Emerging Issue of Monoclonal Gammopathy of Renal Significance with Nonorganized Deposits on Electron Microscopy

Background: Monoclonal Gammopathy of Renal Significance (MGRS) is a group of disorders where a B-cell or plasma cell clone produce a nephrotoxic monoclonal immunoglobulin that causes kidney damage. Response to conventional immunosuppressive therapies is poor, while evidence in the literature supports clone-mediated therapy. This study aims to raise awareness of the importance of renal biopsies in correctly identifying patients with MGRS, and to evaluate the response to clone-directed therapy in patients with MGRS and non-organized deposits. Methods: We retrospectively collected patients (pts) diagnosed with MGRS at our center from 2017 to 2024, evaluating treatment protocols used: CyBorD (cyclophosphamide, bortezomib and dexamethasone), daratumumab, rituximab. Results: We identified 68 pts with MGRS: 25 had AL amyloidosis, 15 cryoglobulinemic glomerulonephritis, 9 proliferative glomerulonephritis with monoclonal immunoglobulin deposits, 5 monoclonal immunoglobulin deposition disease, 2 immunotactoid glomerulonephritis, 3 monoclonal fibrillary glomerulonephritis, 3 monotypic membranous nephropathy, 1 cryofibrinogen glomerulonephritis, 1 light chain proximal tubulopathy and 1 thrombotic microangiopathy. Seventeen pts had MGRS with non-organized deposits. Nine pts received clone-based therapy and had at least 6 months of follow-up; 8 of them reached at least 12 months of follow-up. Seven out of eight pts (87.5%) achieved a complete renal response at 12 months, 1 patient remained non-responder. Four pts maintained complete renal response at the last follow-up, 2 relapsed (currently on second-line treatment) and one is under investigation for increasing proteinuria levels. All pts were End Stage Renal Disease-free at last follow-up. Five out of nine pts underwent repeated renal biopsy during follow-up period. Conclusion: MGRS may be a progressive disease that, if untreated, can lead to end stage renal failure and recur after renal transplantation. Although there are no randomized controlled trials to guide the optimal approach to therapy, clone-directed therapy has shown good results in literature and also in our cohort.