Pub Date : 2024-03-05DOI: 10.1038/s41581-024-00818-0
Djalila Mekahli, Roman-Ulrich Müller, Matko Marlais, Tanja Wlodkowski, Stefanie Haeberle, Marta López de Argumedo, Carsten Bergmann, Luc Breysem, Carla Fladrowski, Elizabeth P. Henske, Peter Janssens, François Jouret, John Christopher Kingswood, Jean-Baptiste Lattouf, Marc Lilien, Geert Maleux, Micaela Rozenberg, Stefan Siemer, Olivier Devuyst, Franz Schaefer, David J. Kwiatkowski, Olivier Rouvière, John Bissler
Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by the presence of proliferative lesions throughout the body. Management of TSC is challenging because patients have a multifaceted systemic illness with prominent neurological and developmental impact as well as potentially severe kidney, heart and lung phenotypes; however, every organ system can be involved. Adequate care for patients with TSC requires a coordinated effort involving a multidisciplinary team of clinicians and support staff. This clinical practice recommendation was developed by nephrologists, urologists, paediatric radiologists, interventional radiologists, geneticists, pathologists, and patient and family group representatives, with a focus on TSC-associated kidney manifestations. Careful monitoring of kidney function and assessment of kidney structural lesions by imaging enable early interventions that can preserve kidney function through targeted approaches. Here, we summarize the current evidence and present recommendations for the multidisciplinary management of kidney involvement in TSC. Care for patients with tuberous sclerosis complex (TSC) should be coordinated by a multidisciplinary team. This Consensus Statement, which involved input from nephrologists, urologists, geneticists, radiologists, interventional radiologists and pathologists as well as patient representatives, provides an overview of TSC-associated kidney manifestations and outlines current recommendations for the management of kidney involvement in TSC.
{"title":"Clinical practice recommendations for kidney involvement in tuberous sclerosis complex: a consensus statement by the ERKNet Working Group for Autosomal Dominant Structural Kidney Disorders and the ERA Genes & Kidney Working Group","authors":"Djalila Mekahli, Roman-Ulrich Müller, Matko Marlais, Tanja Wlodkowski, Stefanie Haeberle, Marta López de Argumedo, Carsten Bergmann, Luc Breysem, Carla Fladrowski, Elizabeth P. Henske, Peter Janssens, François Jouret, John Christopher Kingswood, Jean-Baptiste Lattouf, Marc Lilien, Geert Maleux, Micaela Rozenberg, Stefan Siemer, Olivier Devuyst, Franz Schaefer, David J. Kwiatkowski, Olivier Rouvière, John Bissler","doi":"10.1038/s41581-024-00818-0","DOIUrl":"10.1038/s41581-024-00818-0","url":null,"abstract":"Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by the presence of proliferative lesions throughout the body. Management of TSC is challenging because patients have a multifaceted systemic illness with prominent neurological and developmental impact as well as potentially severe kidney, heart and lung phenotypes; however, every organ system can be involved. Adequate care for patients with TSC requires a coordinated effort involving a multidisciplinary team of clinicians and support staff. This clinical practice recommendation was developed by nephrologists, urologists, paediatric radiologists, interventional radiologists, geneticists, pathologists, and patient and family group representatives, with a focus on TSC-associated kidney manifestations. Careful monitoring of kidney function and assessment of kidney structural lesions by imaging enable early interventions that can preserve kidney function through targeted approaches. Here, we summarize the current evidence and present recommendations for the multidisciplinary management of kidney involvement in TSC. Care for patients with tuberous sclerosis complex (TSC) should be coordinated by a multidisciplinary team. This Consensus Statement, which involved input from nephrologists, urologists, geneticists, radiologists, interventional radiologists and pathologists as well as patient representatives, provides an overview of TSC-associated kidney manifestations and outlines current recommendations for the management of kidney involvement in TSC.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":null,"pages":null},"PeriodicalIF":41.5,"publicationDate":"2024-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41581-024-00818-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140032194","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 : 2024-03-05DOI: 10.1038/s41581-024-00815-3
