Kidney Week 2025 Early Program - Glomerular Diseases: 2025 Update-Understanding and Managing Monoclonal Gammopathy of Renal Significance Spectrum Diseases

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Video Summary

Dr. Nelson Lin reviews monoclonal gammopathy of renal significance (MGRS), created to address patients with kidney lesions caused by a monoclonal gammopathy who do not meet multiple myeloma criteria and therefore were historically observed rather than treated. Because myeloma guidelines consider only light-chain cast nephropathy a myeloma-defining renal event, other lesions (e.g., MIDD, AL amyloidosis, immunotactoid GN, PGNMID, C3 glomerulopathy, TMA) may be excluded from myeloma diagnosis despite progressive renal risk. MGRS is now WHO-recognized as a clonal disorder and generally warrants clone-directed therapy.<br /><br />Diagnosis typically requires kidney biopsy with proof of light-chain restriction; exceptions include systemic AL amyloidosis with classic renal presentation and light-chain proximal tubulopathy with Fanconi syndrome. New insights include that true fibrillary GN is rarely monoclonal after DNAJB9 testing, and IgG3-PGNMID has very low clone detection, while light-chain PGNMID often has detectable monoclonal gammopathy. A newly described entity is light-chain crystalline podocytopathy, often presenting as collapsing FSGS and sometimes requiring special immunofluorescence techniques.<br /><br />Management emphasizes linking kidney deposits to the same monoclonal protein in blood and the responsible clone, because deep hematologic responses (VGPR/CR) best preserve kidney function and improve transplant outcomes; low eGFR (<20) predicts poor renal recovery. Novel therapies (CAR-T, bispecific antibodies) show rapid, deep responses in refractory AL amyloidosis but carry infectious and immune-toxicity risks. In Q&A, he advises full hematologic workup when MGRS is plausible, but suggests clone hunting is often low-yield in IgG3-PGNMID without detectable monoclonal protein.

Asset Subtitle

Nelson Leung

Meta Tag

Module GLOM

Speaker Nelson Leung

Keywords

monoclonal gammopathy of renal significance (MGRS)

clone-directed therapy

kidney biopsy light-chain restriction

AL amyloidosis

monoclonal immunoglobulin deposition disease (MIDD)

proliferative glomerulonephritis with monoclonal Ig deposits (PGNMID)

CAR-T and bispecific antibodies