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).