Jonathan Haydak, Evren U. Azeloglu
Podocytes form the backbone of the glomerular filtration barrier and are exposed to various mechanical forces throughout the lifetime of an individual. The highly dynamic biomechanical environment of the glomerular capillaries greatly influences the cell biology of podocytes and their pathophysiology. Throughout the past two decades, a holistic picture of podocyte cell biology has emerged, highlighting mechanobiological signalling pathways, cytoskeletal dynamics and cellular adhesion as key determinants of biomechanical resilience in podocytes. This biomechanical resilience is essential for the physiological function of podocytes, including the formation and maintenance of the glomerular filtration barrier. Podocytes integrate diverse biomechanical stimuli from their environment and adapt their biophysical properties accordingly. However, perturbations in biomechanical cues or the underlying podocyte mechanobiology can lead to glomerular dysfunction with severe clinical consequences, including proteinuria and glomerulosclerosis. As our mechanistic understanding of podocyte mechanobiology and its role in the pathogenesis of glomerular disease increases, new targets for podocyte-specific therapeutics will emerge. Treating glomerular diseases by targeting podocyte mechanobiology might improve therapeutic precision and efficacy, with potential to reduce the burden of chronic kidney disease on individuals and health-care systems alike. In this Review, the authors examine the biophysical and biomechanical properties that influence podocyte physiology as they integrate and adapt to stimuli from their dynamic environment within the glomerular capillaries. The authors also discuss how dysregulation and loss of biomechanical resilience in podocytes can contribute to kidney disease.
{"title":"Role of biophysics and mechanobiology in podocyte physiology","authors":"Jonathan Haydak, Evren U. Azeloglu","doi":"10.1038/s41581-024-00815-3","DOIUrl":"10.1038/s41581-024-00815-3","url":null,"abstract":"Podocytes form the backbone of the glomerular filtration barrier and are exposed to various mechanical forces throughout the lifetime of an individual. The highly dynamic biomechanical environment of the glomerular capillaries greatly influences the cell biology of podocytes and their pathophysiology. Throughout the past two decades, a holistic picture of podocyte cell biology has emerged, highlighting mechanobiological signalling pathways, cytoskeletal dynamics and cellular adhesion as key determinants of biomechanical resilience in podocytes. This biomechanical resilience is essential for the physiological function of podocytes, including the formation and maintenance of the glomerular filtration barrier. Podocytes integrate diverse biomechanical stimuli from their environment and adapt their biophysical properties accordingly. However, perturbations in biomechanical cues or the underlying podocyte mechanobiology can lead to glomerular dysfunction with severe clinical consequences, including proteinuria and glomerulosclerosis. As our mechanistic understanding of podocyte mechanobiology and its role in the pathogenesis of glomerular disease increases, new targets for podocyte-specific therapeutics will emerge. Treating glomerular diseases by targeting podocyte mechanobiology might improve therapeutic precision and efficacy, with potential to reduce the burden of chronic kidney disease on individuals and health-care systems alike. In this Review, the authors examine the biophysical and biomechanical properties that influence podocyte physiology as they integrate and adapt to stimuli from their dynamic environment within the glomerular capillaries. The authors also discuss how dysregulation and loss of biomechanical resilience in podocytes can contribute to kidney disease.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":null,"pages":null},"PeriodicalIF":41.5,"publicationDate":"2024-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140039885","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 : 2024-03-04DOI: 10.1038/s41581-024-00826-0
Ruhit Sinha, Michael V. Rocco, Pirouz Daeihagh, Anne E. Staples
Haemodialyser technology has not advanced much in decades, despite its unresolved shortcomings. Sophisticated new computational tools such as high-fidelity surrogate in silico dialyser models could reduce the time and expense of exploring alternative designs, dialysis dose and operating conditions compared with the current gold standard in vitro studies.
