Nature Reviews Nephrology最新文献_第9页

The pathogenesis of IgA nephropathy and implications for treatment IgA 肾病的发病机制和治疗意义

IF 28.6 1区医学

Nature Reviews Nephrology Pub Date : 2024-09-04 DOI: 10.1038/s41581-024-00885-3

Chee Kay Cheung, Suceena Alexander, Heather N. Reich, Haresh Selvaskandan, Hong Zhang, Jonathan Barratt

{"title":"The pathogenesis of IgA nephropathy and implications for treatment","authors":"Chee Kay Cheung, Suceena Alexander, Heather N. Reich, Haresh Selvaskandan, Hong Zhang, Jonathan Barratt","doi":"10.1038/s41581-024-00885-3","DOIUrl":"10.1038/s41581-024-00885-3","url":null,"abstract":"IgA nephropathy (IgAN) is a common form of primary glomerulonephritis and represents an important cause of chronic kidney disease globally, with observational studies indicating that most patients are at risk of developing kidney failure within their lifetime. Several research advances have provided insights into the underlying disease pathogenesis, framed by a multi-hit model whereby an increase in circulating IgA1 that lacks galactose from its hinge region — probably derived from the mucosal immune system — is followed by binding of specific IgG and IgA antibodies, generating immune complexes that deposit within the glomeruli, which triggers inflammation, complement activation and kidney damage. Although treatment options are currently limited, new therapies are rapidly emerging that target different pathways, cells and mediators involved in the disease pathogenesis, including B cell priming in the gut mucosa, the cytokines APRIL and BAFF, plasma cells, complement activation and endothelin pathway activation. As more treatments become available, there is a realistic possibility of transforming the long-term outlook for many individuals with IgAN. IgA nephropathy (IgAN) is thought to result from multiple hits that culminate in immune complex deposition in the kidney. Here, the authors describe the latest insights into the pathogenesis of IgAN and how they have revealed novel therapeutic targets and approaches to this disease.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"21 1","pages":"9-23"},"PeriodicalIF":28.6,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142130690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A novel mechanism of sodium and fluid retention in liver disease 肝病中钠和液体潴留的新机制

IF 28.6 1区医学

Nature Reviews Nephrology Pub Date : 2024-09-03 DOI: 10.1038/s41581-024-00892-4

Ellen F. Carney

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Reference-trial-informed design to explore treatment effects in trial-underrepresented subgroups 参考试验信息设计，探索试验未充分代表的亚组的治疗效果

IF 28.6 1区医学

Nature Reviews Nephrology Pub Date : 2024-09-02 DOI: 10.1038/s41581-024-00888-0

Paris J. Baptiste

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Towards an effective obstetric nephrology care: the Mansoura experience 实现有效的产科肾病护理：曼苏拉的经验

IF 28.6 1区医学

Nature Reviews Nephrology Pub Date : 2024-08-29 DOI: 10.1038/s41581-024-00887-1

Rasha Shemies

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Amino acid metabolism in kidney health and disease 肾脏健康和疾病中的氨基酸代谢

IF 28.6 1区医学

Nature Reviews Nephrology Pub Date : 2024-08-28 DOI: 10.1038/s41581-024-00872-8

Martine G. E. Knol, Vera C. Wulfmeyer, Roman-Ulrich Müller, Markus M. Rinschen

{"title":"Amino acid metabolism in kidney health and disease","authors":"Martine G. E. Knol, Vera C. Wulfmeyer, Roman-Ulrich Müller, Markus M. Rinschen","doi":"10.1038/s41581-024-00872-8","DOIUrl":"10.1038/s41581-024-00872-8","url":null,"abstract":"Amino acids form peptides and proteins and are therefore considered the main building blocks of life. The kidney has an important but under-appreciated role in the synthesis, degradation, filtration, reabsorption and excretion of amino acids, acting to retain useful metabolites while excreting potentially harmful and waste products from amino acid metabolism. A complex network of kidney transporters and enzymes guides these processes and moderates the competing concentrations of various metabolites and amino acid products. Kidney amino acid metabolism contributes to gluconeogenesis, nitrogen clearance, acid–base metabolism and provision of fuel for tricarboxylic acid cycle and urea cycle intermediates, and is thus a central hub for homeostasis. Conversely, kidney disease affects the levels and metabolism of a variety of amino acids. Here, we review the metabolic role of the kidney in amino acid metabolism and describe how different diseases of the kidney lead to aberrations in amino acid metabolism. Improved understanding of the metabolic and communication routes that are affected by disease could provide new mechanistic insights into the pathogenesis of kidney diseases and potentially enable targeted dietary or pharmacological interventions. The kidney has an important role in the handling of amino acids, facilitated by a complex network of kidney transporters and enzymes. This Review provides an overview of the role of the kidney in the synthesis, degradation, filtration, reabsorption and excretion of different amino acids and the relevance of these functions in the context of kidney physiology and disease.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"20 12","pages":"771-788"},"PeriodicalIF":28.6,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142085708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The roles of hyaluronan in kidney development, physiology and disease 透明质酸在肾脏发育、生理和疾病中的作用。

