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However, these advancements come with a significant challenge: the management of adverse effects, which can impair patients\u2019 quality of life and lead to therapy discontinuation. This review explores the prevalence, mechanisms, and management of gastrointestinal (GI) toxicity associated with immunotherapy combinations for mRCC from the gastroenterologist\u2019s perspective. Diarrhea, colitis, nausea, and vomiting are the most frequently reported adverse events, often necessitating a multidisciplinary approach for timely diagnosis and intervention to mitigate risks and ensure therapeutic continuity. We highlight the management strategies, ranging from symptomatic treatment and dietary modifications to advanced therapies for severe cases, even discussing the emerging approaches for refractory cases. 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