Monoclonal gammopathy of renal significance: when MGUS is no longer undetermined or insignificant

Abstract

Multiple myeloma is the most frequent monoclonal gammopathy to involve the kidney; however, a growing number of kidney diseases associated with other monoclonal gammopathies are being recognized. Although many histopathologic patterns exist, they are all distinguished by the monoclonal immunoglobulin (or component) deposits. The hematologic disorder in these patients is more consistent with monoclonal gammopathy of undetermined significance (MGUS) than with multiple myeloma. Unfortunately, due to the limitations of the current diagnostic schema, they are frequently diagnosed as MGUS. Because treatment is not recommended for MGUS, appropriate therapy is commonly withheld. In addition to endstage renal disease, the persistence of the monoclonal gammopathy is associated with high rates of recurrence after kidney transplantation. Preservation and restoration of kidney function are possible with successful treatment targeting the responsible clone. Achievement of hematologic complete response has been shown to prevent recurrence after kidney transplantation. There is a need for a term that properly conveys the pathologic nature of these diseases. We think the term monoclonal gammopathy of renal significance is most helpful to indicate a causal relationship between the monoclonal gammopathy and the renal damage and because the significance of the monoclonal gammopathy is no longer undetermined. (Blood. 2012;120(22):4292-4295)

Rituximab–cyclophosphamide‐dexamethasone is highly effective in patients with monoclonal Ig deposit‐related glomerulopathy and indolent non‐Hodgkin lymphomas

“…In patients with MGUS-related renal disease, a recent workshop suggested replacing this term with "monoclonal gammopathy of renal significance" and requested a dedicated treatment to obtain a complete immunological response [6]. Less commonly, iNHLs may also promote glomerulonephritis associated with monoclonal deposits [3,12,13], with extremely heterogeneous pathologic pattern as exemplified in our series.…”

“…Among the 12 patients who received RCD as a first-line therapy, eight (67%) obtained a complete renal response. Among the nine patients with a complete haematological response, six (67%) reached a complete renal response (median time between haematological and renal complete response was 3 months [1][2][3][4][5][6][7][8][9][10]), compared with two that did not reach a complete haematological response (not significant). A significant reduction in 24-hr proteinuria was observed over time following RCD therapy as shown in Fig.…”

“…To date, most published series on glomerulopathy with monoclonal Ig deposits have been based on pathologic patterns [3,6,[12][13][14][15]. Because of the wide heterogeneity of treatments in these series (e.g., no treatment, steroids only, rituximab, or combined chemotherapy), no firm recommendations for iNHL treatment are available.…”

“…In particular, in patients with iNHL and low tumor burden, who usually do not require immunochemotherapy per se, the choice of either single or combination of drug(s) to target the malignant clone and renal inflammation (steroids, alkylating agents, the B-cell depleting monoclonal antibody rituximab, or the proteasome inhibitor bortezomib) remains elusive. Recently, the International Kidney and Monoclonal Gammopathy Research Group proposed renal-pattern and malignancy-based recommendations to uniformly manage monoclonal gammopathy of renal significance (MGRS, [6]). In 2013, this group further delineated the concept of MGRS and proposed some therapeutic options that require validation in large retrospective or prospective studies [7].…”

A Patient with Abnormal Kidney Function and a Monoclonal Light Chain in the Urine

“…This is made even more difficult since renal impairment unrelated to cast nephropathy is not considered a myeloma-defining event, because these conditions do not require the tumor burden seen in MM. To capture these as clinically significant hematologic conditions, the term monoclonal gammopathy of renal significance (MGRS) was introduced (15). Although hematologically, MGRS behaves more similar to MGUS and SMM, it differentiates itself by its nephrotoxicity.…”