MO085MONOCLONAL GAMMOPATHY OF UNKNOWN SIGNIFICANCE AMONG MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS PATIENTS

Abstract

Abstract Background and Aims Monoclonal gammopathy is an entity where a B-cell or plasma cell clone produces monoclonal immunoglobulin. When paraproteinemia and a kidney disease is discovered without criteria for treatment of haematological malignangy, the entity is called monoclonal gammopathy of unknown significance (MGUS) or of renal significance (MGRS). It can cause variable histology, among which membranoproliferative glomerulonephritis (MPGN) has been described. Direct entrapment of paraprotein in glomeruli/tubules can be observed by immunofluorescence (IF), but IF can also be negative as paraprotein can cause complement-associated disease by acting as an activator of the classical pathway or as a dysregulator of the alternative pathway. Electron microscopy (EM) is needed to differentiate possible organized deposits. Method We investigated the prevalence, clinical parameters, histology, and the type of monoclonal gammopathy in biopsy-proven MPGN between 2006-2017. A total of 15 adult patients with a detected urine and/or serum paraprotein with concurrent biopsy-proven diagnosis were discovered among 60 patients (Figure 1). Two diagnostic biopsies were from transplants. Results MGUS was diagnosed in 15/60 (25%) of patients. Clinical variables are summarized in Table 1. The mean age at presentation was 59 years (37-79), 47-% were males. Smoldering myeloma was diagnosed in 2 (13%) patients and overt malignancy in 3 (20%) patients. Histological features are summarized in Table 2. There were 7 (47%) with dominant staining for C3 (6 with C3 glomerulonephritis, 1 Dense Deposition Disease) and 8 (53%) with dominant staining for Ig, of which 4 (31%) had mesangioproliferative, 4 (31%) membranoproliferative, 3 (23%) minimal change, 2 (15%) crescentic and 1 (8%) exudative pattern in light microscopy (LM). Seven (47%) biopsies, which did not stain for kappa or lambda light chains. The most common EM deposit location was subendothelial (69%). Conclusion MPGN was associated with a significant risk of underlying monoclonal gammopathy, as many (25%) patients were diagnosed with concurrent MGUS. When MPGN is observed, it should prompt investigations of the possible underlying monoclonal gammopathy and possibly, hematological neoplasm.