{ "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.", "abstract_shown": true, "affiliations": [ "Department of Nephrology, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University", "The School of Clinical Medicine, Fujian Medical University", "Nanjing Kingmed Center for Clinical Laboratory" ], "article_type": "systematic review", "arxiv": null, "author_total": 9, "authors": [ { "affs": [ 0, 1 ], "name": "Jun Zhang" }, { "affs": [ 0, 1 ], "name": "Xing Chen" }, { "affs": [ 0, 1 ], "name": "Lijing Yao" }, { "affs": [ 2 ], "name": "Tiekun Li" }, { "affs": [ 0, 1 ], "name": "Xuejuan Sun" }, { "affs": [ 0, 1 ], "name": "Xiuhua Xu" }, { "affs": [ 0, 1 ], "name": "Peijin Bai" }, { "affs": [ 0, 1 ], "name": "Leping Shao" }, { "affs": [ 0, 1 ], "name": "Juan Pei" } ], "bibtex": "https://research.draconitic.com/paper/dand1q11784yj.bib", "cited_by": 0, "doi": "10.3389/fimmu.2026.1942324", "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13716615/?tool=EBI", "id": "dand1q11784yj", "issns": [ "1664-3224" ], "landing_url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1942324/full", "language": "eng", "licence": "CC-BY-4.0", "licence_label": "CC BY 4.0", "licence_source": "article", "licence_url": "https://creativecommons.org/licenses/by/4.0/", "metadata_licence": null, "native_subjects": [ [ "heading", "Case Report" ], [ "openalex", "2720|Multiple Myeloma Research and Treatments" ] ], "openalex": "W7222347347", "pdf_url": "https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2026.1942324/pdf", "pmcid": "PMC13716615", "pmid": "42959041", "published": "2026-10-15", "publisher": "Frontiers Media SA", "ris": "https://research.draconitic.com/paper/dand1q11784yj.ris", "sources": [ { "first_seen": "2026-10-30T12:19:17Z", "native_id": "10.3389/fimmu.2026.1942324", "source": "crossref", "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1942324/full" }, { "first_seen": "2026-10-31T00:20:37Z", "native_id": "PMC:PMC13716615", "source": "europepmc", "url": "https://europepmc.org/article/PMC/PMC13716615" }, { "first_seen": "2026-11-01T00:20:36Z", "native_id": "MED:42959041", "source": "europepmc", "url": "https://europepmc.org/article/MED/42959041" }, { "first_seen": "2026-11-01T12:23:52Z", "native_id": "PMC13716615", "source": "pmc", "url": "https://doi.org/10.3389/fimmu.2026.1942324" } ], "subjects": [ { "field": "biology", "origin": "issn:1664-3224", "subfield": "immunology" } ], "title": "Crystalline κ-light-chain proximal tubulopathy in Waldenström macroglobulinemia with an IgA nephropathy pattern: a case report and systematic review", "title_text": "Crystalline κ-light-chain proximal tubulopathy in Waldenström macroglobulinemia with an IgA nephropathy pattern: a case report and systematic review", "type": "peer-reviewed", "updated_at": "2026-11-02T12:21:06Z", "url": "https://research.draconitic.com/paper/dand1q11784yj", "venue": "Frontiers in Immunology", "versions": [] }