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}
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}
{"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}
{"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}
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}
{"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}
{"title":"Lymphocytes and innate immune cells in acute kidney injury and repair","authors":"Kyungho Lee, Hye Ryoun Jang, Hamid Rabb","doi":"10.1038/s41581-024-00875-5","DOIUrl":"10.1038/s41581-024-00875-5","url":null,"abstract":"Acute kidney injury (AKI) is a common and serious disease entity that affects native kidneys and allografts but for which no specific treatments exist. Complex intrarenal inflammatory processes driven by lymphocytes and innate immune cells have key roles in the development and progression of AKI. Many studies have focused on prevention of early injury in AKI. However, most patients with AKI present after injury is already established. Increasing research is therefore focusing on mechanisms of renal repair following AKI and prevention of progression from AKI to chronic kidney disease. CD4+ and CD8+ T cells, B cells and neutrophils are probably involved in the development and progression of AKI, whereas regulatory T cells, double-negative T cells and type 2 innate lymphoid cells have protective roles. Several immune cells, such as macrophages and natural killer T cells, can have both deleterious and protective effects, depending on their subtype and/or the stage of AKI. The immune system not only participates in injury and repair processes during AKI but also has a role in mediating AKI-induced distant organ dysfunction. Targeted manipulation of immune cells is a promising therapeutic strategy to improve AKI outcomes. Here, the authors describe the roles of lymphocytes and innate immune cells in inflammatory responses and repair processes during acute kidney injury (AKI). They also discuss the roles of immune cells in crosstalk pathways that result in AKI-induced distant organ dysfunction.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"20 12","pages":"789-805"},"PeriodicalIF":28.6,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141877445","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}
{"title":"Making advance care planning easier for adults with kidney disease and their clinicians","authors":"Ryan D. McMahan, Rebecca L. Sudore","doi":"10.1038/s41581-024-00871-9","DOIUrl":"10.1038/s41581-024-00871-9","url":null,"abstract":"Advance care planning (ACP) has evolved from a narrow focus on end-of-life preference, such as resuscitation, to a continuum of care planning across the life course. Older adults with kidney disease have high morbidity and mortality, and easy-to-use tools can make ACP easier for patients and clinicians.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"20 9","pages":"564-565"},"PeriodicalIF":28.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141875423","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}