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Sleep disorders in chronic kidney disease 慢性肾病患者的睡眠障碍
IF 28.6 1区 医学 Q1 UROLOGY & NEPHROLOGY Pub Date : 2024-05-24 DOI: 10.1038/s41581-024-00848-8
Owen D. Lyons
Sleep disorders are highly prevalent in chronic kidney disease (CKD) but are often under-recognized. Restless legs syndrome, which is common in CKD owing to issues with dopamine metabolism and is exacerbated by iron deficiency and uraemia, can lead to poor sleep quality and increased daytime fatigue. Insomnia is also prevalent in CKD, particularly in patients requiring dialysis, with increased sleep latency and sleep fragmentation being reported. The cause of insomnia in CKD is multifactorial — poor sleep habits and frequent napping during dialysis, uraemia, medications and mood disorders have all been suggested as potential contributing factors. Sleep apnoea and CKD are also now recognized as having a bi-directional relationship. Sleep apnoea is a risk factor for accelerated progression of CKD, and fluid overload, which is associated with kidney failure, can lead to both obstructive and central sleep apnoea. The presence of obstructive sleep apnoea in CKD can exacerbate the already heightened cardiovascular morbidity and mortality in these patients, as well as leading to daytime fatigue and reduced quality of life. Increased awareness, timely diagnosis and appropriate therapeutic interventions are essential to reduce the negative impact of sleep disorders in patients with kidney disease. In this Review, Owen Lyons discusses the diagnosis, epidemiology and pathophysiology of three sleep disorders that commonly affect patients with chronic kidney disease — restless legs syndrome, insomnia and sleep apnoea — and their impact on patient morbidity and mortality.
睡眠障碍在慢性肾脏病(CKD)中非常普遍,但往往未得到充分认识。由于多巴胺代谢问题而在慢性肾脏病中常见的不宁腿综合征,会因缺铁和尿毒症而加重,导致睡眠质量差和日间疲劳加剧。失眠在慢性肾脏病患者中也很普遍,尤其是在需要透析的患者中,据报道睡眠潜伏期和睡眠片段增加。导致慢性肾脏病患者失眠的原因是多方面的--不良的睡眠习惯和透析期间经常打盹、尿毒症、药物和情绪障碍都被认为是潜在的诱因。睡眠呼吸暂停和慢性肾脏病现在也被认为具有双向关系。睡眠呼吸暂停是导致慢性肾脏病加速发展的一个危险因素,而与肾衰竭相关的体液超负荷可导致阻塞性和中枢性睡眠呼吸暂停。慢性肾脏病患者出现阻塞性睡眠呼吸暂停会加剧这些患者本已升高的心血管疾病发病率和死亡率,并导致日间疲劳和生活质量下降。提高认识、及时诊断和适当的治疗干预对于减少睡眠障碍对肾病患者的负面影响至关重要。
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引用次数: 0
Kidney health within the broader non-communicable disease agenda 更广泛的非传染性疾病议程中的肾脏健康问题
IF 28.6 1区 医学 Q1 UROLOGY & NEPHROLOGY Pub Date : 2024-05-17 DOI: 10.1038/s41581-024-00847-9
Slim Slama, Valerie A. Luyckx, Bianca Hemmingsen
Kidney disease is strongly linked with cardiovascular diseases, hypertension, diabetes, infections and other health conditions, as well as social determinants of health and climate change. Consequently, a holistic approach to promote well-being, protect individual health and improve access to quality primary care will support kidney health.