{"title":"Innovating dialysis through computational modelling of hollow-fibre haemodialysers","authors":"Ruhit Sinha, Michael V. Rocco, Pirouz Daeihagh, Anne E. Staples","doi":"10.1038/s41581-024-00826-0","DOIUrl":"10.1038/s41581-024-00826-0","url":null,"abstract":"Haemodialyser technology has not advanced much in decades, despite its unresolved shortcomings. Sophisticated new computational tools such as high-fidelity surrogate in silico dialyser models could reduce the time and expense of exploring alternative designs, dialysis dose and operating conditions compared with the current gold standard in vitro studies.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":null,"pages":null},"PeriodicalIF":41.5,"publicationDate":"2024-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140026482","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 : 2024-02-29DOI: 10.1038/s41581-024-00825-1
Ellen F. Carney
{"title":"The renal glucagon receptor is essential to kidney metabolic and homeostatic functions","authors":"Ellen F. Carney","doi":"10.1038/s41581-024-00825-1","DOIUrl":"10.1038/s41581-024-00825-1","url":null,"abstract":"","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":null,"pages":null},"PeriodicalIF":41.5,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139994061","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 : 2024-02-28DOI: 10.1038/s41581-024-00824-2
Ellen F. Carney
{"title":"A CAAR NK cell approach to eliminate pathogenic autoantibody-secreting cells","authors":"Ellen F. Carney","doi":"10.1038/s41581-024-00824-2","DOIUrl":"10.1038/s41581-024-00824-2","url":null,"abstract":"","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":null,"pages":null},"PeriodicalIF":41.5,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139987518","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}
Kidney disease affects more than 10% of the global population and is associated with considerable morbidity and mortality, highlighting a need for new therapeutic options. Engineered nanoparticles for the treatment of kidney diseases (renal nanomedicines) represent one such option, enabling the delivery of targeted therapeutics to specific regions of the kidney. Although they are underdeveloped compared with nanomedicines for diseases such as cancer, findings from preclinical studies suggest that renal nanomedicines may hold promise. However, the physiological principles that govern the in vivo transport and interactions of renal nanomedicines differ from those of cancer nanomedicines, and thus a comprehensive understanding of these principles is needed to design nanomedicines that effectively and specifically target the kidney while ensuring biosafety in their future clinical translation. Herein, we summarize the current understanding of factors that influence the glomerular filtration, tubular uptake, tubular secretion and extrusion of nanoparticles, including size and charge dependency, and the role of specific transporters and processes such as endocytosis. We also describe how the transport and uptake of nanoparticles is altered by kidney disease and discuss strategic approaches by which nanoparticles may be harnessed for the detection and treatment of a variety of kidney diseases. Renal nanomedicines may hold promise for the detection and treatment of a variety of kidney diseases. This Review describes how our understanding of the physiological principles that regulate the glomerular filtration, tubular secretion, luminal tubular uptake and re-elimination of nanoparticles in the kidneys may facilitate the selective targeting of nanomedicines to specific segments of the nephron.
{"title":"Physiological principles underlying the kidney targeting of renal nanomedicines","authors":"Yingyu Huang, Xuhui Ning, Samira Ahrari, Qi Cai, Nilum Rajora, Ramesh Saxena, Mengxiao Yu, Jie Zheng","doi":"10.1038/s41581-024-00819-z","DOIUrl":"10.1038/s41581-024-00819-z","url":null,"abstract":"Kidney disease affects more than 10% of the global population and is associated with considerable morbidity and mortality, highlighting a need for new therapeutic options. Engineered nanoparticles for the treatment of kidney diseases (renal nanomedicines) represent one such option, enabling the delivery of targeted therapeutics to specific regions of the kidney. Although they are underdeveloped compared with nanomedicines for diseases such as cancer, findings from preclinical studies suggest that renal nanomedicines may hold promise. However, the physiological principles that govern the in vivo transport and interactions of renal nanomedicines differ from those of cancer nanomedicines, and thus a comprehensive understanding of these principles is needed to design nanomedicines that effectively and specifically target the kidney while ensuring biosafety in their future clinical translation. Herein, we summarize the current understanding of factors that influence the glomerular