From Remedy to Etiology: Pauci-Immune Necrotizing and Crescentic Glomerulonephritis following Immune Checkpoint Inhibitor Therapy

Introduction: Immune checkpoint inhibitors (ICI) block inspections before attacking foreign cells widely used in various cancers. Renal IRAEs (Immune-Related Adverse Events), observed in 2-5% of patients, encompass pathologies like acute interstitial nephritis (AIN) and different glomerulonephritides. Prompt steroid commencement should be done before kidney biopsy following suspected renal IRAEs Case Description: 82-year-old Filipino male was evaluated for experiencing fatigue, lethargy, and nausea persisting for one week. The patient has medical history of non-small cell lung carcinoma, undergoing ICI therapy (nivolumab and ipilimumab). The patient had desquamating generalized painful black skin lesions two months before and showed perivascular dermatitis with eosinophils, raising concerns about a potential drug reaction. Vital signs were within normal limits and examination was unremarkable except for lethargy and skin lesions. The initial laboratory results indicated non-anion gap metabolic acidosis with BUN 149 mg/dL (7-30) and creatinine 8.94 mg/dL (0.7-1.2). His renal functions were within the normal range during baseline assessments conducted three weeks ago. As a result, a diagnosis of acute renal failure was established. Tests were negative for relevant antibodies and infections. Our differential diagnosis included considerations for AIN , immune complex glomerulonephritis, or thrombotic microangiopathy, likely associated with immunotherapy. Patient was initiated on high-dose steroids i.e. methylprednisolone 125 mg daily. The patient exhibited an improvement in next 3 days in urine output and creatinine level to 4.38 mg/dL. Ultimately, a renal biopsy was performed for definative diagnosis, revealing pauci-immune necrotizing and crescentic glomerulonephritis with granulomatous interstitial nephritis and eosinophils. Then he was discharged on oral prednisone 50 mg daily. Hemodialysis was not required throughout the entire hospitalization period. Discussion: Renal IRAE could manifest following the co-administration of drugs such as Proton Pump Inhibitors, NSAIDs, or other nephrotoxic medications. Managing renal IRAEs involves halting ICI therapy and steroids. If no improvement then Mycophenolate Mofetil or monoclonal antibodies like Infliximab may be given.