Proliferative Glomerulonephritis With Fibrils, Monoclonal κ Light Chain, and C3 Deposits

There is increasing recognition of monoclonal gammopathy as a cause of proliferative glomerulonephritis (GN), including cases in which glomerular deposition of monoclonal immunoglobulin (mIg) is demonstrated. Recently, proliferative GN with mIg deposits (PGNMID) has incorporated a light chain (LC) variant of the disease (termed PGNMID-LC). Intriguingly, glomerular co-deposition of complement C3 is found in addition to monotypic LC, implying complement activation via the alternative pathway (AP). We present a unique case of proliferative GN in a 42-year old man who presented with nephrotic syndrome and was found to have κ-LC multiple myeloma. Immune staining of the glomerulus was positive only for κ-LC and C3, with the striking appearance of non-amyloid fibrils on electron microscopy. Following clonally targeted therapy for myeloma, the renal clinical abnormalities resolved completely. We present detailed molecular studies for LC and complement and consider local mechanisms whereby monoclonal κ-LC fibrils may have triggered AP activation within the glomerulus.