Abstract: FR-PO1262
Rare Association of C3 Glomerulonephritis and Chronic Lymphocytic Leukemia
Session Information
- Onconephrology: Diagnostic Dilemmas, Therapy-Related Toxicities, and Clinical Cases
October 23, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Onconephrology
- 1600 Onconephrology
Authors
- Huang, Yuan, Department of Anatomic Pathology Cleveland Clinic, Cleveland, Ohio, United States
- Herlitz, Leal C., Department of Anatomic Pathology Cleveland Clinic, Cleveland, Ohio, United States
- Pai, David Y., Department of Kidney Medicine Cleveland Clinic, Cleveland, Ohio, United States
Introduction
C3 glomerulonephritis (C3GN) is characterized by dominant glomerular C3 deposition due to dysregulation of the alternative complement pathway. In older patients, C3GN is often triggered by monoclonal immunoglobulin (M-protein) mediated functional inhibition of the alternative complement pathway. We report a rare case of C3GN associated with chronic lymphocytic leukemia (CLL) in the absence of M-protein, where targeted hematologic therapy resulted in significant proteinuria reduction.
Case Description
A 75-year-old woman with B-cell CLL (Binet stage 0) on active surveillance for 3 years since initial diagnosis, was referred for increased proteinuria. Urine protein/creatinine ratio (UPCR) was 3.29 mg/mg. Serum creatinine and kappa/lambda ratio were normal. A definitive M-protein was not identified. Peripheral white blood cell (WBC) count was 31.7 k/uL. A renal biopsy demonstrated focal endocapillary proliferative glomerulonephritis on light microscopy. Immunofluorescence revealed 1-2+ mesangial and granular peripheral capillary wall staining for C3 with minimal immunoglobulin deposits. Electron microscopy confirmed mesangial, subendothelial and scattered hump-shaped subepithelial deposits. A brief trial of oral prednisone and mycophenolate was ineffective. Six months post-biopsy, UPCR increased to 12.86 mg/mg and WBC to 162.1 k/uL without signs of concurrent infection. Treatment with zarubrutinib, a Bruton’s tyrosine kinase inhibitor, was initiated. UPCR decreased to 1.46 mg/mg and WBC to 28.7 k/uL after four months of treatment. Shortly thereafter, zanubrutinib was held due to diffuse myalgias. UPCR increased to 3.75 mg/mg and WBC to 72.31 k/uL 7 weeks later. Zanubrutinib was resumed as myalgia symptoms were unchanged. Monitoring of UPCR and WBC remain in progress at the time of this writing.
Discussion
C3GN is most commonly associated with monoclonal gammopathy in older patients. While no M-protein was detected in our case, the dramatic improvement in proteinuria and parallel reduction in WBC following initiation of clone-directed therapy supports a CLL clone as the driver of complement-mediated glomerular injury. The apparent relapse in clinical parameters when zanubrutinib was held also supports our hypothesis that the targeting of underlying hematologic malignancies may serve to achieve renal remission in patients with an associated C3GN.