filtration, tubular uptake, tubular secretion and extrusion of nanoparticles, including size and charge dependency, and the role of specific transporters and processes such as endocytosis. We also describe how the transport and uptake of nanoparticles is altered by kidney disease and discuss strategic approaches by which nanoparticles may be harnessed for the detection and treatment of a variety of kidney diseases. Renal nanomedicines may hold promise for the detection and treatment of a variety of kidney diseases. This Review describes how our understanding of the physiological principles that regulate the glomerular filtration, tubular secretion, luminal tubular uptake and re-elimination of nanoparticles in the kidneys may facilitate the selective targeting of nanomedicines to specific segments of the nephron.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":null,"pages":null},"PeriodicalIF":41.5,"publicationDate":"2024-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139972762","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 : 2024-02-26DOI: 10.1038/s41581-024-00822-4
Susan J. Allison
{"title":"Pericyte–stem cell crosstalk in ccRCC","authors":"Susan J. Allison","doi":"10.1038/s41581-024-00822-4","DOIUrl":"10.1038/s41581-024-00822-4","url":null,"abstract":"","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":null,"pages":null},"PeriodicalIF":41.5,"publicationDate":"2024-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139967282","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 : 2024-02-26DOI: 10.1038/s41581-024-00821-5
Thomas F. Mueller, Sanjay Nagral
Global inequities and inequalities, human and health-care crises, transplantation successes in the face of limited organ availability, and desperate donors and recipients underlie the backstory of organ trafficking, namely the exploitation of the most vulnerable. Despite the framework set out by the Declaration of Istanbul for the ethical donation and transplantation of organs, organ trafficking remains a global challenge.
{"title":"Organ trafficking — a continuing challenge","authors":"Thomas F. Mueller, Sanjay Nagral","doi":"10.1038/s41581-024-00821-5","DOIUrl":"10.1038/s41581-024-00821-5","url":null,"abstract":"Global inequities and inequalities, human and health-care crises, transplantation successes in the face of limited organ availability, and desperate donors and recipients underlie the backstory of organ trafficking, namely the exploitation of the most vulnerable. Despite the framework set out by the Declaration of Istanbul for the ethical donation and transplantation of organs, organ trafficking remains a global challenge.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":null,"pages":null},"PeriodicalIF":41.5,"publicationDate":"2024-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139972761","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 : 2024-02-26DOI: 10.1038/s41581-024-00817-1
Natalia I. Dmitrieva, Manfred Boehm, Paul H. Yancey, Sofia Enhörning
Body water balance is determined by fundamental homeostatic mechanisms that maintain stable volume, osmolality and the composition of extracellular and intracellular fluids. Water balance is maintained by multiple mechanisms that continuously match water losses through urine, the skin, the gastrointestinal tract and respiration with water gains achieved through drinking, eating and metabolic water production. Hydration status is determined by the state of the water balance. Underhydration occurs when a decrease in body water availability, due to high losses or low gains, stimulates adaptive responses within the water balance network that are aimed at decreasing losses and increasing gains. This stimulation is also accompanied by cardiovascular adjustments. Epidemiological and experimental studies have linked markers of low fluid intake and underhydration — such as increased plasma concentration of vasopressin and sodium, as well as elevated urine osmolality — with an increased risk of new-onset chronic diseases, accelerated aging and premature mortality, suggesting that persistent activation of adaptive responses may be detrimental to long-term health outcomes. The causative nature of these associations is currently being tested in interventional trials. Understanding of the physiological responses to underhydration may help to identify possible mechanisms that underlie potential adverse, long-term effects of underhydration and inform future research to develop preventative and treatment approaches to the optimization of hydration status. A number of epidemiological studies have linked markers of underhydration with an increased risk of adverse health outcomes. This Review provides an overview of the mechanisms that regulate body water balance and the adaptive responses to decreased hydration, and describes current understanding of the physiological consequences of underhydration on health outcomes.
