Immune Checkpoint Inhibitor-Associated, Pauci-immune Glomerulonephritis with a Novel Therapeutic Approach Using Apheresis, Rituximab, and Avacopan

Introduction: Immune checkpoint inhibitor–associated nephritis (ICI-nephritis) is a known renal immune-related adverse event in patients undergoing immunotherapy. Risk factors include concurrent use of nephrotoxic agents and dual ICI therapy. The incidence of acute kidney injury due to immune checkpoint inhibitors ranges from 2–5%, with acute tubule-interstitial nephritis being the most common etiology. Less common histological findings include pauci-immune glomerulonephritis. Management includes ICI discontinuation and corticosteroids, with escalation to various immunosuppressants in resistant cases. Case Description: We report the case of a 69-year-old with stage IIIB PD -L1 (program death ligand -1) positive squamous cell lung carcinoma undergoing Durvalumab therapy who developed outpatient non-oliguric AKI. Admission creatinine was 3.4 mg/dL, (baseline of 1.1 mg/dL). Urinalysis revealed gross hematuria, pyuria, and protein to creatinine ratio 6.4 mg/mg. Prednisone 1 mg/kg was empirically initiated, with only a partial renal response. Therefore, a kidney biopsy was performed and revealed pauci-immune necrotizing and crescentic glomerulonephritis. PR3 (proteinase 3), MPO (myeloperoxidase), and infectious work up was negative. Treatment included methylprednisolone 500 milligrams X 3 days. followed by a prednisone taper starting at 1mg/kg after addition of avacopan 30 mg twice a day, 5 apheresis sessions, and rituximab 1 gram. At hospital discharge, the patient serum creatinine was 3.93 mg/dL and had not required renal replacement therapy. She was readmitted 2 weeks later with upper respiratory symptoms and diagnosed with CMV viremia, leading to rituximab discontinuation and initiation of valganciclovir. Her ICI therapy was permanently stopped. Renal function remained stable, and the patient was ultimately lost to follow-up. Discussion: This case highlights the diagnostic and therapeutic complexity of ICI-associated pauci-immune glomerulonephritis. Specifically, as it relates to early kidney biopsy in delayed steroid responsiveness, absence of PR3/MPO in ICI pauci-immune disease, and possible treatment strategies with its associated complications.