Department of Physiology and Neuroscience, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA.
Department of Small Animal Clinical Sciences, University of Florida, College of Veterinary Medicine, Gainesville, FL, USA.
Nat Rev Nephrol. 2024 Jan;20(1):21-36. doi: 10.1038/s41581-023-00757-2. Epub 2023 Sep 8.
Mammalian kidneys are specialized to maintain fluid and electrolyte homeostasis. The epithelial transport processes along the renal tubule that match output to input have long been the subject of experimental and theoretical study. However, emerging data have identified a new dimension of investigation: sex. Like most tissues, the structure and function of the kidney is regulated by sex hormones and chromosomes. Available data demonstrate sex differences in the abundance of kidney solute and electrolyte transporters, establishing that renal tubular organization and operation are distinctly different in females and males. Newer studies have provided insights into the physiological consequences of these sex differences. Computational simulations predict that sex differences in transporter abundance are likely driven to optimize reproduction, enabling adaptive responses to the nutritional requirements of serial pregnancies and lactation - normal life-cycle changes that challenge the ability of renal transporters to maintain fluid and electrolyte homeostasis. Later in life, females may also undergo menopause, which is associated with changes in disease risk. Although numerous knowledge gaps remain, ongoing studies will provide further insights into the sex-specific mechanisms of sodium, potassium, acid-base and volume physiology throughout the life cycle, which may lead to therapeutic opportunities.
哺乳动物的肾脏具有维持液体和电解质平衡的功能。长期以来，沿肾小管的上皮转运过程一直是实验和理论研究的主题，这些过程使输出与输入相匹配。然而，新出现的数据确定了一个新的研究维度：性别。与大多数组织一样，肾脏的结构和功能受到性激素和染色体的调节。现有数据表明，肾脏溶质和电解质转运体的丰度存在性别差异，这表明女性和男性的肾小管组织和功能明显不同。新的研究提供了对这些性别差异的生理后果的深入了解。计算模拟预测，转运体丰度的性别差异可能是为了优化繁殖而产生的，使适应连续妊娠和哺乳的营养需求成为可能，这是对肾脏转运体维持液体和电解质平衡的能力的挑战——这些是正常的生命周期变化。在生命后期，女性也可能经历更年期，这与疾病风险的变化有关。尽管仍有许多知识空白，但正在进行的研究将进一步深入了解整个生命周期中钠、钾、酸碱和容量生理学的性别特异性机制，这可能为治疗提供机会。