{"title":"Long-term health outcomes associated with hydration status","authors":"Natalia I. Dmitrieva, Manfred Boehm, Paul H. Yancey, Sofia Enhörning","doi":"10.1038/s41581-024-00817-1","DOIUrl":"10.1038/s41581-024-00817-1","url":null,"abstract":"Body water balance is determined by fundamental homeostatic mechanisms that maintain stable volume, osmolality and the composition of extracellular and intracellular fluids. Water balance is maintained by multiple mechanisms that continuously match water losses through urine, the skin, the gastrointestinal tract and respiration with water gains achieved through drinking, eating and metabolic water production. Hydration status is determined by the state of the water balance. Underhydration occurs when a decrease in body water availability, due to high losses or low gains, stimulates adaptive responses within the water balance network that are aimed at decreasing losses and increasing gains. This stimulation is also accompanied by cardiovascular adjustments. Epidemiological and experimental studies have linked markers of low fluid intake and underhydration — such as increased plasma concentration of vasopressin and sodium, as well as elevated urine osmolality — with an increased risk of new-onset chronic diseases, accelerated aging and premature mortality, suggesting that persistent activation of adaptive responses may be detrimental to long-term health outcomes. The causative nature of these associations is currently being tested in interventional trials. Understanding of the physiological responses to underhydration may help to identify possible mechanisms that underlie potential adverse, long-term effects of underhydration and inform future research to develop preventative and treatment approaches to the optimization of hydration status. A number of epidemiological studies have linked markers of underhydration with an increased risk of adverse health outcomes. This Review provides an overview of the mechanisms that regulate body water balance and the adaptive responses to decreased hydration, and describes current understanding of the physiological consequences of underhydration on health outcomes.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":null,"pages":null},"PeriodicalIF":41.5,"publicationDate":"2024-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139972760","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 : 2024-02-06DOI: 10.1038/s41581-024-00806-4
Luca Perico, Giuseppe Remuzzi, Ariela Benigni
Sirtuins (SIRTs) are putative regulators of lifespan in model organisms. Since the initial discovery that SIRTs could promote longevity in nematodes and flies, the identification of additional properties of these proteins has led to understanding of their roles as exquisite sensors that link metabolic activity to oxidative states. SIRTs have major roles in biological processes that are important in kidney development and physiological functions, including mitochondrial metabolism, oxidative stress, autophagy, DNA repair and inflammation. Furthermore, altered SIRT activity has been implicated in the pathophysiology and progression of acute and chronic kidney diseases, including acute kidney injury, diabetic kidney disease, chronic kidney disease, polycystic kidney disease, autoimmune diseases and renal ageing. The renoprotective roles of SIRTs in these diseases make them attractive therapeutic targets. A number of SIRT-activating compounds have shown beneficial effects in kidney disease models; however, further research is needed to identify novel SIRT-targeting strategies with the potential to treat and/or prevent the progression of kidney diseases and increase the average human healthspan. This Review summarizes the roles of sirtuins in kidney development, physiological processes and the pathogenesis of acute and chronic kidney diseases. The authors also highlight the potential of sirtuins as therapeutic targets to limit human kidney disease and renal ageing.
{"title":"Sirtuins in kidney health and disease","authors":"Luca Perico, Giuseppe Remuzzi, Ariela Benigni","doi":"10.1038/s41581-024-00806-4","DOIUrl":"10.1038/s41581-024-00806-4","url":null,"abstract":"Sirtuins (SIRTs) are putative regulators of lifespan in model organisms. Since the initial discovery that SIRTs could promote longevity in nematodes and flies, the identification of additional properties of these proteins has led to understanding of their roles as exquisite sensors that link metabolic activity to oxidative states. SIRTs have major roles in biological processes that are important in kidney development and physiological functions, including mitochondrial metabolism, oxidative stress, autophagy, DNA repair and inflammation. Furthermore, altered SIRT activity has been implicated in the pathophysiology and progression of acute and chronic kidney diseases, including acute kidney injury, diabetic kidney disease, chronic kidney disease, polycystic kidney disease, autoimmune diseases and renal ageing. The renoprotective roles of SIRTs in these diseases make them attractive therapeutic targets. A number of SIRT-activating compounds have shown beneficial effects in kidney disease models; however, further research is needed to identify novel SIRT-targeting strategies with the potential to treat and/or prevent the progression of kidney diseases and increase the average human healthspan. This Review summarizes the roles of sirtuins in kidney development, physiological processes and the pathogenesis of acute and chronic kidney diseases. The authors also highlight the potential of sirtuins as therapeutic targets to limit human kidney disease and renal ageing.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":null,"pages":null},"PeriodicalIF":41.5,"publicationDate":"2024-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139697896","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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