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Abstract: TH-PO0833

A Rare Case of Renal AH Amyloidosis Secondary to Chronic Lymphocytic Leukemia Effectively Treated with Bruton Tyrosine Kinase Inhibitors

Session Information

Category: Glomerular Diseases

  • 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

  • Morita, Keisuke, Kyoto Daigaku Daigakuin Igaku Kenkyuka Igakubu, Kyoto, Kyoto Prefecture, Japan
  • Yamamoto, Shinya, Kyoto Daigaku Daigakuin Igaku Kenkyuka Igakubu, Kyoto, Kyoto Prefecture, Japan
  • Kotani, Mina, Kyoto Daigaku Daigakuin Igaku Kenkyuka Igakubu, Kyoto, Kyoto Prefecture, Japan
  • Yanagita, Motoko, Kyoto Daigaku Daigakuin Igaku Kenkyuka Igakubu, Kyoto, Kyoto Prefecture, Japan
Introduction

Chronic lymphocytic leukemia (CLL) is characterized as an indolent hematological malignancy. Notably, patients with CLL rarely develop amyloidosis, which is accompanied by organ dysfunction. Recently, the prognosis of CLL patients has significantly improved owing to Bruton’s tyrosine kinase inhibitors (BTKis). These novel agents specifically target B-cell and chemokine receptors, thereby inhibiting the survival, proliferation, and tissue formation of CLL cells. Here, we report a rare case of renal AH amyloidosis secondary to CLL, effectively treated with BTKis.

Case Description

A 67-year-old male, diagnosed with CLL (Rai stage I, Binet stage A) six years before had been follow-up without active treatment. He was referred to our hospital for hematuria and proteinuria. Laboratory data showed normal kidney function (sCre: 0.86 mg/dL), proteinuria (1.4 g/gCre), and monoclonal lambda free light chain. Kidney biopsy revealed nodular lymphocyte infiltration around small vessels and amorphous material in capillary loops, which were confirmed as amyloid deposition by congo-red staining and electron microscopy. Proteomic analysis based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) identified a truncated portion of variable and constant regions of IgG heavy-chain, consistent with AH amyloidosis. Flow cytometric analysis of kidney tissue revealed a lymphocyte population expressing CD5, CD19, and CD20, suggesting direct kidney infiltration of CLL. Finally, the diagnosis of renal AH amyloidosis with CLL infiltration was confirmed. Ibrutinib, a first-generation BTKi, was initiated. After two years of treatment, however, his kidney function deteriorated (sCre: 1.47 mg/dL) and proteinuria increased (3.3 g/gCre). Second kidney biopsy revealed progression of AH amyloidosis. Therapeutic regimen was changed to acalabrutinib, a second-generation BTKi. After two years from the initiation of acalabrutinib, his kidney function has been maintained (sCre: 1.41 mg/dL) and proteinuria has decreased (1.5 g/gCre).

Discussion

To our knowledge, this is the first report of renal AH amyloidosis secondary to CLL. Our case demonstrated the significance of accurate diagnosis of kidney dysfunction secondary to CLL with kidney biopsy and LC-MS/MS method followed by prompt and continuous treatment with novel agents of BTKis.

Digital Object Identifier (DOI)