Clone-directed therapy for proliferative glomerulonephritis with monoclonal immunoglobulin depositions: is it always necessary?

Monoclonal gammopathy of renal significance (MGRS) encompasses a group of disorders in which a monoclonal immunoglobulin (M-protein) secreted by a B-cell or plasma cell clone causes renal disease. Proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) is a form of MGRS where M-protein is deposited in the glomerulus. Although evidence is limited, the current consensus is that therapy for PGNMID should be directed against the underlying clone. However, it is conceivable that there is heterogeneity in the renal prognosis of PGNMID and that not all patients have need for clone-directed therapy. Here, we report two cases of PGNMID with IgM-kappa gammopathy. In one case of a 53-year-old woman the glomerulonephritis resolved without clone-directed therapy. In the other case of a 34-year-old woman clone-directed therapy was discontinued due to adverse effects. Although no hematological response was achieved, the PGNMID resolved. In both cases there are no signs of a recurrent glomerulonephritis in over 3 years of follow-up. Here, we review the literature and suggest that some PGNMID patients have a favorable renal prognosis in whom clone-directed therapy can be withheld or postponed. Further research is warranted to yield predictors to identify these patients and to better understand the disease course of PGNMID.