肾脏疾病与心血管疾病、高血压、糖尿病、感染和其他健康状况以及健康的社会决定因素和气候变化密切相关。因此,促进福祉、保护个人健康和改善优质初级保健服务的整体方法将有助于肾脏健康。
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引用次数: 0
Podocyte-targeted therapies — progress and future directions 荚膜细胞靶向疗法--进展与未来方向
IF 28.6 1区 医学 Q1 UROLOGY & NEPHROLOGY Pub Date : 2024-05-09 DOI: 10.1038/s41581-024-00843-z
Kristin Meliambro, John C. He, Kirk N. Campbell
Podocytes are the key target cells for injury across the spectrum of primary and secondary proteinuric kidney disorders, which account for up to 90% of cases of kidney failure worldwide. Seminal experimental and clinical studies have established a causative link between podocyte depletion and the magnitude of proteinuria in progressive glomerular disease. However, no substantial advances have been made in glomerular disease therapies, and the standard of care for podocytopathies relies on repurposed immunosuppressive drugs. The past two decades have seen a remarkable expansion in understanding of the mechanistic basis of podocyte injury, with prospects increasing for precision-based treatment approaches. Dozens of disease-causing genes with roles in the pathogenesis of clinical podocytopathies have been identified, as well as a number of putative glomerular permeability factors. These achievements, together with the identification of novel targets of podocyte injury, the development of potential approaches to harness the endogenous podocyte regenerative potential of progenitor cell populations, ongoing clinical trials of podocyte-specific pharmacological agents and the development of podocyte-directed drug delivery systems, contribute to an optimistic outlook for the future of glomerular disease therapy. In this Review, the authors summarize the mechanistic rationale for current treatments for podocytopathies and for novel podocyte-targeted therapies. They also discuss potential approaches to regenerate podocytes and to develop podocyte-specific drug delivery systems.
荚膜细胞是原发性和继发性蛋白尿肾脏疾病的主要损伤靶细胞,占全球肾衰竭病例的 90%。重要的实验和临床研究已经证实,在进行性肾小球疾病中,荚膜细胞耗竭与蛋白尿程度之间存在因果关系。然而,肾小球疾病的治疗方法并没有取得实质性进展,荚膜细胞病的标准治疗方法依赖于重新定位的免疫抑制药物。过去二十年来,人们对荚膜细胞损伤机理基础的认识有了显著提高,基于精准治疗方法的前景也日益光明。目前已鉴定出数十种在临床荚膜病发病机制中发挥作用的致病基因,以及一些假定的肾小球通透性因子。这些成就,加上荚膜细胞损伤新靶点的确定、利用祖细胞群的内源性荚膜细胞再生潜力的潜在方法的开发、正在进行的荚膜细胞特异性药剂临床试验以及荚膜细胞定向给药系统的开发,使得未来的肾小球疾病治疗前景乐观。
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引用次数: 0
Spatial transcriptomics in health and disease 健康和疾病中的空间转录组学
IF 28.6 1区 医学 Q1 UROLOGY & NEPHROLOGY Pub Date : 2024-05-08 DOI: 10.1038/s41581-024-00841-1
Sanjay Jain, Michael T. Eadon
The ability to localize hundreds of macromolecules to discrete locations, structures and cell types in a tissue is a powerful approach to understand the cellular and spatial organization of an organ. Spatially resolved transcriptomic technologies enable mapping of transcripts at single-cell or near single-cell resolution in a multiplex manner. The rapid development of spatial transcriptomic technologies has accelerated the pace of discovery in several fields, including nephrology. Its application to preclinical models and human samples has provided spatial information about new cell types discovered by single-cell sequencing and new insights into the cell–cell interactions within neighbourhoods, and has improved our understanding of the changes that occur in response to injury. Integration of spatial transcriptomic technologies with other omics methods, such as proteomics and spatial epigenetics, will further facilitate the generation of comprehensive molecular atlases, and provide insights into the dynamic relationships of molecular components in homeostasis and disease. This Review provides an overview of current and emerging spatial transcriptomic methods, their applications and remaining challenges for the field. Spatially resolved transcriptomic technologies enable the mapping of transcripts at single-cell or near single-cell resolution in a multiplex manner. This Review describes current and emerging spatial transcriptomic methods, their applications of relevance to kidney biology and remaining challenges for the field.
将数百种大分子定位到组织中的离散位置、结构和细胞类型的能力是了解器官的细胞和空间组织的有力方法。空间分辨转录本组技术能够以多重方式绘制单细胞或接近单细胞分辨率的转录本图谱。空间转录组技术的快速发展加快了包括肾脏病学在内的多个领域的发现步伐。空间转录组技术在临床前模型和人体样本中的应用提供了单细胞测序发现的新细胞类型的空间信息,以及对邻域内细胞-细胞相互作用的新认识,并提高了我们对损伤时发生的变化的理解。空间转录组技术与蛋白质组学和空间表观遗传学等其他全息方法的整合,将进一步促进综合分子图谱的生成,并为了解平衡和疾病中分子成分的动态关系提供见解。本综述概述了当前和新兴的空间转录组学方法、其应用以及该领域仍面临的挑战。
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引用次数: 0
A patient perspective on kidney disease in the public health agenda 从患者角度看公共卫生议程中的肾病问题
IF 28.6 1区 医学 Q1 UROLOGY & NEPHROLOGY Pub Date : 2024-05-07 DOI: 10.1038/s41581-024-00846-w
Daniel Gallego
Chronic kidney disease is a life-changing diagnosis for millions of people worldwide, as the risk of disease progression and kidney failure creates unbearable uncertainty and limits lifestyle. The devastating impact of advanced kidney disease must be acknowledged in the public health agenda to pave way for improved outcomes for patients at all stages of disease.
