Monoclonal Gammopathy of Renal Significance: Clinical and Histological Efficacy of a Bortezomib-Based Regimen

Abstract

Monoclonal Gammopathy of Renal Significance (MGRS) is a group of heterogeneous disorders characterized by renal dysfunction secondary to the production of a monoclonal immunoglobulin by a nonmalignant B cell or plasma cell clone. We report the clinical and histological outcomes of two patients with biopsy-proven MGRS: one patient showed membranoproliferative glomerulonephritis with monoclonal k-light chain and C3 deposits, the second patient showed immunotactoid glomerulopathy. Both patients were treated with a 9-month chemotherapy protocol including bortezomib, cyclophosphamide, and dexamethasone. Renal biospy was repeated after 1 year. The estimated glomerular filtration rate (eGFR) increased from 22.5 (baseline) to 40 ml/min per 1.73 m2 after 12 months, then to 51.5 ml/min per 1.73 m2 after 24 months; proteinuria decreased from 4.85 (baseline) to 0.17 g/day after 12 months, then to 0.14 g/day after 24 months. Repeat renal biopsies showed a dramatic improvement of the glomerular proliferative lesions and near complete disappearance of the immune deposits. A bortezomib-based treatment proved very effective and was well-tolerated in the two patients presenting with clinically and histologically aggressive MGRS.

Polyclonal Immunotactoid Glomerulopathy Associated with Monoclonal Gammopathy of IgM Type and Underlying Plasmacellular Disease: Successful Treatment with Rituximab Alone

“…In our case, cryoglobulinemia is unlikely because of lack of light chain restriction in the kidney biopsy despite monoclonal gammopathy and the lack of systemic signs of cryoglobulinemia. The clinical presentation of ITG typically involves hypertension, proteinuria, hematuria, and renal insufficiency [ 17 ]. As stated above, ITG commonly goes along with hematologic disorders or MGUS and might even occur years before a hematologic diagnosis can be made [ 18 , 19 ].…”

Recurrent glomerulonephritis after kidney transplantation: a practical approach

“…In recipients with recurrent C3GN or DDD, anticomplement therapy with eculizumab may be considered, although the timing, dose, duration and efficacy of anticomplement therapy combined with the concurrent use of plasmapheresis, cyclophosphamide and anti-B cell therapy remain poorly defined [92–99]. In recipients with immune complex-mediated GN, treatment of the underlying plasma cell dyscrasias (if present) or monoclonal gammopathies of renal significance should be undertaken, although the efficacy of B and plasma cell clone-directed therapy for the latter disease remains unclear [36 ▪▪ ,100 ▪ ,101] (Table 2 and Fig. 1).…”