Next-Generation Bruton’s tyrosine kinase Inhibitors plus Rituximab for Chronic Lymphocytic Leukemia-associated Membranoproliferative Glomerulonephritis: A Case Report

Renal involvement in chronic lymphocytic leukemia (CLL) is rare but clinically significant. Among the various pathological types, membranoproliferative glomerulonephritis (MPGN) is the most common and often presents as nephrotic syndrome. Early recognition of the association between renal lesions and CLL is crucial for guiding treatment and improving both renal and hematologic outcomes.We report two biopsy-proven cases of CLL-associated MPGN successfully treated with next-generation Bruton’s tyrosine kinase inhibitors (BTKis). Both patients presented with nephrotic-range proteinuria. In Case 1, initial treatment with rituximab plus chlorambucil was discontinued due to severe infection and intolerance; the patient subsequently achieved sustained hematologic and renal remission with orelabrutinib monotherapy. In Case 2, zanubrutinib monotherapy led to partial improvement, followed by the addition of rituximab to accelerate proteinuria reduction and enhance renal response. To our knowledge, this is the first report of successful treatment of CLL-associated MPGN with next-generation BTKis. These cases underscore the critical role of kidney biopsy in confirming diagnosis and identifying underlying mechanisms. BTK inhibitors offer a safe and effective backbone for controlling systemic CLL activity, while adjunctive anti-CD20 monoclonal antibodies may further promote renal recovery. This combined approach may serve as a promising strategy for managing this rare but challenging complication.