An Atypical Case of Anti-Glomerular Basement Membrane Disease Induced by Immune Checkpoint Inhibitor Therapy

Introduction: Anti-glomerular basement membrane (anti-GBM) disease is a rare form of glomerulonephritis classically presenting with hematuria and acute kidney injury and in some cases, pulmonary hemorrhage (Goodpasture’s disease). Atypical presentations have been reported in association with immune checkpoint inhibitor (ICI) use. While immune-related adverse events affecting the kidney due to ICIs most commonly result in acute interstitial nephritis, glomerular diseases can rarely occur. Due to lack of information on this disease, management generally mirrors that of classic anti-GBM. We present a case of a young male with a history of metastatic melanoma on nivolumab who presents with rapidly progressive glomerulonephritis and was diagnosed with anti-GBM disease. Case Description: Our patient is a 48 year old male with a history of metastatic melanoma on nivolumab maintenance therapy complicated by immune related thyroiditis and arthritis who presented from the infusion center due to an elevated creatinine on routine labs. On arrival laboratory data revealed an acute kidney injury, microscopic hematuria and an anti-glomerular basement membrane titer of 133 AI. Computed tomography of the abdomen showed peri nephritic stranding and a kidney biopsy was consistent with crescentic glomerulonephritis with ~50% glomerular involvement and weak linear staining of the glomerular basement membrane on immunofluorescence. He was treated with pulse dose methylprednisolone, oral cyclophosphamide and plasmapheresis. His kidney function remained stable with an estimated glomerular filtration rate consistent with chronic kidney disease stage 4 at discharge and he was continued on oral prednisone and cyclophosphamide. Discussion: This case highlights an atypical presentation of anti-GBM disease related to ICI therapy. Standard treatment with corticosteroids, cyclophosphamide, and plasmapheresis was initiated. Previous reports describe variable therapeutic approaches and outcomes, with many patients progressing to requiring dialysis. Interestingly, treatment intensity has not consistently correlated with renal outcomes. Given our patient's delayed presentation following initial exposure to nivolumab and weak linear staining on biopsy, we question whether conventional management strategies should be reevaluated in select cases of ICI-associated anti-GBM disease.