Historically, findings on light and electron microscopy have been used to subclassify membranoproliferative glomerulonephritis (MPGN). Recent advances in understanding of the underlying pathobiology have led to a classification scheme based on immunofluorescence findings. MPGN can result from subendothelial and mesangial deposition of complement owing to dysregulation of the alternative pathway of complement. Complement-mediated MPGN includes dense deposit disease and proliferative glomerulonephritis with C3 deposits. Dysregulation of complement cascade can result from genetic mutations or development of autoantibodies to complement regulating proteins. MPGN is also a pattern of injury that results from subendothelial and mesangial deposition of immune complexes (IC). The common causes of IC-mediated MPGN include chronic infections, autoimmune diseases, and monoclonal gammopathy/dysproteinemias. This category also includes mixed cryoglobulinaemia-glomerulonephritis. Most of these cases are associated with the presence of a hepatitis C virus (HCV) infection. A number of patients with high clinical suspicion for cryoglobulinaemic vasculitis show negative results for the detection of cryoglobulins using standard methods, but are found to have detectable levels of cyoprecipitable immunoglobulins (hypocryoglobulins) using more sensitive techniques. A subset of patients with low level of circulating hypocryoglobulins can present with glomerulonephritis, often isolated, with membranoproliferative pattern MPGN. They can be negative for HCV infection detection and can have normal rheumatoid activity and complement levels. Hypocryoglobulinemic nephritis might represent a distinct entity.
Keywords: Membranoproliferative Glomerulonephritis, C3 Glomerulonephritis, Hypocryoglobulinemic Nephritis