Harvey Brian J, Alvarez de la Rosa Diego
Faculty of Medicine, Royal College of Surgeons in Ireland, RCSI University of Medicine and Health Sciences, Dublin, Ireland.
Centro de Estudios Científicos, Valdivia, Chile.
Nephron. 2025;149(2):77-103. doi: 10.1159/000541352. Epub 2024 Oct 15.
Sex differences exist in kidney physiology and disease which are underpinned by the biological actions of the sex hormones estrogen, progesterone and testosterone. In this review, we present an up-to-date discussion of the hormonal and molecular signalling pathways implicated in sex differences in kidney health and disease.
Estrogen and progesterone have protective effects on renal blood flow, glomerular filtration rate and nephron ion and water reabsorptive processes, whereas testosterone tends to compromise these functions. The biological effects of estrogen appear to be the most important in reinforcing kidney function and protecting against kidney diseases in females. The actions of estrogen are myriad but all tend to bolster kidney physiology to maintain a steady-state and adaptable extracellular fluid volume (ECFV) and blood pressure. Estrogen safeguards ECFV homeostasis by stimulating renal epithelial sodium channel (ENaC) and water channel (AQP2) expression and transport function. Renal maintenance of ECFV within narrow physiological limits is a first-line of defense against hypertension and lowers the risk of cardiovascular disease in women. The estrogenic and XX chromosome basis for a female advantage are evident in a wide range of kidney diseases including acute kidney injury, chronic kidney disease, end-stage kidney disease, diabetic kidney disease, and polycystic kidney disease. The molecular mechanisms involve estrogen regulation of nephron ion and water transport, genetic immunogenic responses, activation of the protective arm of the renin angiotensin-aldosterone system and XX chromosome reinforcement of immune responses. Kidney disease can also predispose patients to cancer and women are protected in renal cancer with lower incidence, morbidity, and mortality than age-matched men with the disease.
This review underscores the importance of incorporating sex-specific considerations into clinical practice and basic research to bridge the gap in understanding and addressing biological sex disparities in kidney disease and renal cancer.
肾脏生理学和疾病存在性别差异，这些差异由性激素雌激素、孕激素和睾酮的生物学作用所支撑。在本综述中，我们对与肾脏健康和疾病性别差异相关的激素和分子信号通路进行了最新讨论。
雌激素和孕激素对肾血流量、肾小球滤过率以及肾单位离子和水的重吸收过程具有保护作用，而睾酮往往会损害这些功能。雌激素的生物学效应在增强女性肾功能和预防肾脏疾病方面似乎最为重要。雌激素的作用多种多样，但都倾向于增强肾脏生理功能，以维持稳态且适应性的细胞外液量（ECFV）和血压。雌激素通过刺激肾上皮钠通道（ENaC）和水通道（AQP2）的表达及转运功能来保障ECFV的稳态。将ECFV维持在狭窄的生理范围内是预防高血压的第一道防线，并降低了女性患心血管疾病的风险。女性优势的雌激素和XX染色体基础在包括急性肾损伤、慢性肾病、终末期肾病、糖尿病肾病和多囊肾病在内的多种肾脏疾病中都很明显。分子机制包括雌激素对肾单位离子和水转运的调节、基因免疫反应、肾素 - 血管紧张素 - 醛固酮系统保护臂的激活以及XX染色体对免疫反应的强化。肾脏疾病还会使患者易患癌症，而女性在肾癌方面受到保护，其发病率、患病率和死亡率均低于同龄男性患者。
本综述强调了在临床实践和基础研究中纳入性别特异性考量的重要性，以弥合在理解和解决肾脏疾病及肾癌中生物性别差异方面的差距。
