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.

中文翻译：

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肾脏健康和疾病中的性别二态性：机制见解和临床意义


性别是调节人类生理和病理的关键变量。许多疾病不成比例地影响一种性别：自身免疫性疾病，如系统性红斑狼疮，在女性中更常见，但在男性中更严重，而其他疾病如痛风性关节炎和恶性癌症的发病率在男性中更高。除了病理生理学，性也可能影响治疗的疗效;临床试验的参与者仍然以男性为主，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突出特征，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、激素和疗法的反应。这些反应很可能在性别之间有所不同。因此，从基础科学到临床前研究再到临床研究和试验，在转化科学中考虑性别差异变得势在必行。在临床前动物研究或临床试验中，一种性别的代表性不足仍然是一个问题，此类研究的主要报告结果应单独呈现。没有这一点，仍然很难适当和有效地调整肾脏疾病的管理。在这篇综述中，我们对啮齿动物和人类在肾脏健康和疾病方面的性别差异提供了机制见解，强调了在任何临床前动物或临床研究的设计中考虑性别差异的重要性，并就如何优化设计和进行临床前动物研究提出了指导在未来的研究中。