Department of Pharmacology and Toxicology, University of Lausanne, Lausanne, Switzerland.
Service of Nephrology, Department of Medicine, Lausanne University Hospital, Lausanne, Switzerland.
Nat Rev Nephrol. 2018 Oct;14(10):626-635. doi: 10.1038/s41581-018-0048-9.
Numerous physiological functions exhibit substantial circadian oscillations. In the kidneys, renal plasma flow, the glomerular filtration rate and tubular reabsorption and/or secretion processes have been shown to peak during the active phase and decline during the inactive phase. These functional rhythms are driven, at least in part, by a self-sustaining cellular mechanism termed the circadian clock. The circadian clock controls different cellular functions, including transcription, translation and protein post-translational modifications (such as phosphorylation, acetylation and ubiquitylation) and degradation. Disruption of the circadian clock in animal models results in the loss of blood pressure control and substantial changes in the circadian pattern of water and electrolyte excretion in the urine. Kidney-specific suppression of the circadian clock in animals implicates both the intrinsic renal and the extrarenal circadian clocks in these pathologies. Alterations in the circadian rhythm of renal functions are associated with the development of hypertension, chronic kidney disease, renal fibrosis and kidney stones. Furthermore, renal circadian clocks might interfere with the pharmacokinetics and/or pharmacodynamics of various drugs and are therefore an important consideration in the treatment of some renal diseases or disorders.
许多生理功能表现出明显的昼夜节律波动。在肾脏中，肾血浆流量、肾小球滤过率以及肾小管重吸收和/或分泌过程已被证明在活动期达到峰值，而在非活动期下降。这些功能节律至少部分是由一种称为生物钟的自我维持的细胞机制驱动的。生物钟控制着不同的细胞功能，包括转录、翻译和蛋白质翻译后修饰（如磷酸化、乙酰化和泛素化）以及降解。在动物模型中破坏生物钟会导致血压失控，以及尿液中水分和电解质排泄的昼夜节律模式发生重大变化。动物中肾脏特异性的生物钟抑制暗示了内在的肾脏和肾脏外生物钟在这些病理中都有作用。肾功能昼夜节律的改变与高血压、慢性肾脏病、肾纤维化和肾结石的发展有关。此外，肾脏生物钟可能会干扰各种药物的药代动力学和/或药效学，因此在治疗某些肾脏疾病或病症时需要考虑这一点。
