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PGNMID Clone-Directed Therapy — ESENeph MCQ

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HardGlomerulonephritisPGNMID Clone-Directed TherapyESENeph

A 45-year-old man with biopsy-proven proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID) has proteinuria of 4 g/day and eGFR 50. Serum free light chains show mild kappa excess. Bone marrow shows 3% clonal plasma cells. What is the treatment approach?

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Correct answer: D — Clone-directed therapy (e.g. Bortezomib-based regimen) targeting the underlying B-cell or plasma cell clone, even though haematological criteria for myeloma are not met

PGNMID is a form of MGRS where a small B-cell or plasma cell clone produces monoclonal immunoglobulin that deposits in glomeruli causing proliferative GN. Despite not meeting myeloma criteria, the clone must be treated to prevent ongoing renal damage. Clone-directed therapy (Bortezomib-based for plasma cell clones; Rituximab-based for B-cell clones) is recommended by the International Kidney and Monoclonal Gammopathy Research Group (IKMG). Haematological response (normalisation of free light chains) correlates with renal response.

Reference: Leung et al 2019 – MGRS; IKMG 2017 – MGRS Treatment Recommendations