P0628 - A Case of Proliferative and Membranous Lupus Nephritis Complicated by Cryoglobulin-like Hyaline Thrombi

Introduction: Renal disease is a devastating complication of systemic lupus erythematosus (SLE). In addition to glomerular involvement, vascular disease is not uncommon. We present a case of lupus nephritis (LN) in the setting of thrombotic microangiopathy (TMA) with a rare instance of cryoglobulin-like thrombi.

Case: a 21-year-old woman with past medical history of SLE complicated by Class VI nephritis was admitted with worsening kidney function which showed a serum creatinine of 2.9 mg/dL from a baseline of <1.5. She reported shortness of breath, cough, and a headache. She endorsed compliance with all of her medications and did not notice any urine output changes. Blood pressure was 200/123. On exam malar rash, Cushingoid appearance, and hair loss was noted. Initially, serum creatinine trended to > 6, but over the next few days, downtrended. Renal biopsy was significant for evidence of class IV and V, diffuse proliferative and membranous lupus nephritis with glomerular capillary loop thrombi. Ultrastructurally, the thormbi appeared similar to those seen in cryoglobulinemia. However, serum cryoglobulins and hepatitis B and C viral panels were negative. Patient received one dose of cyclophosphamide and discharged on high dose steroids and hydroxychloroquine. Unfortunately, the patient’s renal function declined and is she is currently on hemodialysis.

Discussion: Lupus nephritis is primarily caused by anti-dsDNA immune complex deposition in the glomerular basement membrane and mesangium, leading to activation of the complement cascade, but is often multifactorial. Vascular involvement in LN is most often associated with immune complex deposition, TMA, vasculitis, atheroembolic disease or antiphospholipid antibodies. The majority of acute TMA cases are the result of fibrin thrombi, and there is scant literature documenting cryoglobulinemic thrombi. Cryoglobulin clot formation has primarily been documented in case reports with cryoglobulinemia associated with HCV or HBV infection. Mixed cryoglobulinemia may be complicated by glomerulonephritis and TMA, but only 6.4% of the time is it associated with rheumatologic disease. While rare, cryoglobulin clots may be present even with a negative serum cryoglobulin. Cryoglobulin deposition beneath renal vascular endothelium causes complement cascade activation, and a hypercoaguable state with fibrin clots, but rarely cryoglobulin clots. All patients with class IV and V LN are treated with aggressive antihypertensive, antiproteinuric, and statin-based, and induction immunosuppressive therapies with cyclophosphamide, followed up by 1-2 years of maintenance therapy with mycophenolate-mofetil or azathioprine. Patients with confirmed essential mixed cryoglobulinemia may consider rituximab instead of cyclophophamide, but our patient was treated according to standard Class IV recommendations.

Conclusion: This patient documents a rare case of acute lupus nephritis complicated by renal vascular involvement with cryoglobulin-like thrombi. It is important to keep a broad differential