Idiopathic Cryoglobulinemic Membranoproliferative Glomerulonephritis Treated with Rituximab

Introduction: Mixed cryoglobulinemia without an identifiable cause is termed essential or idiopathic cryoglobulinemia. While most cases are associated with hepatitis C or lymphoproliferative disorders, idiopathic cases account for 10%. Optimal management remains unclear in this subgroup. We present a case of idiopathic cryoglobulinemia resulting in membranoproliferative disease successfully treated with rituximab. Case Description: A 68-year-old male with well controlled diabetes mellitus, hypertension presented with shortness of breath and facial swelling. Initial labs showed a serum creatinine of 4.7 mg/dl and albumin of 2.6 g/dl, with a baseline creatinine of 1.1 mg/dL 2 years prior. Urine sediment showed white cell casts and non-dysmorphic RBCs. Urine protein-creatinine was >10g/g with urine albumin-creatinine being > 3.8 g/g. Serological workup including ANA, Sjogren's, HIV, hepatitis B/C, RPR, serum cryoglobulins were negative. C3 and C4 were normal. Kidney biopsy revealed membranoproliferative glomerulonephritis with immune complex deposits in short tubular forms suggesting cryoglobulins. IF was positive for IgG, IgM, kappa, lambda and C3. He was treated with prednisone taper and two doses of rituximab, which resulted in a reduction in serum creatinine from 2.5 to 1.43 and proteinuria from 2g/g to 200mg/g in one month. Discussion: Detection of cryoglobulins requires the sample to be kept at 37°C until centrifugation. While low C4, CH50 and positive RF serologies are often seen with cryoglobulinemia, normal C4 does not exclude the diagnosis. Treatment of mixed cryoglobulinemia includes immunosuppression and treatment of underlying causes. In idiopathic cases corticosteroids and rituximab are often used. Our patient showed a marked clinical response to this regimen. Previously described regimens are steroids, rituximab, cyclophosphamide, alpha interferon and in case of type 1 cryoglobulinemia, apheresis is offered for hyper viscosity syndromes.