A 71 year old man with a history of recent onset hypertension presented to the hospital for evaluation of moderate renal failure (eGFR = 37 ml/min per 1.72 m2) and proteinuria (1.5 g/d) discovered 4 months earlier.
On presentation, he was mildly tachypneic (oxygen saturation 90% while breathing ambient air) and had moderate lower limb edema. Laboratory investigations showed (Table 1): severely reduced eGFR (10 ml/min per 1.73 m2), nephrotic proteinuria (7.0 g/d) and microscopic hematuria with red blood cell casts in the urine sediment; mild hypocalcemia; normal complement levels; negative cryoglobulins; moderately reduced total protein and immunoglobulin G levels; normocytic anemia (hemoglobin, 10.5 g/dl); a small amount (<10%) of lambda monoclonal immunoglobulin on serum immunofixation (k/lambda ratio = 2.1), with negative urine immunofixation.
Real-time ultrasound-guided percutaneous renal biopsy was performed, followed by bone marrow aspirate and biopsy.
Renal tissue specimens were examined by light microscopy, immunofluorescence, and electron microscopy. Light microscopy showed membranoproliferative glomerulonephritis with nodular mesangial expansion, occasional protein thrombi and numerous endocapillary infiltrating mononuclear and polymorphonuclear leukocytes (Figures 4A-C). Immunofluorescence demonstrated positive, coarsely granular, staining for C3 (3+), IgG (2+), C1q (1+) and lambda-light chain (3+) involving glomerular capillary walls and, occasionally, the mesangium, with negative staining for k-light chain (Figures 5A-C). Ultrastructural evaluation showed large subendothelial, intramembranous, and mesangial electron dense deposits composed of microtubules (27-30 nm) with hollow centers, organized in parallel arrays (Figures 6A-C) consistent with immunotactoid glomerulonephritis.
Bone marrow aspirate and biopsy were examined by light microscopy, immunohistochemistry, and flow cytometry, and only showed 6% lambda-restricted plasma cells.
The patient was treated with four cycles (cycle length = 28 days) of cyclophosphamide-bortezomib-dexamethasone regimen and received: cyclophosphamide 200 mg per os on days 1, 8, 15 + bortezomib 1.3 mg/m2 subcutaneously on days 1, 8, 15, 22 + dexamethasone 20 mg per os on days 1, 8, 15. Then, he received 5 cycles (cycle length = 28 days) of bortezomib-dexamethasone regimen: bortezomib 1.3 mg/m2 subcutaneously on days 1, 8, 15, 22 + dexamethasone 20 mg per os on days 1, 8, 15. He also received isoniazid prophylaxis for 6 months due to a positive QuantiFERON-TB Gold test result and acyclovir prophylaxis for 12 months. No adverse effects related to the cytotoxic therapy were observed.
Renal biopsy was repeated after 12 months and showed a significant reduction of the membranoproliferative lesions, disappearance of the capillary leukocyte infiltration and of the protein thrombi, and persistent but less evident nodular mesangial expansion (Figures 4D-F). On immunofluorescence there was less evident glomerular capillary wall and mesangial staining for C3 (2+) with complete disappearance of lambda-light chain deposition (Figures 5D,E). Electron microscopy demonstrated nearly complete disappearance of the subendothelial, intramembranous and mesangial electron dense, microtubular deposits (Figures 6D-F).
The laboratory investigations at 12 and 24 months showed substantial renal function improvement, and normalization of proteinuria, serum k/lambda free light chain concentration, and calcium levels (Table 1).