Pub Date : 2024-05-07DOI: 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.
{"title":"A patient perspective on kidney disease in the public health agenda","authors":"Daniel Gallego","doi":"10.1038/s41581-024-00846-w","DOIUrl":"10.1038/s41581-024-00846-w","url":null,"abstract":"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.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":null,"pages":null},"PeriodicalIF":28.6,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140845166","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 : 2024-04-29DOI: 10.1038/s41581-024-00845-x
Ellen F. Carney
{"title":"Role of the gut microbiota in the pathogenesis of IgA nephropathy","authors":"Ellen F. Carney","doi":"10.1038/s41581-024-00845-x","DOIUrl":"10.1038/s41581-024-00845-x","url":null,"abstract":"","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":null,"pages":null},"PeriodicalIF":41.5,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140814867","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 : 2024-04-26DOI: 10.1038/s41581-024-00844-y
Susan J. Allison
{"title":"Progression and outcomes of rare kidney diseases","authors":"Susan J. Allison","doi":"10.1038/s41581-024-00844-y","DOIUrl":"10.1038/s41581-024-00844-y","url":null,"abstract":"","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":null,"pages":null},"PeriodicalIF":41.5,"publicationDate":"2024-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140648693","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 : 2024-04-26DOI: 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.
{"title":"Applications of SGLT2 inhibitors beyond glycaemic control","authors":"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","doi":"10.1038/s41581-024-00836-y","DOIUrl":"10.1038/s41581-024-00836-y","url":null,"abstract":"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.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":null,"pages":null},"PeriodicalIF":28.6,"publicationDate":"2024-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140648667","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 : 2024-04-25DOI: 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.
{"title":"Post-translational modifications in kidney diseases and associated cardiovascular risk","authors":"Heidi Noels, Vera Jankowski, Stefan J. Schunk, Raymond Vanholder, Sahir Kalim, Joachim Jankowski","doi":"10.1038/s41581-024-00837-x","DOIUrl":"10.1038/s41581-024-00837-x","url":null,"abstract":"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.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":null,"pages":null},"PeriodicalIF":28.6,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140642319","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 : 2024-04-24DOI: 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.
{"title":"Not every organ ticks the same","authors":"Khaoula Talbi, Anette Melk","doi":"10.1038/s41581-024-00842-0","DOIUrl":"10.1038/s41581-024-00842-0","url":null,"abstract":"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.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":null,"pages":null},"PeriodicalIF":28.6,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140639752","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 : 2024-04-24DOI: 10.1038/s41581-024-00838-w
Bianca A. Nguyen, Matthew R. Alexander, David G. Harrison
Hypertension is a leading risk factor for morbidity and mortality worldwide. Despite current anti-hypertensive therapies, most individuals with hypertension fail to achieve adequate blood pressure control. Moreover, even with adequate control, a residual risk of cardiovascular events and associated organ damage remains. These findings suggest that current treatment modalities are not addressing a key element of the underlying pathology. Emerging evidence implicates immune cells as key mediators in the development and progression of hypertension. In this Review, we discuss our current understanding of the diverse roles of innate and adaptive immune cells in hypertension, highlighting key findings from human and rodent studies. We explore mechanisms by which these immune cells promote hypertensive pathophysiology, shedding light on their multifaceted involvement. In addition, we highlight advances in our understanding of autoimmunity, HIV and immune checkpoints that provide valuable insight into mechanisms of chronic and dysregulated inflammation in hypertension. This Review outlines the roles of innate and adaptive immune cells in hypertension. The authors discuss the mechanisms and important properties of immune cells that contribute to hypertension pathogenesis, such as memory and plasticity.