对全世界数百万人来说,慢性肾脏病是一个改变命运的诊断,因为疾病进展和肾衰竭的风险带来了难以承受的不确定性,并限制了生活方式。必须在公共卫生议程中承认晚期肾病的破坏性影响,从而为改善各阶段患者的治疗效果铺平道路。
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引用次数: 0
Role of the gut microbiota in the pathogenesis of IgA nephropathy 肠道微生物群在 IgA 肾病发病机制中的作用
IF 41.5 1区 医学 Q1 UROLOGY & NEPHROLOGY Pub Date : 2024-04-29 DOI: 10.1038/s41581-024-00845-x
Ellen F. Carney
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引用次数: 0
Progression and outcomes of rare kidney diseases 罕见肾脏疾病的进展和结果
IF 41.5 1区 医学 Q1 UROLOGY & NEPHROLOGY Pub Date : 2024-04-26 DOI: 10.1038/s41581-024-00844-y
Susan J. Allison
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引用次数: 0
Applications of SGLT2 inhibitors beyond glycaemic control SGLT2 抑制剂在控制血糖之外的应用
IF 28.6 1区 医学 Q1 UROLOGY & NEPHROLOGY Pub Date : 2024-04-26 DOI: 10.1038/s41581-024-00836-y
Daniel V. O’Hara, Carolyn S. P. Lam, John J. V. McMurray, Tae Won Yi, Samantha Hocking, Jessica Dawson, Smriti Raichand, Andrzej S. Januszewski, Meg J. Jardine
Sodium–glucose cotransporter 2 (SGLT2) inhibitors were initially developed for their glucose-lowering effects and have shown a modest glycaemic benefit in people with type 2 diabetes mellitus (T2DM). In the past decade, a series of large, robust clinical trials of these therapies have demonstrated striking beneficial effects for various care goals, transforming the chronic disease therapeutic landscape. Cardiovascular safety studies in people with T2DM demonstrated that SGLT2 inhibitors reduce cardiovascular death and hospitalization for heart failure. Subsequent trials in participants with heart failure with reduced or preserved left ventricular ejection fraction demonstrated that SGLT2 inhibitors have beneficial effects on heart failure outcomes. In dedicated kidney outcome studies, SGLT2 inhibitors reduced the incidence of kidney failure among participants with or without diabetes. Post hoc analyses have suggested a range of other benefits of these drugs in conditions as diverse as metabolic dysfunction-associated steatotic liver disease, kidney stone prevention and anaemia. SGLT2 inhibitors have a generally favourable adverse effect profile, although patient selection and medication counselling remain important. Concerted efforts are needed to better integrate these agents into routine care and support long-term medication adherence to close the gap between clinical trial outcomes and those achieved in the real world. Here, the authors discuss the beneficial effects of sodium–glucose cotransporter 2 (SGLT2) inhibitors for a range of clinical outcomes beyond glucose lowering, including kidney and cardiovascular protection. They also discuss the need for implementation and adherence initiatives to help translate the benefits of these agents into real-world clinical outcomes.
