A RARE CASE OF KIDNEY AH AMYLOIDOSIS INDUCED BY CHRONIC LYMPHOCYTIC LEUKEMIA EFFECTIVELY TREATED WITH BRUTON'S TYROSINE KINASE INHIBITOR

Chronic lymphocytic leukemia (CLL) is generally an indolent hematologic malignancy. The indications for therapeutic interventions depend not only on the hematological stage of CLL but also on the involvement of other organ dysfunctions. Recently, the prognosis of CLL patients has been significantly improved owing to Bruton’s tyrosine kinase inhibitors (BTKis), novel agents specifically targeting B-cell and chemokine receptors to inhibit CLL cells proliferation and tissue infiltration. We present the first reported case of kidney AH amyloidosis caused by CLL, successfully treated with BTKis.

A 67-year-old male was diagnosed with CLL, classified as Rai stage Ⅰ and Binet stage A, six years prior. He has been managed through vigilant monitoring without the initiation of active treatment. He was referred to our hospital for hematuria and proteinuria. The laboratory findings revealed normal kidney function (sCr: 0.86 mg/dL), proteinuria (1.4 g/gCr), and monoclonal lambda free light chain (FLC). Kidney biopsy revealed nodular lymphocyte infiltration, mild mesangial proliferation and subepithelial spicules. Amorphous material was detected in the capillary loop and mesangium, which were positive for direct fast scarlet stain and confirmed as amyloid deposition by 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. Flow cytometric analysis of the kidney tissue revealed a certain lymphocyte population expressing CD5, CD19, and CD20, suggesting direct kidney infiltration of CLL. The diagnosis of kidney AH amyloidosis with CLL infiltration was confirmed. Ibrutinib, a first-generation BTKi, was initiated. Two years after ibrutinib initiation, his serum creatinine had elevated to 1.47 mg/dL and proteinuria had increased to 3.3 g/gCr. The second kidney biopsy revealed improvement in lymphocytic infiltration and partial clearance of amyloid deposition, however, the overall damage to the kidney progressed, evidenced by an increased number of sclerosed glomeruli (from 14% at the first biopsy to 28%) and persistent residual amyloid in the capillary wall and mesangial region. The therapeutic regimen was changed to acalabrutinib, a second-generation BTKi. A further decrease in serum monoclonal lambda protein has been achieved with amelioration of kidney function (serum creatinine of 1.41 mg/dL and proteinuria of 1.5 g/gCr).

CLL occasionally leads to the development of various types of glomerulonephritis, including membranoproliferative glomerulonephritis or AL amyloidosis. However, AH amyloidosis secondary to CLL is extremely rare condition. In the present case, the patient was asymptomatic with respect to CLL itself, and the detection of proteinuria and hematuria prompted further investigation. LC-MS/MS and flow cytometric analysis of the kidney tissue confirmed the presence of CLL-related kidney impairment, prompting the initiation of CLL treatment. Although amyloidosis is usually associated with poor kidney prognosis, the novel agents, BTKis were effective in maintaining kidney function in this case. Especially, a second-generation BTKi resulted in a further decrease in the monoclonal protein levels and preservation of kidney function.

This work was first presented at ASN Kidney Week 2025, and re-submission is permitted by ASN.