations associated with systemic lupus erythematosus, lupus nephritis is particularly concerning due to the potential for renal failure. This autoimmune attack may not, however, be limited to the kidney and is increasingly being recognized as a trigger for atypical Hemolytic Uremic Syndrome (aHUS). Atypical HUS falls under the spectrum of the thrombotic microangiopathies (TMAs) - a group of disorders characterized by microangiopathic hemolytic anemia, thrombocytopenia, and end organ damage. Although plasma exchange is considered first-line therapy for thrombotic thrombocytopenic purpura - a TMA classically associated with autoimmune depletion of ADAMTS-13 - aHUS demonstrates less reliable responsiveness to this modality. Instead, use of the late complement inhibitor Eculizumab has emerged as an effective modality for the management of such patients. Diagnosis of aHUS, however, is largely clinically based, relying heavily upon a multidisciplinary approach. Herein we present the case of a patient with atypical HUS successfully treated with Eculizumab in the setting of Class IV-G (A) lupus nephritis and hypocomplementemia.

Keywords: Atypical hemolytic uremic syndrome; Lupus nephritis; Microangiopathic hemolytic anemia; Thrombotic microangiopathy.

Figure 1.

Renal biopsy images demonstrating the presence of Class IV G (active) lupus nephritis. A) Jones Silver stain demonstrating fibrin thrombus (arrow) within a hilar arteriole; B) Hematoxylin & Eosin stain demonstrating diffuse endocapillary hypercellularity (white arrows) and wire loops (black arrow).

Figure 2.

Therapeutic course. Horizontal lavender boxes depict steroids [and hydroxychloroquine (HQ) course; PO = Prednisone dose; MP = Methylprednisolone, 1 gram]. M = Mycophenolate Mofetil; R = Rituximab (1000 mg IV); C = Cyclophosphamide (C1 500 mg IV; C2 800 mg IV); E = Eculizumab; PE = Therapeutic Plasma Exchange; QD = daily; IV = Intravenous. Note that platelet counts were responsive to TPE but hemolysis-engendering-transfusion (downward pointing arrows, each one representing a unit of RBCs) continued in the face of continued plasma exchange. Eculizumab was dosed on days 49 (900 mg IV shown), 56 (900 mg IV shown), and 63 (900 mg IV, not shown), 70 (900 mg IV, not shown), and 77 (1200 mg IV, not shown) leading up to day 83 repeat laboratory testing. Eculizumab (1200 mg IV every 14 days) has been continued thereafter. Detectability of haptoglobin (and hence, cessation of hemolysis) was not established until after 5 doses of eculizumab, at which time the creatinine had finally normalized.