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Abstract: TH-PO0200

Crescentic Membranous Nephropathy: An Unusual Complication of Immune Checkpoint Inhibitor Therapy

Session Information

Category: Onconephrology

  • 1700 Onconephrology

Authors

  • Youssef, Nada, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States
  • Mamlouk, Omar, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States
  • Mandayam, Sreedhar A., The University of Texas MD Anderson Cancer Center, Houston, Texas, United States
  • Tchakarov, Amanda, The University of Texas Health Science Center at Houston John P and Katherine G McGovern Medical School, Houston, Texas, United States
  • Abudayyeh, Ala, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States
Introduction

Immune checkpoint inhibitors (ICIs) have been implicated in various forms of immune-related nephrotoxicity, with tubulointerstitial nephritis being the most frequent, followed by a range of glomerular pathologies. We herein report the first documented case of crescentic membranous nephropathy - a rare glomerular lesion - in the context of ICI therapy.

Case Description

A 65-year-old male with metastatic renal cell carcinoma presented with a 1 week history of fatigue, abdominal distention, and lower extremity edema. He was maintained on nivolumab and cabozantinib - started 2 months prior to presentation. His past medical history is pertinent for hypertension, history of prostate cancer, hypothyroidism , and hyperlipidemia. Laboratory tests revealed an acute rise in creatinine to 2.77 mg/dL from a baseline of 1.0 mg/dL. Urine studies showed active sediments and nephrotic-range proteinuria (24-hr urine protein: 13.89 g).
Serologic testing for anti-neutrophil cytoplasmic antibodies (ANCA) and anti-glomerular basement membrane (GBM) antibodies were negative. We started the patient on diuretics and pursued a kidney biopsy that was revealing crescentic membranous nephropathy with negative PLA2R staining. Subsequently, the patient received intravenous methylprednisolone (250 mg daily for 3 days), followed by oral prednisone taper, 5 sessions of plasmapheresis, then rituximab infusion.

Discussion

Crescentic membranous nephropathy is a rare entity that has been linked to poor renal outcomes. While it has been associated with ANCA, anti-GBM, or PLA2R positivity, its occurrence in the setting of ICI therapy has not been previously reported.
Our patient represents the first known case of ICI-related crescentic membranous nephropathy. Existing literature suggests that aggressive immunosuppressive therapy - corticosteroids with cyclophosphamide or rituximab, with or without plasmapheresis - may be beneficial. We believe this approach is also reasonable for suspected ICI related crescentic membranous nephropathy. However, even with prompt treatment, a substantial proportion of patients are at risk for progression to chronic kidney disease or end-stage renal disease. Large-scale studies are needed to enhance our understanding and inform future management strategies.

Digital Object Identifier (DOI)