Crystalline κ-light-chain proximal tubulopathy in Waldenström macroglobulinemia with an IgA nephropathy pattern: a case report and systematic review.

Authors

Jun Zhang, Xing Chen, Lijing Yao, Tiekun Li, Xuejuan Sun, Xiuhua Xu, Peijin Bai, Leping Shao, Juan Pei

Published in

Frontiers in immunology. Volume 17. Pages 1942324. Epub Oct 15, 2026.

Abstract

Light-chain proximal tubulopathy (LCPT) is a rare renal manifestation of monoclonal gammopathy that is exceptionally uncommon in Waldenström macroglobulinemia (WM). We report a case of crystalline κ-LCPT in WM and conduct a literature review of WM-associated LCPT and crystal-storing histiocytosis (CSH). A 65-year-old man with a 4-year history of intermittent hematuria and proteinuria developed progressive renal dysfunction. Before admission, myeloperoxidase (MPO)-anti-neutrophil cytoplasmic antibody (ANCA) was strongly positive by qualitative immunoblotting, initially raising concern for ANCA-associated vasculitis. After admission, repeat testing on a separate sample showed only modest MPO-ANCA elevation by chemiluminescence, whereas proteinase 3 (PR3)-ANCA and both P-ANCA and C-ANCA by indirect immunofluorescence were negative; serum immunoglobulin M (IgM) was markedly elevated, and monoclonal IgM-κ was identified in serum and urine. Kidney biopsy demonstrated crystalline κ-LCPT, with κ-predominant light-chain staining in proximal tubular epithelial cells and organized intracytoplasmic crystals on electron microscopy. Concurrent glomerular findings showed an immunoglobulin A (IgA) nephropathy pattern, characterized by strong mesangial IgA/C3 deposition, polytypic glomerular κ and λ staining without light-chain restriction, and corresponding electron-dense deposits. The biopsy showed no active pauci-immune necrotizing or cellular crescentic glomerulonephritis, arguing against ANCA-mediated renal injury. Crystalline material was also identified ultrastructurally within interstitial mononuclear cells, raising but not confirming CSH because histiocytic lineage was not verified by CD68/CD163. Bone marrow examination established WM/LPL with MYD88-L265P positivity. MYD88-L265P places the underlying lymphoplasmacytic clone within the canonical MYD88-interleukin-1 receptor-associated kinase (IRAK)-Bruton tyrosine kinase (BTK)-nuclear factor κB (NF-κB) signaling axis of WM. The discordant MPO-ANCA serology was considered more likely to represent non-specific/paraprotein-associated assay reactivity. Sequential BTK inhibitor therapy (ibrutinib followed by zanubrutinib, with the temporary addition of bortezomib-dexamethasone) achieved sustained hematological response and stable renal function over 49 months of follow-up. Our literature review identified seven eligible published WM-associated LCPT and/or CSH cases, yielding eight cases including the present patient. This case expands the spectrum of WM-associated renal disease by highlighting crystalline κ-LCPT as a rare clone-related tubular lesion and underscores the importance of integrated renal pathological and hematological evaluation in distinguishing clone-related injury from coexisting renal lesions.

PMID:
42959041
Bibliographic data and abstract were imported from PubMed on 30 Oct 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.