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Abstract: SA-PO0894

Dasatinib-Associated Membranous-Like Glomerulopathy with Masked IgG Kappa Deposits

Session Information

Category: Glomerular Diseases

  • 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

  • Kumar, Parth, Stanford Medicine, Palo Alto, California, United States
  • Kambham, Neeraja, Stanford Medicine, Palo Alto, California, United States
  • Abra, Graham E., Stanford Medicine, Palo Alto, California, United States
Introduction

Membranous-like glomerulopathy with masked IgG kappa deposits (MGMID) is a rare form of glomerular injury characterized by monoclonal IgG deposits that are only detectable after antigen retrieval. This is a case of MGMID associated with dasatinib therapy in a patient treated for chronic myeloid leukemia (CML).

Case Description

A 23-year-old male with morbid obesity and no significant medical history presented with findings suspicious for CML. Bone marrow biopsy confirmed CML and cytogenetic analysis demonstrated the characteristic t(9;22) translocation with BCR-ABL fusion gene. He was subsequently started on dasatinib, achieving normalization of the white blood cell count and a complete molecular response. Five months later, the patient reported "foamy urine" without other symptoms. Laboratory evaluation revealed a urine protein-to-creatinine ratio of 778 mg/g. Urinalysis showed 3+ protein and 1+ blood, with a serum creatinine of 0.9 mg/dL. Serologic evaluation was negative or normal, including complement levels (C3/C4), ANA, ANCA, anti-GBM, anti-PLA2R antibodies, serum protein electrophoresis (SPEP), and serum free light chain (SFLC) ratio. Kidney biopsy demonstrated mild segmental mesangial expansion and hypercellularity, with global granular mesangial and capillary wall deposits positive for C3 (2+) only. Paraffin immunofluorescence with antigen retrieval revealed masked IgG kappa staining (1+) in mesangial and subepithelial regions, as confirmed by electron microscopy. Dasatinib was discontinued and replaced with bosutinib, resulting in subsequent improvement of proteinuria.

Discussion

Dasatinib, a second generation tyrosine kinase inhibitor, has been associated with proteinuria, acute tubular necrosis, and thrombotic microangiopathy. Although MGMID has been associated with hematologic malignancies, the temporal relationship between dasatinib initiation and the onset of proteinuria, along with improvement after drug discontinuation, strongly suggests dasatinib as the causative agent in this case. Furthermore, the patient's CML remained well-controlled, with decreasing BCR-ABL fusion gene levels despite worsening proteinuria, making CML an unlikely cause. This case highlights dasatinib as a potential cause of MGMID and underscores the importance of considering drug-induced etiologies in patients presenting with proteinuria during tyrosine kinase inhibitor therapy.

Digital Object Identifier (DOI)