How I treat monoclonal gammopathy of renal significance (MGRS)

Abstract

Recently, the term monoclonal gammopathy of renal significance (MGRS) was introduced to distinguish monoclonal gammopathies that result in the development of kidney disease from those that are benign. By definition, patients with MGRS have B-cell clones that do not meet the definition of multiple myeloma or lymphoma. Nevertheless, these clones produce monoclonal proteins that are capable of injuring the kidney resulting in permanent damage. Except for immunoglobulin light chain amyloidosis with heart involvement in which death can be rapid, treatment of MGRS is often indicated more to preserve kidney function and prevent recurrence after kidney transplantation rather than the prolongation of life. Clinical trials are rare for MGRS-related kidney diseases, except in immunoglobulin light chain amyloidosis. Treatment recommendations are therefore based on the clinical data obtained from treatment of the clonal disorder in its malignant state. The establishment of these treatment recommendations is important until data can be obtained by clinical trials of MGRS-related kidney diseases.

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

“…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.…”

“…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].…”

Biochemical markers in early diagnosis and management of systemic amyloidoses

“…Repeated measurements of microalbuminuria and eGFR, in individuals at risk (see above), could help identify those who are developing renal amyloid deposits in early phases [7,8,10,39]. This is of paramount importance, since recent evidence gathered on a large patient population of 461 patients shows that early diagnosis, when proteinuria is < 5 g/24 h and eGFR > 60 mL/min, allows intervention when renal damage is still reversible.…”

“…Patients who obtain good quality response to treatment are protected from loss of renal function [40]. In AL amyloidosis, approximately 70% of patients present with proteinuria and two thirds are in the nephrotic range, whereas elevated creatinine is noted in one half of the patients [39,41]. Serum cystatin C has also been evaluated as an early indicator of impaired GFR in patients with amyloidosis, in particular AA type [42,43].…”

Laboratory testing in monoclonal gammopathy of renal significance (MGRS)

“…As the hematologic characteristics behave more like MGUS in many of these patients, treatment with cytotoxic agents had been traditionally withheld. Differentiating MGRS from the MGUS opened the door to treating these low tumor burden conditions with cytotoxic agents without the need for a diagnosis of MM [15]. The differences in hematologic characteristics do require a slightly different approach to treatment of MGRS as compared with MM or malignant lymphoma.…”