The intersection of cardiovascular disease, metabolic disorders and chronic kidney disease represents a complex clinical picture challenging healthcare systems worldwide. Metabolic-dysfunction-associated steatotic liver disease (MASLD) often manifests sequentially or concomitantly with these diseases, and may share underlying mechanisms and risk factors. Growing evidence suggests that new therapies could have benefits across these diseases, but trial sponsors and investigators tend to be reluctant to include patients with comorbidities—particularly liver diseases—in clinical trials. In this Perspective, we call for inclusion of patients with MASLD and measurement of liver outcomes in cardio–kidney–metabolic trials, when data suggest mechanistically plausible benefits and liver and cardiovascular safety. We discuss the implications of this new paradigm for clinical trial design and considerations for regulatory approval. Finally, we outline the challenges to implementing such an approach and provide recommendations for future clinical trial conduct.

心血管疾病、代谢紊乱和慢性肾脏疾病的交叉表现出复杂的临床情况，对全球医疗保健系统提出了挑战。代谢功能障碍相关的脂肪肝病 (MASLD) 通常与这些疾病相继或同时出现，并且可能具有共同的潜在机制和危险因素。越来越多的证据表明，新疗法可能对这些疾病有益，但试验申办者和研究人员往往不愿意将患有合并症（尤其是肝病）的患者纳入临床试验。在本观点中，当数据表明机械上合理的益处以及肝脏和心血管安全性时，我们呼吁将 MASLD 患者纳入心肾代谢试验中并测量肝脏结果。我们讨论了这种新范式对临床试验设计的影响以及监管批准的注意事项。最后，我们概述了实施这种方法的挑战，并为未来临床试验的进行提供建议。