Abstract: FR-PO037

Focal and Segmental Glomerulosclerosis (FSGS) in Association with Carfilzomib Therapy

Session Information

Category: Nephrology Education

  • 1302 Fellows and Residents Case Reports

Authors

  • Radhakrishna, Roshni, University of North Carolina, Carrboro, North Carolina, United States
  • Nickeleit, Volker, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
  • Hladik, Gerald A., University of North Carolina at Chapel Hill Kidney Center, Chapel Hill, North Carolina, United States
Background

Carfilzomib is a proteasome inhibitor widely used for treatment of multiple myeloma and monoclonal gammopathies of renal significance (MGRS). Herein, we report a case of new onset FSGS in association with carfilzomib therapy.

Methods

A 63-year-old man with stage G3b chronic kidney disease secondary to biopsy proven monoclonal immunoglobulin deposition disease (MIDD) secondary to monoclonal kappa light chains developed nephrotic range proteinuria during therapy with carfilzomib and dexamethasone. He was initially diagnosed with biopsy-proven MIDD 10 years ago. He was treated with bortezomib and dexamethasone followed by melphalan/prednisone with achievement of a sustained remission over the next 10 years. Over that interval, his proteinuria ranged between 200 to 400 mg/d, decreased from 800 mg/d prior to therapy. His serum free light chain-kappa (SFLC-kappa) level was subsequently found to rise from 7 to 110 mg/dl, prompting therapy with 2 cycles of carfilzomib and dexamethasone. He had an excellent clinical response with a decline in the SFLC-kappa level to 29 mg/dl. Despite this response, he developed increased leg edema with a rise in proteinuria from 400 mg/d to 3700 mg/d (72% albumin). Urine immunoelectrophoresis showed no monoclonal spike. His serum creatinine level increased from 2 to 2.4 mg/dl. He did not have evidence of infection. A kidney biopsy showed focal and segmental glomerulosclerosis with collapsing features without evidence of light chain deposition disease. His proteinuria fell to 1.7 g/d over the next 5 months.

Conclusion

Proteasome inhibitors have had proven efficacy in relapsed/refractory multiple myeloma and MGRS. Carfilzomib is a second generation proteasome inhibitor that previously has been reported to cause thrombotic microangiopathy. The temporal onset of this lesion coincident with carfilzomib therapy raises the possibility of carfilzomib-induced FSGS. Worsening proteinuria despite improvement in SFLCs during carfilzomib therapy should raise suspicion for this lesion. This is the first reported case of carfilzomib-associated FSGS and highlights the importance of ongoing surveillance for renal toxicity of novel therapeutic agents