Case Description
A 66-year-old woman presented to our hematology clinic in 2016 with mild granulocytopenia and anemia. Her history was notable for iron deficiency anemia, vitamin D deficiency and laparascopic hysterectomy, though she was otherwise healthy. Her workup revealed a serum M-protein identified as an IgM κ clone at 0.28 g/dL. Her serum free light chain ratio was elevated at 2.23, with a serum free κ of 22.9 mg/L. She was diagnosed with monoclonal gammopathy of uncertain significance and monitored. In 2018, two years after her initial hematology consultation, she presented to nephrology clinic with acute kidney injury, peripheral edema, and hypertension. She had nephrotic range proteinuria at 6 g/24 hours, hematuria, and her urine studies suggested paraproteinuria. Her serum complement C3 was low at 68 mg/dL. She underwent renal biopsy in April of 2018 which demonstrated immunotactoid glomerulopathy with membranoproliferative glomerulonephritis pattern (Fig 1A and 1B). Immunofluorescence of her renal biopsy showed κ light chain deposition in mesangial and capillary loops, with heavy IgM (Fig 1C) and moderate C3 staining (not shown). Electron microscopy revealed numerous immunotactoid deposits beneath the glomerular basement membrane (Fig 1D). Thioflavin and Congo Red staining were both negative for amyloid. Her serum M-protein burden was unchanged, and her bone marrow biopsy was nondiagnostic. Her bone marrow aspirate flow cytometry did identify a small (<5%) CD20+, CD5-, CD10-, CD23-, B-cell population with κ light chain restriction.
She was re-classified with MGRS and treated with rituximab 375 mg/m2 weekly, for four weeks, given over two separate courses. She experienced stable serum M-protein and free light chain burden, improvement of creatinine clearance and hypertension. However, she continued to have nephrotic syndrome. Her urine albumin/creatinine ratio only showed mild improvement from 8166 mg/g in November of 2018 to 7670 mg/g in June of 2019. Due to her persistent renal dysfunction, we chose to treat with a Waldenstrom’s Macroglobulinemia-inspired regimen consisting of bortezomib, dexamethasone, and rituximab, for a total of 5 cycles3. On this regimen, her serum IgM, κ light chain, and creatinine have all normalized, while her urine albumin/creatinine ratio has improved dramatically to 1307 mg/g at time of this publication (Fig 2).