Crystalline form of light chain proximal tubulopathy in multiple myeloma

Light chain proximal tubulopathy (LCPT) is a disease characterized by specific kidney damage due to the accumulation of abnormal monoclonal immunoglobulins (paraproteins, M-proteins), produced by B-cells or plasma cells clones, in the epithelium of the proximal tubules. LCPT is one of the patterns, representing a heterogeneous group of kidney diseases, caused by paraproteinemia [1]. Paraproteinemic nephropathies significantly differ in their clinical manifestations, prognosis, approaches to treatment, as well as in their histological manifestations. Most often, paraproteins are secreted by tumor cells in plasma cell myeloma. However, secretion of paraproteins has been described in B-cell lymphomas; monoclonal immunoglobulins secretion may also be driven by non-malignant B-cell or plasma-cell clones [2]. Kidney pathology in secreting plasma-cell dyscrasias includes several types of damage with different patterns and topographic involvement of the nephron through the deposition of monoclonal immunoglobulins or monoclonal light or heavy chains. LCPT is characterized by inclusions of monoclonal immunoglobulin light chains in the cytoplasm of the proximal tubules [1]. The crystalline form of LCPT is a kidney-limited form with crystal accumulation, and, most commonly, is caused by immunoglobulin kappa light chains [3]. The crystalline form of LCPT is characterized by extensive crystal formation in proximal tubular epithelial cells [1]. Of note, monoclonal immunoglobulins are resistant to proteolysis due to specific amino acid sequences [4]. Patient A, 42 years old, complained of large joint pain and the appearance of “foamy” urine for a year before admission. At admission work-up detected proteinuria up to 4.3 g/L, her serum total protein was 64 g/L, total cholesterol 6.02 mmol/L, and serum creatinine 216-229 µmol/L. After the nephrologist’s consult, the patient was referred to the nephrology unit. Her proteinuria was 1.288 g/day, and her serum creatinine was 146 µmol/L. Further work-up with serology tests ruled out connective tissue disorders, including SLE, ANCA-associated vasculitis, and rheumatism. A kidney biopsy was performed to verify the diagnosis. Microscopic examination revealed 15 otherwise normal glomeruli. The cytoplasm of the convoluted tubules epithelium contained coarse eosinophilic granules, with evidence of necrotic lesions of some epithelial cells: cytosome appearance and detachment from the basement membrane. An immunofluorescent study on fresh frozen sections found 4 glomeruli with negative reactions with antibodies to IgA, IgM, C3c, IgG, C1q, kappa, and lambda light chains. In the tubular epithelium, granular cytoplasmic expression was determined by immunohistochemical study with antibodies to lambda light chains, and no expression with antibodies to kappa light chains. Electron microscopy showed normal glomeruli; the cytoplasm of some epithelial cells and tubular lumens contained inclusions of uneven (low and moderate) electron density, medium or large size, irregularly elongated, diamond-shaped, and leaf-shaped. These findings were compatible with the diagnosis of the crystalline form of proximal light chain tubulopathy. An additional workup found Bence-Jones protein lambda in the urine. The bone marrow smear revealed 21% of plasma cells with signs of dysplasia. The final diagnosis was as follows: Multiple myeloma IIB according to Durie-Salmone, with the secretion of Bence-Jones protein lambda. Light chain proximal tubulopathy, crystalline form, CKD stage G3A. The patient was referred to the hematology unit for chemotherapy. None of the authors declare a conflict of interests.

проксимальная тубулопатия легких цепей, моноклональная гаммапатия, множественная миелома, Light Chain Proximal Tubulopathy (LCPT), monoclonal gammopathy, multiple myeloma

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