Cortisol excess in chronic kidney disease - A review of changes and impact on mortality.
Cortisol excess in chronic kidney disease - A review of changes and impact on mortality.
复制标题
DOI：
10.3389/fendo.2022.1075809
复制
发表时间：
2022
影响因子：
5.2
通讯作者：
Hardy, Rowan S.
中科院分区：
文献类型：
--
作者：
Sagmeister, Michael S.;Harper, Lorraine;Hardy, Rowan S.
关键词：
慢性肾脏病（CKD）描述了任何原因导致的肾功能受损的长期状况。CKD是常见的并且与广泛的并发症相关，包括较高的死亡率、心血管疾病、高血压、胰岛素抵抗、血脂异常、肌肉减少症、骨质疏松症、异常免疫功能、认知损害、情绪障碍和睡眠质量差。糖皮质激素是内源性多效性类固醇激素，其过量产生的发病模式与CKD有相当大的重叠。皮质醇是人体中主要的活性糖皮质激素，其循环水平由几个过程之间的复杂相互作用决定。下丘脑-垂体-肾上腺轴（HPA）调节皮质醇的合成和释放，11β-羟基类固醇脱氢酶介导活性和非活性形式之间的代谢相互转化，循环中的清除取决于肝脏中的不可逆代谢失活，然后通过尿液排泄。慢性应激、炎症状态和CKD的其他方面可以干扰这些过程，通过HPA轴增强皮质醇分泌，并诱导糖皮质激素信号的组织驻留放大。进行性肾损害可进一步影响皮质醇代谢和皮质醇代谢物的尿清除。因此，存在重大的兴趣，以准确地了解CKD中皮质醇的失调及其对不良临床结果的意义。在这篇综述中，我们总结了最新的文献中的内源性糖皮质激素调节慢性肾脏病成人的改变，并评估现有的证据皮质醇作为一个机械驱动器的过度死亡率和发病率。新出现的情况是亚临床皮质醇增多症，皮质醇水平昼夜下降迟钝，负反馈调节受损，皮质醇清除率降低。在终末期肾衰竭患者的观察性研究中报告了皮质醇与校正的全因死亡率之间的相关性，但需要进一步研究来评估皮质醇与CKD临床结局之间的联系。我们对未来的研究提出了建议，包括旨在通过纠正或逆转皮质醇失调来减少CKD并发症的治疗策略。
Chronic kidney disease (CKD) describes the long-term condition of impaired kidney function from any cause. CKD is common and associated with a wide array of complications including higher mortality, cardiovascular disease, hypertension, insulin resistance, dyslipidemia, sarcopenia, osteoporosis, aberrant immune function, cognitive impairment, mood disturbances and poor sleep quality. Glucocorticoids are endogenous pleiotropic steroid hormones and their excess produces a pattern of morbidity that possesses considerable overlap with CKD. Circulating levels of cortisol, the major active glucocorticoid in humans, are determined by a complex interplay between several processes. The hypothalamic-pituitary-adrenal axis (HPA) regulates cortisol synthesis and release, 11β-hydroxysteroid dehydrogenase enzymes mediate metabolic interconversion between active and inactive forms, and clearance from the circulation depends on irreversible metabolic inactivation in the liver followed by urinary excretion. Chronic stress, inflammatory states and other aspects of CKD can disturb these processes, enhancing cortisol secretion via the HPA axis and inducing tissue-resident amplification of glucocorticoid signals. Progressive renal impairment can further impact on cortisol metabolism and urinary clearance of cortisol metabolites. Consequently, significant interest exists to precisely understand the dysregulation of cortisol in CKD and its significance for adverse clinical outcomes. In this review, we summarize the latest literature on alterations in endogenous glucocorticoid regulation in adults with CKD and evaluate the available evidence on cortisol as a mechanistic driver of excess mortality and morbidity. The emerging picture is one of subclinical hypercortisolism with blunted diurnal decline of cortisol levels, impaired negative feedback regulation and reduced cortisol clearance. An association between cortisol and adjusted all-cause mortality has been reported in observational studies for patients with end-stage renal failure, but further research is required to assess links between cortisol and clinical outcomes in CKD. We propose recommendations for future research, including therapeutic strategies that aim to reduce complications of CKD by correcting or reversing dysregulation of cortisol.
登录
查看更多内容
影响因子：
3.5
作者：
Afsar, Baris
通讯作者：
Afsar, Baris
DOI：
10.1053/j.ajkd.2011.03.029
发表时间：
2011-09
期刊：
American journal of kidney diseases : the official journal of the National Kidney Foundation
影响因子：
--
作者：
Brem AS;Morris DJ;Gong R
通讯作者：
Gong R
影响因子：
3.5
作者：
Crawford AA;Bankier S;Altmaier E;Barnes CLK;Clark DW;Ermel R;Friedrich N;van der Harst P;Joshi PK;Karhunen V;Lahti J;Mahajan A;Mangino M;Nethander M;Neumann A;Pietzner M;Sukhavasi K;Wang CA;Bakker SJL;Bjorkegren JLM;Campbell H;Eriksson J;Gieger C;Hayward C;Jarvelin MR;McLachlan S;Morris AP;Ohlsson C;Pennell CE;Price J;Rudan I;Ruusalepp A;Spector T;Tiemeier H;Völzke H;Wilson JF;Michoel T;Timpson NJ;Smith GD;Walker BR;CORtisol NETwork (CORNET) consortium
通讯作者：
CORtisol NETwork (CORNET) consortium
影响因子：
5.4
作者：
Ceccato, F.;Artusi, C.;Scaroni, C.
通讯作者：
Scaroni, C.
影响因子：
3.7
作者：
Buehlmeier, Judith;Remer, Thomas;Heer, Martina
通讯作者：
Heer, Martina