Abstract
Renal involvement in chronic lymphocytic leukemia (CLL) is uncommon but can lead to significant morbidity. Membranoproliferative glomerulonephritis (MPGN) is among the most frequently reported glomerular lesions associated with CLL and may presents with 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, the patient exhibited monoclonal IgG-κ gammopathy and isolated low serum C3, suggestive of complement-mediated injury without direct immunoglobulin deposition. He achieved sustained hematologic and renal remission with orelabrutinib following early discontinuation of rituximab–chlorambucil due to infection. In Case 2, renal biopsy showed interstitial infiltration by CLL cells and immune complex deposition, supporting a leukemic infiltration and immune-complex mediated mechanism. Zanubrutinib led to clinical improvement, and rituximab was later added to further reduce proteinuria. These cases underscore the critical role of kidney biopsy in clarifying diagnosis and underlying mechanisms. In this case series, the treatment regimen centered on next-generation BTKis enabled patients to achieve concurrent favorable renal and hematologic remission with good tolerability.