IF 28.6 1区医学

Nature Reviews Nephrology Pub Date : 2024-08-27 DOI: 10.1038/s41581-024-00883-5

Ton J. Rabelink, Gangqi Wang, Johan van der Vlag, Bernard M. van den Berg

{"title":"The roles of hyaluronan in kidney development, physiology and disease","authors":"Ton J. Rabelink, Gangqi Wang, Johan van der Vlag, Bernard M. van den Berg","doi":"10.1038/s41581-024-00883-5","DOIUrl":"10.1038/s41581-024-00883-5","url":null,"abstract":"The hyaluronan (HA) matrix in the tissue microenvironment is crucial for maintaining homeostasis by regulating inflammatory signalling, endothelial–mesenchymal transition and cell migration. During development, covalent modifications and osmotic swelling of HA create mechanical forces that initiate midgut rotation, vascular patterning and branching morphogenesis. Together with its main cell surface receptor, CD44, HA establishes a physicochemical scaffold at the cell surface that facilitates the interaction and clustering of growth factors and receptors that is required for normal physiology. High-molecular-weight HA, tumour necrosis factor-stimulated gene 6, pentraxin 3 and CD44 form a stable pericellular matrix that promotes tissue regeneration and reduces inflammation. By contrast, breakdown of high-molecular-weight HA into depolymerized fragments by hyaluronidases triggers inflammatory signalling, leukocyte migration and angiogenesis, contributing to tissue damage and fibrosis in kidney disease. Targeting HA metabolism is challenging owing to its dynamic regulation and tissue-specific functions. Nonetheless, modulating HA matrix functions by targeting its binding partners holds promise as a therapeutic strategy for restoring tissue homeostasis and mitigating pathological processes. Further research in this area is warranted to enable the development of novel therapeutic approaches for kidney and other diseases characterized by dysregulated HA metabolism. Hyaluronan is a critical component of the extracellular matrix, with key roles in tissue homeostasis, cellular signalling and immune responses. Here, the authors describe the roles of hyaluronan in kidney development, adult kidney physiology and kidney disease.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"20 12","pages":"822-832"},"PeriodicalIF":28.6,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142081026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

NOX2 dampens TLR7 to protect the kidneys in SLE NOX2 可抑制 TLR7，从而保护系统性红斑狼疮患者的肾脏。

IF 28.6 1区医学

Nature Reviews Nephrology Pub Date : 2024-08-27 DOI: 10.1038/s41581-024-00890-6

Monica Wang

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Microglial activation in CKD-associated cognitive decline 与慢性肾功能衰竭相关的认知能力下降中的小胶质细胞活化。

IF 28.6 1区医学

Nature Reviews Nephrology Pub Date : 2024-08-27 DOI: 10.1038/s41581-024-00891-5

Susan J. Allison

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A focus on kidney ageing 关注肾脏老化

IF 28.6 1区医学

Nature Reviews Nephrology Pub Date : 2024-08-20 DOI: 10.1038/s41581-024-00879-1

引用次数: 0

Advances in uromodulin biology and potential clinical applications 尿调节蛋白生物学研究进展及潜在临床应用

IF 28.6 1区医学

Nature Reviews Nephrology Pub Date : 2024-08-19 DOI: 10.1038/s41581-024-00881-7

Azuma Nanamatsu, Larissa de Araújo, Kaice A. LaFavers, Tarek M. El-Achkar

{"title":"Advances in uromodulin biology and potential clinical applications","authors":"Azuma Nanamatsu, Larissa de Araújo, Kaice A. LaFavers, Tarek M. El-Achkar","doi":"10.1038/s41581-024-00881-7","DOIUrl":"10.1038/s41581-024-00881-7","url":null,"abstract":"Uromodulin (also known as Tamm–Horsfall protein) is a kidney-specific glycoprotein secreted bidirectionally into urine and into the circulation, and it is the most abundant protein in normal urine. Although the discovery of uromodulin predates modern medicine, its significance in health and disease has been rather enigmatic. Research studies have gradually revealed that uromodulin exists in multiple forms and has important roles in urinary and systemic homeostasis. Most uromodulin in urine is polymerized into highly organized filaments, whereas non-polymeric uromodulin is detected both in urine and in the circulation, and can have distinct roles. The interactions of uromodulin with the immune system, which were initially reported to be a key role of this protein, are now better understood. Moreover, the discovery that uromodulin is associated with a spectrum of kidney diseases, including acute kidney injury, chronic kidney disease and autosomal-dominant tubulointerstitial kidney disease, has further accelerated investigations into the role of this protein. These discoveries have prompted new questions and ushered in a new era in uromodulin research. Here, we delineate the latest discoveries in uromodulin biology and its emerging roles in modulating kidney and systemic diseases, and consider future directions, including its potential clinical applications. In this Review, the authors examine advances in uromodulin biology, including the existence of non-polymeric forms of the protein, its versatile functions, crosstalk with the immune system, its potential as a biomarker and its role in kidney disease, as well as considering how uromodulin might be targeted therapeutically.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"20 12","pages":"806-821"},"PeriodicalIF":28.6,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142002784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0