Severe Metabolic Decompensation in Metastatic Sarcomatoid Renal Cell Carcinoma During Immune Checkpoint Inhibitor...

Background and Clinical Significance: Sarcomatoid renal cell carcinoma is a rare and highly aggressive variant of renal cell carcinoma, frequently associated with advanced-stage disease, early metastatic spread, and poor prognosis. Although immune checkpoint inhibitors have improved outcomes in metastatic renal cell carcinoma, particularly in tumors with sarcomatoid differentiation, they may also induce severe immune-related adverse events involving multiple organ systems. Case Presentation: We report the case of a 54-year-old woman with metastatic clear cell renal cell carcinoma with sarcomatoid differentiation, previously treated with nivolumab plus ipilimumab and subsequently with pazopanib, who was admitted with severe dehydration, repeated vomiting, marked asthenia, lower-limb-predominant muscle weakness, and inability to maintain orthostatism. Laboratory investigations revealed severe hyperkalemia, hyponatremia, hypoglycemia, anemia, thrombocytopenia, and prerenal acute kidney injury. The patient had a previous history of severe endocrine immune-related toxicity, including autoimmune hypophysitis and hypothyroidism, which had led to discontinuation of immunotherapy. Following fluid resuscitation, electrolyte correction, and supportive treatment, the metabolic abnormalities resolved and renal function improved significantly. Given the severity of the muscle weakness, a possible immune-mediated neuromuscular adverse event was also considered, although hyperkalemia remained a plausible contributing factor. Conclusions: This case highlights the complex interplay between prior immune checkpoint inhibitor exposure, endocrine dysfunction, metabolic decompensation, and possible neuromuscular involvement in metastatic sarcomatoid renal cell carcinoma. Early recognition, careful differential diagnosis, and multidisciplinary management are essential to prevent rapid clinical deterioration and optimize outcomes in patients with complex immune-related toxicities.