{"title":"Immune mechanisms in the pathophysiology of hypertension","authors":"Bianca A. Nguyen, Matthew R. Alexander, David G. Harrison","doi":"10.1038/s41581-024-00838-w","DOIUrl":"10.1038/s41581-024-00838-w","url":null,"abstract":"Hypertension is a leading risk factor for morbidity and mortality worldwide. Despite current anti-hypertensive therapies, most individuals with hypertension fail to achieve adequate blood pressure control. Moreover, even with adequate control, a residual risk of cardiovascular events and associated organ damage remains. These findings suggest that current treatment modalities are not addressing a key element of the underlying pathology. Emerging evidence implicates immune cells as key mediators in the development and progression of hypertension. In this Review, we discuss our current understanding of the diverse roles of innate and adaptive immune cells in hypertension, highlighting key findings from human and rodent studies. We explore mechanisms by which these immune cells promote hypertensive pathophysiology, shedding light on their multifaceted involvement. In addition, we highlight advances in our understanding of autoimmunity, HIV and immune checkpoints that provide valuable insight into mechanisms of chronic and dysregulated inflammation in hypertension. This Review outlines the roles of innate and adaptive immune cells in hypertension. The authors discuss the mechanisms and important properties of immune cells that contribute to hypertension pathogenesis, such as memory and plasticity.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":null,"pages":null},"PeriodicalIF":28.6,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140639953","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}
Clinical algorithms that are used to guide medical decision-making often include sex as a variable. However, binary considerations of sex and/or gender might introduce bias due to potentially inaccurate assumptions about sex and gender-specific physiology, hormones and exposures. An equity-focused approach to sex and gender is essential when using clinical algorithms to ensure health equity across populations.
{"title":"Considerations of sex as a binary variable in clinical algorithms","authors":"Dinushika Mohottige, Samira Farouk, Tonia Poteat, Asa Radix, Selma Feldman Witchel","doi":"10.1038/s41581-024-00840-2","DOIUrl":"10.1038/s41581-024-00840-2","url":null,"abstract":"Clinical algorithms that are used to guide medical decision-making often include sex as a variable. However, binary considerations of sex and/or gender might introduce bias due to potentially inaccurate assumptions about sex and gender-specific physiology, hormones and exposures. An equity-focused approach to sex and gender is essential when using clinical algorithms to ensure health equity across populations.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":null,"pages":null},"PeriodicalIF":41.5,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140637530","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 : 2024-04-19DOI: 10.1038/s41581-024-00835-z
Alexander Staruschenko, R. Todd Alexander, Michael J. Caplan, Daria V. Ilatovskaya
The kidney plays a pivotal role in regulating calcium levels within the body. Approximately 98% of the filtered calcium is reabsorbed in the nephron, and this process is tightly controlled to maintain calcium homeostasis, which is required to facilitate optimal bone mineralization, preserve serum calcium levels within a narrow range, and support intracellular signalling mechanisms. The maintenance of these functions is attributed to a delicate balance achieved by various calcium channels, transporters, and calcium-binding proteins in renal cells. Perturbation of this balance due to deficiency or dysfunction of calcium channels and calcium-binding proteins can lead to severe complications. For example, polycystic kidney disease is linked to aberrant calcium transport and signalling. Furthermore, dysregulation of calcium levels can promote the formation of kidney stones. This Review provides an updated description of the key aspects of calcium handling in the kidney, focusing on the function of various calcium channels and the physiological stimuli that control these channels or are communicated through them. A discussion of the role of calcium as an intracellular second messenger and the pathophysiology of renal calcium dysregulation, as well as a summary of gaps in knowledge and future prospects, are also included. Calcium reabsorption along the nephron is essential for calcium homeostasis and whole-body electrolyte balance. Here, Staruschenko et al. highlight signalling pathways and molecules involved in renal calcium handling in health and disease, and discuss progress in the integration of systems-level and molecular understanding of calcium transport and regulation.
