Monoclonal gammopathy of renal significance (MGRS) is defined as a B-cell or plasma cell clonal lymphoproliferation that produces a monoclonal immunoglobulin causing kidney lesions without leading to tumor-related complications. Although MGRS does not require hematological therapy based on tumor burden, most therapies are still carried out in accordance with hematological guidelines. AL amyloidosis is the most common form of MGRS, and substantial evidence has been accumulated regarding its treatment and response assessment. However, evidence for non-AL amyloidosis MGRS remains limited because of its rarity. This report describes six cases of non-AL amyloidosis MGRS, with the aim of contributing to the evidence base for this rare disease entity by outlining their clinical courses. The six cases of non-AL amyloidosis MGRS included two with cryoglobulinemic glomerulonephritis and one each with C3 glomerulopathy, histiocytic glomerulopathy, light chain deposition disease (LCDD), and heavy chain deposition disease (HCDD). In an untreated case, one patient with C3 glomerulopathy progressed to end-stage kidney disease within 30 months of diagnosis. In contrast, patients with cryoglobulinemic glomerulonephritis, LCDD, and HCDD who received clone-directed therapy and achieved hematological complete response exhibited renal response. Of those who underwent clone-directed therapy but achieved only a hematological very good partial response, one case of cryoglobulinemic glomerulonephritis showed renal response, whereas another case of histiocytic glomerulopathy did not. In all six cases, fluctuations in the difference between involved and uninvolved free light chains (dFLC) paralleled changes in urinary protein levels, suggesting that dFLC may serve as a useful marker of disease activity. Although two of the three patients who did not achieve sufficiently reduced dFLC levels failed to obtain a renal response, all three patients who achieved greater reductions in dFLC demonstrated favorable kidney outcomes. These cases underscore the importance of implementing clone-directed therapy in the management of non-AL amyloidosis MGRS and suggest that achieving lower dFLC levels may contribute to improved kidney outcomes. Not applicable
Nobayashi et al. (2026) studied this question.