Steroid-resistant nephrotic syndrome due to immune checkpoint inhibitor-associated focal segmental glomerulosclerosis successfully treated with obinutuzumab

Immune checkpoint inhibitor-associated podocytopathies are rare but clinically relevant renal immune-related adverse events (irAEs). Herein, we describe the case of a recurrent head and neck squamous cell carcinoma (HNSCC) of the tongue that developed refractory nephrotic syndrome following pembrolizumab therapy. A renal biopsy showed severe injury consistent with podocytopathy likely secondary to immune checkpoint inhibitor (ICI) use. Management strategies typically include the use of corticosteroids and permanent discontinuation of the ICI. Despite initial improvements, the patient experienced a course of steroid-resistant nephrotic syndrome (SRNS) requiring therapy with rituximab and ultimately obinutuzumab, eventually resulting in sustained remission. This case underscores the diagnostic ambiguity and management challenges of ICI-associated podocytopathy and suggests a potential role for advanced anti-CD20 therapy in refractory cases.