Monoclonal Gammopathy of Renal Significance (MGRS) MGRS • MGRS refers to kidney disease caused by nephrotoxic monoclonal immunoglobulins produced by a clonal B-cell or plasma cell disorder that does not meet criteria for hematologic malignancy but leads to kidney damage. Why Does MGRS Matter? • Occurs in patients with MGUS or smoldering myeloma/lymphoma. • Leads to organ damage, especially kidneys. • Historically underdiagnosed or misclassified as benign. • If untreated, MGRS lesions can progress to end-stage kidney disease or evolve into hematologic malignancies. Epidemiology: • Present in 40–45% of patients with monoclonal gammopathy undergoing kidney biopsy. • More common in older adults, especially males. Clinical Clues: • Nephrotic-range proteinuria or subnephrotic proteinuria with rapid decline in kidney function should raise suspicion for MGRS • Proteinuria >1.5 g/day • Hematuria • Reduced kidney function • Abnormal serum free light-chain ratio Diagnostic Workup: • Kidney biopsy is essential. • Serum/urine protein electrophoresis (SPEP/UPEP) • Immunofixation (SIFE/UIFE) • Free light-chain assay • Bone marrow biopsy • Imaging and cytometry as needed for clone detection • CT/PET imaging may be useful for extramedullary disease or lymphoproliferative clones • Kidney biopsy findings guide subtype classification: organized (e.g., amyloid), non-organized (e.g., LCDD), or no deposits (e.g., C3GN) Pathogenesis: How MGRS Damages Kidneys • Low Tumor Burden, High Toxicity • Mechanisms include: - Amyloid formation (e.g., AL amyloidosis) - Light-chain deposition disease (LCDD) - Crystal formation (e.g., light-chain proximal tubulopathy) - Complement pathway activation (e.g., C3 glomerulopathy) - Cryoglobulin formation causing vasculitis Types of MGRS-Associated Lesions: • Organized Deposits: AL amyloidosis, immunotactoid GN, cryoglobulinemic GN • Non-organized Deposits: LCDD, PGNMID • No Deposits: C3 glomerulopathy, thrombotic microangiopathy Treatment Principles: • Clone-directed therapy is key—not standard immunosuppressives. • Plasma cell clone: Bortezomib, daratumumab • B-cell clone (CD20+): Rituximab-based therapy • Goal: Preserve kidney function and prevent progression. • Transplant consideration: Only after achieving hematologic response. #MGRS #Monoclonal #Gammopathy #Renal #Significance #Diagnosis
