Pub Date : 2024-09-02DOI: 10.1038/s41581-024-00888-0
Paris J. Baptiste
{"title":"Reference-trial-informed design to explore treatment effects in trial-underrepresented subgroups","authors":"Paris J. Baptiste","doi":"10.1038/s41581-024-00888-0","DOIUrl":"10.1038/s41581-024-00888-0","url":null,"abstract":"","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"21 1","pages":"6-6"},"PeriodicalIF":28.6,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142118057","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}
Pub Date : 2024-08-29DOI: 10.1038/s41581-024-00887-1
Rasha Shemies
For women with kidney disease of childbearing age, kidney care should feature discussions of pregnancy, including informed counseling and support. Health disparities between regions with different levels of income are undeniable, but special care programs aimed at the early identification and management of patients at risk can greatly decrease the magnitude of the problem.
{"title":"Towards an effective obstetric nephrology care: the Mansoura experience","authors":"Rasha Shemies","doi":"10.1038/s41581-024-00887-1","DOIUrl":"10.1038/s41581-024-00887-1","url":null,"abstract":"For women with kidney disease of childbearing age, kidney care should feature discussions of pregnancy, including informed counseling and support. Health disparities between regions with different levels of income are undeniable, but special care programs aimed at the early identification and management of patients at risk can greatly decrease the magnitude of the problem.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"20 12","pages":"767-767"},"PeriodicalIF":28.6,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142100615","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}
Pub Date : 2024-08-28DOI: 10.1038/s41581-024-00872-8
Martine G. E. Knol, Vera C. Wulfmeyer, Roman-Ulrich Müller, Markus M. Rinschen
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.
{"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}
Pub Date : 2024-08-27DOI: 10.1038/s41581-024-00883-5
Ton J. Rabelink, Gangqi Wang, Johan van der Vlag, Bernard M. van den Berg
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.
组织微环境中的透明质酸（HA）基质通过调节炎症信号、内皮-间质转化和细胞迁移，对维持体内平衡至关重要。在发育过程中，HA 的共价修饰和渗透膨胀会产生机械力，从而启动中肠旋转、血管模式化和分支形态发生。HA 与其主要的细胞表面受体 CD44 一起，在细胞表面建立了一个物理化学支架，促进正常生理所需的生长因子和受体的相互作用和聚集。高分子量 HA、肿瘤坏死因子刺激基因 6、Pentraxin 3 和 CD44 可形成稳定的细胞外基质，促进组织再生并减少炎症。相反，高分子量 HA 被透明质酸酶分解成解聚片段，会引发炎症信号、白细胞迁移和血管生成，导致肾脏疾病中的组织损伤和纤维化。由于透明质酸酶的动态调节和组织特异性功能，针对透明质酸酶代谢的研究具有挑战性。然而，通过靶向 HA 的结合伙伴来调节 HA 基质的功能，有望成为恢复组织稳态和减轻病理过程的一种治疗策略。有必要在这一领域开展进一步的研究，以便针对肾脏和其他以 HA 代谢失调为特征的疾病开发新的治疗方法。
{"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}
Pub Date : 2024-08-27DOI: 10.1038/s41581-024-00890-6
Monica Wang
{"title":"NOX2 dampens TLR7 to protect the kidneys in SLE","authors":"Monica Wang","doi":"10.1038/s41581-024-00890-6","DOIUrl":"10.1038/s41581-024-00890-6","url":null,"abstract":"","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"20 10","pages":"635-635"},"PeriodicalIF":28.6,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142080960","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}
Pub Date : 2024-08-20DOI: 10.1038/s41581-024-00879-1
Population ageing will exacerbate the burden of ageing-related diseases, including chronic kidney disease. Mitigating the effects of this burden will require coordinated, multinational efforts.
人口老龄化将加剧包括慢性肾病在内的老龄相关疾病的负担。减轻这一负担的影响需要多国协调努力。
{"title":"A focus on kidney ageing","authors":"","doi":"10.1038/s41581-024-00879-1","DOIUrl":"10.1038/s41581-024-00879-1","url":null,"abstract":"Population ageing will exacerbate the burden of ageing-related diseases, including chronic kidney disease. Mitigating the effects of this burden will require coordinated, multinational efforts.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"20 9","pages":"557-557"},"PeriodicalIF":28.6,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41581-024-00879-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142007466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-19DOI: 10.1038/s41581-024-00881-7
Azuma Nanamatsu, Larissa de Araújo, Kaice A. LaFavers, Tarek M. El-Achkar
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.
{"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}
Pub Date : 2024-08-13DOI: 10.1038/s41581-024-00884-4
Emilie Lambourg
{"title":"Improving the quality of pharmacoepidemiological studies using the target trial emulation framework","authors":"Emilie Lambourg","doi":"10.1038/s41581-024-00884-4","DOIUrl":"10.1038/s41581-024-00884-4","url":null,"abstract":"","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"20 12","pages":"769-769"},"PeriodicalIF":28.6,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141976222","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}
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