Steiger Stefanie, Li Li, Bruchfeld Annette, Stevens Kate I, Moran Sarah M, Floege Jürgen, Caravaca-Fontán Fernando, Mirioglu Safak, Teng Onno Y K, Frangou Eleni, Kronbichler Andreas
Division of Nephrology, Department of Medicine IV, Ludwig-Maximilians-University Hospital Munich, Munich, Germany.
Division of Nephrology, Department of Medicine IV, Ludwig-Maximilians-University Hospital Munich, Munich, Germany.
Kidney Int. 2025 Jan;107(1):51-67. doi: 10.1016/j.kint.2024.08.038. Epub 2024 Oct 28.
Sex is a key variable in the regulation of human physiology and pathology. Many diseases disproportionately affect one sex: autoimmune diseases, such as systemic lupus erythematosus, are more common in women but more severe in men, whereas the incidence of other disorders such as gouty arthritis and malignant cancers is higher in men. Besides the pathophysiology, sex may also influence the efficacy of therapeutics; participants in clinical trials are still predominately men, and the side effects of drugs are more common in women than in men. Sex dimorphism is a prominent feature of kidney physiology and function, and consequently affects the predisposition to many adult kidney diseases. These differences subsequently influence the response to immune stimuli, hormones, and therapies. It is highly likely that these responses differ between the sexes. Therefore, it becomes imperative to consider sex differences in translational science from basic science to preclinical research to clinical research and trials. Under-representation of one sex in preclinical animal studies or clinical trials remains an issue and key reported outcomes of such studies ought to be presented separately. Without this, it remains difficult to tailor the management of kidney disease appropriately and effectively. In this review, we provide mechanistic insights into sex differences in rodents and humans, both in kidney health and disease, highlight the importance of considering sex differences in the design of any preclinical animal or clinical study, and propose guidance on how to optimal design and conduct preclinical animal studies in future research.
性别是人体生理和病理调节中的一个关键变量。许多疾病对某一性别的影响尤为严重：自身免疫性疾病，如系统性红斑狼疮，在女性中更为常见，但在男性中更为严重，而痛风性关节炎和恶性肿瘤等其他疾病的发病率在男性中更高。除了病理生理学，性别也可能影响治疗效果；临床试验的参与者仍然以男性为主，而且药物的副作用在女性中比在男性中更常见。性别二态性是肾脏生理和功能的一个显著特征，因此会影响许多成人肾脏疾病的易感性。这些差异随后会影响对免疫刺激、激素和治疗的反应。很有可能这些反应在性别之间存在差异。因此，在从基础科学到临床前研究再到临床研究和试验的转化科学中考虑性别差异就变得势在必行。临床前动物研究或临床试验中某一性别的代表性不足仍然是一个问题，此类研究报告的关键结果应该分别呈现。没有这些，就仍然难以适当有效地调整肾脏疾病的管理方法。在这篇综述中我们提供了关于啮齿动物和人类在肾脏健康和疾病方面性别差异的机制见解，强调了在任何临床前动物或临床研究设计中考虑性别差异的重要性，并就如何在未来研究中优化设计和开展临床前动物研究提出指导意见。
