2. Case report
A 64-year-old Japanese man with a history of hypertension, gastric cancer, and mild thrombocytopenia had renal dysfunction (Creatinine 1.5 mg/dL) and hypokalemia 3 years prior and was referred to our nephrologist because of progressive renal impairment and proximal tubular dysfunction. His laboratory data are shown in Table 1. Urinalysis revealed massive proteinuria (2+, 3.6 g/day) without hematuria and the test results for Bence Jones protein were positive. Urinary beta-2 microglobulin (β-2MG) level was markedly elevated to 92,279 ng/mL. Serum potassium and uric acid level was 4.4 mEq/L (under oral potassium supplementation) and 1.9 mg/dL, respectively. The serum creatinine level was 2.81 mg/dL (eGFR 18.7 mL/min/1.73m2). Serum protein electrophoresis showed an M-spike with monoclonal immunoglobulin (Ig)G-κ and elevated free light chain (FLC)- κ level (56.7 mg/dL).
Concerning the renal tubular function, the fractional excretion (FE) of uric acid (FEUA; normal range 4–14%) and potassium (normal range 10–20%) was 50% and 37.5%, respectively, and the tubular reabsorption of phosphate (TURP; normal range 60–90%) was 59%.
A bone marrow examination showed normocellular marrow with 5% plasma cells exhibiting κ light chain clonality. Cytogenic analysis using the G-banding technique showed a normal karyotype, and metaphase fluorescence in situ hybridization revealed a 1q gain of 3% (three copies) without any other high-risk chromosomal abnormalities, including t(4;14)(p16;q32), t(14;16)(q32;q23), or deletion(17p).
Renal biopsy and immunofluorescence analysis revealed that none of the glomeruli showed histological abnormalities, including amyloid or immunocomplex deposition. However, the κ light chain was positive in the proximal renal tubules, and electron microscopy revealed light chain proximal tubulopathy-specific crystals in the proximal tubular epithelial cells (Figure 1).
[18F]Fluorodeoxyglucose positron emission tomography-computed tomography ([18F]FDG PET/CT) scan revealed no additional renal signs of light chain deposition disease or bone lesions suggestive of multiple myeloma.
The clinical course of the patient is shown in Figure 2. Following an established diagnosis of LCPT with monoclonal gammopathy of undetermined significance, bortezomib 1.5 mg/m2, cyclophosphamide 300 mg/m2, and dexamethasone 40 mg (VCd) were administered on days 1, 8, 15, 22. After four treatment cycles, serum κ light chain, and creatinine improved to 24.9 mg/L (pretreatment; 567 mg/L), and 1.87 mg/dL respectively. Improvements in the renal function prompted us to initiate ASCT, and the patient underwent peripheral blood stem cell mobilization with granulocyte colony-stimulating factor (G-CSF) and plerixafor. Subsequently, he received a high dose of melphalan (140 mg/m2) followed by ASCT and achieved successful engraftment without serious complications. One month after ASCT, he achieved a stringent complete response, and serum creatinine level decreased from 3.32 mg/dL to 1.85 mg/dL. In addition, proximal tubular function improved, as evidenced by a reduction in FEUA, elevation of TURP, and resolution of urinary glucose. The patient no longer needed potassium or bicarbonate supplementation. His renal function remained stable for 6 months after ASCT.