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.