A clone-directed approach may improve diagnosis and treatment of proliferative glomerulonephritis with monoclonal immunoglobulin deposits

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

“…Two similar cases with complete renal response while the M-protein was still detectable after clone-directed therapy were described in a recent case series [6], indicating that renal response is not contingent on the resolution of the M-protein in PGNMID. The fact that the M-protein increased to the pretreatment level without any signs of recurrent glomerulonephritis suggests that a factor besides Table 1 Summarized characteristics of the presented cases and 65 cases from previously published case series of PGNMID Summary of case characteristics from Nasr et al [4] (complete response defined as remission of proteinuria to < 500 mg/day with normal renal function and partial response as reduction in proteinuria by at least 50% and to < 2 g/day with stable renal function), Gumber et al [6] (complete response defined as stabilization or improvement in eGFR and urine proteinuria improvement to < 0.5 g/g on urine protein-to-creatinine ratio or < 0.5 g/24-h urine collection and partial response as stabilization or improvement of eGFR, but not to normal, and > 50% decrease in proteinuria) and Kousios et al the M-protein presence or quantity is involved in the development of PGNMID. Possibly, specific characteristics of the M-protein and its interaction with the patient's immune system play a role.…”

“…However, in contrast to other forms of MGRS, the detection rate of serum M-protein in PGNMID is only 32-37% and a pathologic clone is found in a bone marrow biopsy in only 25-42% of cases [6][7][8]. Nonetheless, empirical treatment prescribed to target a hypothesized underlying clone is associated with renal response in cases without a detectable clone [6].…”

“…g Biopsy after 3 years: Immunofluorescence still showed mesangial deposits of IgM and C3c ◂ pattern in the glomeruli restricted to a single immunoglobulin heavy chain (mostly IgG) and light chain subtype, and non-organized mesangial and subendothelial deposits can be seen in electron microscopy. While there is limited evidence, there is consensus that treatment of MGRS should target the underlying clone, since complete hematological response is associated with the best renal outcomes [1,6]. However, in contrast to other forms of MGRS, the detection rate of serum M-protein in PGNMID is only 32-37% and a pathologic clone is found in a bone marrow biopsy in only 25-42% of cases [6][7][8].…”

“…While there is limited evidence, there is consensus that treatment of MGRS should target the underlying clone, since complete hematological response is associated with the best renal outcomes [1,6]. However, in contrast to other forms of MGRS, the detection rate of serum M-protein in PGNMID is only 32-37% and a pathologic clone is found in a bone marrow biopsy in only 25-42% of cases [6][7][8]. Nonetheless, empirical treatment prescribed to target a hypothesized underlying clone is associated with renal response in cases without a detectable clone [6].…”

“…The question remains whether the M-protein disappeared spontaneously or that the prednisolone or azathioprine attenuated the PGNMID in an early stage. Renal response on immunosuppressive therapy has been described in various cases of MGRS, but small retrospective studies suggest that clone-directed regimens result in higher renal response rates [6,12,13].…”