Where's Walden? Rare Manifestation of Waldenström Macroglobulinemia as Proximal Tubulopathy

Introduction: Waldenström’s macroglobulinemia (WM) is an IgM monoclonal gammopathy that rarely effects the kidneys. We present a patient with WM with proximal tubulopathy that responded to treatment with Rituximab and Zanubrutinib. Case Description: A 67-year-old man with CLL and mixed connective tissue disease manifested with Raynaud’s phenomenon was seen for evaluation of proteinuria. Physical exam was significant for blood pressure of 127/85 and a vasculitic lower extremity rash. Serum creatinine was 1.2 mg/dl and spot urine protein/creatinine ratio (UPCR) was 1.4 g/g. Urinalysis was significant only for proteinuria and he was noted to have a positive urine immunofixation with elevated lambda light chains. A kidney biopsy was performed which showed findings consistent with a proximal tubulopathy and interstitial and perivascular clusters of mononuclear cells with a predominance of lambda staining on immunofluorescence (Figure 1). A bone marrow biopsy was significant for 5-10% CLL/SLL cells and 4% lambda monoclonal plasma cells. Further serologic testing revealed an elevated IgM level of 1493 mg/dl and type I cryoglobulins. A diagnosis of Waldenström’s macroglobulinemia was made and treatment with rituximab was initiated. Two months later, proteinuria had decreased to 0.7 g/g but serum IgM failed to improve, and he developed acrocyanosis. He was started on the Bruton Tyrosine Kinase inhibitor (BTK), Zanubrutinib. Seven months after the initial presentation, UPCR decreased to 0.2g/g with stable kidney function. Discussion: Kidney involvement in WM is rare and most often manifests as amyloidosis or cryoglobulinemic glomerulonephritis. Our patient presented with a light chain proximal tubulopathy without evidence of Fanconi syndrome. Proteinuria resolved by treating his WM with Rituximab and Zanubrutinib, before a hematologic response occurred.Immunofluorescence staining of proximal tubular cells