Crystalline κ-light-chain proximal tubulopathy is a rare clone-related renal lesion in Waldenström macroglobulinemia; in this case, with a coexisting IgA nephropathy pattern and discordant MPO-ANCA serology, integrated renal pathological and hematological evaluation was key, and sequential BTK inhibitor therapy gave sustained hematological response and stable renal function over 49 months.
A 65-year-old man with WM/LPL was diagnosed with crystalline κ-light-chain proximal tubulopathy on kidney biopsy.
The biopsy also showed a concurrent glomerular IgA nephropathy pattern that was not light-chain restricted.
The initial strongly positive MPO-ANCA result was not supported by repeat testing or histology, and was considered more likely non-specific/paraprotein-associated assay reactivity.
Crystalline material was seen ultrastructurally in interstitial mononuclear cells, raising but not confirming crystal-storing histiocytosis.
Bone marrow examination established WM/LPL with MYD88-L265P positivity.
Sequential BTK inhibitor therapy achieved sustained hematological response and stable renal function over 49 months.
The literature review identified seven eligible published WM-associated LCPT and/or CSH cases, giving eight cases with the present patient.
The authors conclude that crystalline κ-LCPT expands the spectrum of WM-associated renal disease and that integrated renal pathology and hematological evaluation is needed to separate clone-related injury from coexisting renal lesions.
This report describes a 65-year-old man with years of blood and protein in his urine and worsening kidney function. An initial blood test strongly suggested an autoimmune kidney disease (ANCA vasculitis). Further testing and a kidney biopsy showed something different: a rare form of kidney damage in which abnormal protein pieces from a blood cancer called Waldenström macroglobulinemia formed crystals in the kidney's tubule cells. The biopsy also showed a separate, coexisting IgA nephropathy pattern in the filtering units. The odd ANCA result was not confirmed on repeat testing, and the biopsy showed none of the damage expected from ANCA vasculitis. The authors think the first result was likely a false or non-specific reaction caused by the abnormal protein from the blood disorder. The man was treated with drugs that target the cancer cells (ibrutinib, then zanubrutinib, with a temporary course of bortezomib and dexamethasone). His blood disease responded and his kidney function stayed stable for 49 months. The authors also found only seven similar cases in the published literature. This research suggests that when a patient with a blood disorder has kidney disease and confusing test results, a kidney biopsy combined with blood and bone marrow evaluation can help distinguish damage caused by the abnormal cell clone from other kidney diseases occurring alongside it. As a single case report with a small literature review, it cannot show how well the treatment works in general.
Zhang J, Chen X, Yao L, Li T, Sun X, Xu X, et al.. (2026). Crystalline κ-light-chain proximal tubulopathy in Waldenström macroglobulinemia with an IgA nephropathy pattern: a case report and systematic review.. Frontiers in immunology. https://doi.org/10.3389/fimmu.2026.1942324