钠-葡萄糖共转运体 2(SGLT2)抑制剂最初是因其降糖作用而开发的,在 2 型糖尿病(T2DM)患者中显示出适度的降糖效果。在过去的十年中,这些疗法的一系列大型、稳健的临床试验显示了对各种治疗目标的显著疗效,改变了慢性病治疗的格局。对 T2DM 患者进行的心血管安全性研究表明,SGLT2 抑制剂可降低心血管死亡和心衰住院率。随后在左心室射血分数降低或保留的心力衰竭患者中进行的试验表明,SGLT2 抑制剂对心力衰竭的治疗效果有利。在专门的肾脏结果研究中,SGLT2 抑制剂降低了患有或不患有糖尿病的参与者的肾衰竭发生率。事后分析表明,这类药物对代谢功能障碍相关性脂肪肝、预防肾结石和贫血等多种疾病也有其他益处。SGLT2 抑制剂的不良反应一般较好,但患者的选择和用药咨询仍很重要。我们需要共同努力,更好地将这些药物纳入常规治疗并支持长期坚持用药,以缩小临床试验结果与实际应用结果之间的差距。
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引用次数: 0
Post-translational modifications in kidney diseases and associated cardiovascular risk 肾脏疾病中的翻译后修饰及相关心血管风险
IF 28.6 1区 医学 Q1 UROLOGY & NEPHROLOGY Pub Date : 2024-04-25 DOI: 10.1038/s41581-024-00837-x
Heidi Noels, Vera Jankowski, Stefan J. Schunk, Raymond Vanholder, Sahir Kalim, Joachim Jankowski
Patients with chronic kidney disease (CKD) are at an increased cardiovascular risk compared with the general population, which is driven, at least in part, by mechanisms that are uniquely associated with kidney disease. In CKD, increased levels of oxidative stress and uraemic retention solutes, including urea and advanced glycation end products, enhance non-enzymatic post-translational modification events, such as protein oxidation, glycation, carbamylation and guanidinylation. Alterations in enzymatic post-translational modifications such as glycosylation, ubiquitination, acetylation and methylation are also detected in CKD. Post-translational modifications can alter the structure and function of proteins and lipoprotein particles, thereby affecting cellular processes. In CKD, evidence suggests that post-translationally modified proteins can contribute to inflammation, oxidative stress and fibrosis, and induce vascular damage or prothrombotic effects, which might contribute to CKD progression and/or increase cardiovascular risk in patients with CKD. Consequently, post-translational protein modifications prevalent in CKD might be useful as diagnostic biomarkers and indicators of disease activity that could be used to guide and evaluate therapeutic interventions, in addition to providing potential novel therapeutic targets. Chronic kidney disease (CKD) is associated with several alterations in protein post-translational modifications. Here, the authors examine the evidence of these alterations, their links with CKD progression and cardiovascular risk in patients with CKD, and their potential clinical applications.
与普通人群相比,慢性肾脏病(CKD)患者的心血管风险更高,这至少部分是由与肾脏病独特相关的机制造成的。在慢性肾脏病患者中,氧化应激和尿潴留溶质(包括尿素和高级糖化终产物)水平的增加会增强非酶翻译后修饰事件,如蛋白质氧化、糖化、氨甲酰化和鸟苷酰化。在慢性肾功能衰竭中还可检测到酶翻译后修饰的改变,如糖基化、泛素化、乙酰化和甲基化。翻译后修饰可改变蛋白质和脂蛋白颗粒的结构和功能,从而影响细胞过程。有证据表明,在慢性肾脏病中,翻译后修饰的蛋白质可导致炎症、氧化应激和纤维化,并诱发血管损伤或促凝血栓作用,这可能会导致慢性肾脏病进展和/或增加慢性肾脏病患者的心血管风险。因此,在慢性肾脏病中普遍存在的翻译后蛋白质修饰可能是有用的诊断生物标志物和疾病活动指标,除了提供潜在的新治疗靶点外,还可用于指导和评估治疗干预措施。
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引用次数: 0
Not every organ ticks the same 并非每个器官都有相同的嘀嗒声
IF 28.6 1区 医学 Q1 UROLOGY & NEPHROLOGY Pub Date : 2024-04-24 DOI: 10.1038/s41581-024-00842-0
Khaoula Talbi, Anette Melk
A new study describes the development of proteomics-based ageing clocks that calculate the biological age of specific organs and define features of extreme ageing associated with age-related diseases. Their findings support the notion that plasma proteins can be used to monitor the ageing rates of specific organs and disease progression.
一项新的研究描述了基于蛋白质组学的老化时钟的开发过程,这种时钟可以计算特定器官的生物年龄,并确定与老年相关疾病有关的极端老化特征。他们的研究结果支持了血浆蛋白可用于监测特定器官老化率和疾病进展的观点。
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引用次数: 0
期刊
Nature Reviews Nephrology
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