{"title":"Calcium signalling and transport in the kidney","authors":"Alexander Staruschenko, R. Todd Alexander, Michael J. Caplan, Daria V. Ilatovskaya","doi":"10.1038/s41581-024-00835-z","DOIUrl":"10.1038/s41581-024-00835-z","url":null,"abstract":"The kidney plays a pivotal role in regulating calcium levels within the body. Approximately 98% of the filtered calcium is reabsorbed in the nephron, and this process is tightly controlled to maintain calcium homeostasis, which is required to facilitate optimal bone mineralization, preserve serum calcium levels within a narrow range, and support intracellular signalling mechanisms. The maintenance of these functions is attributed to a delicate balance achieved by various calcium channels, transporters, and calcium-binding proteins in renal cells. Perturbation of this balance due to deficiency or dysfunction of calcium channels and calcium-binding proteins can lead to severe complications. For example, polycystic kidney disease is linked to aberrant calcium transport and signalling. Furthermore, dysregulation of calcium levels can promote the formation of kidney stones. This Review provides an updated description of the key aspects of calcium handling in the kidney, focusing on the function of various calcium channels and the physiological stimuli that control these channels or are communicated through them. A discussion of the role of calcium as an intracellular second messenger and the pathophysiology of renal calcium dysregulation, as well as a summary of gaps in knowledge and future prospects, are also included. Calcium reabsorption along the nephron is essential for calcium homeostasis and whole-body electrolyte balance. Here, Staruschenko et al. highlight signalling pathways and molecules involved in renal calcium handling in health and disease, and discuss progress in the integration of systems-level and molecular understanding of calcium transport and regulation.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":null,"pages":null},"PeriodicalIF":28.6,"publicationDate":"2024-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140621675","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 : 2024-04-17DOI: 10.1038/s41581-024-00834-0
Christian Hinze, Svjetlana Lovric, Philip F. Halloran, Jonathan Barasch, Kai M. Schmidt-Ott
The kidney epithelium, with its intricate arrangement of highly specialized cell types, constitutes the functional core of the organ. Loss of kidney epithelium is linked to the loss of functional nephrons and a subsequent decline in kidney function. In kidney transplantation, epithelial injury signatures observed during post-transplantation surveillance are strong predictors of adverse kidney allograft outcomes. However, epithelial injury is currently neither monitored clinically nor addressed therapeutically after kidney transplantation. Several factors can contribute to allograft epithelial injury, including allograft rejection, drug toxicity, recurrent infections and postrenal obstruction. The injury mechanisms that underlie allograft injury overlap partially with those associated with acute kidney injury (AKI) and chronic kidney disease (CKD) in the native kidney. Studies using advanced transcriptomic analyses of single cells from kidney or urine have identified a role for kidney injury-induced epithelial cell states in exacerbating and sustaining damage in AKI and CKD. These epithelial cell states and their associated expression signatures are also observed in transplanted kidney allografts, suggesting that the identification and characterization of transcriptomic epithelial cell states in kidney allografts may have potential clinical implications for diagnosis and therapy. This Review describes parallels in the injury mechanisms that underlie acute kidney injury, chronic kidney disease and allograft injury, and explains how our understanding of the molecular changes that occur in epithelia in the context of kidney disease may contribute to the therapeutic targeting of specific epithelial cell phenotypes for the treatment of transplantation complications.
肾上皮细胞由高度特化的细胞类型组成，排列错综复杂，是器官的功能核心。肾上皮的缺失与功能性肾小球的缺失以及随后肾功能的下降有关。在肾移植中，移植后监测期间观察到的上皮损伤特征是肾移植不良预后的有力预测因素。然而，目前临床上既不监测上皮损伤，也不对肾移植后的上皮损伤进行治疗。导致异体移植物上皮损伤的因素有多种，包括异体移植物排斥反应、药物毒性、复发性感染和肾移植后梗阻。异体移植损伤的损伤机制与原肾急性肾损伤（AKI）和慢性肾病（CKD）的损伤机制部分重叠。通过对肾脏或尿液中的单细胞进行先进的转录组学分析，研究发现肾脏损伤诱导的上皮细胞状态在加重和维持 AKI 和 CKD 损伤中的作用。这些上皮细胞状态及其相关的表达特征在异体肾移植中也能观察到，这表明识别和描述异体肾移植上皮细胞状态的转录组可能对诊断和治疗具有潜在的临床意义。
{"title":"Epithelial cell states associated with kidney and allograft injury","authors":"Christian Hinze, Svjetlana Lovric, Philip F. Halloran, Jonathan Barasch, Kai M. Schmidt-Ott","doi":"10.1038/s41581-024-00834-0","DOIUrl":"10.1038/s41581-024-00834-0","url":null,"abstract":"The kidney epithelium, with its intricate arrangement of highly specialized cell types, constitutes the functional core of the organ. Loss of kidney epithelium is linked to the loss of functional nephrons and a subsequent decline in kidney function. In kidney transplantation, epithelial injury signatures observed during post-transplantation surveillance are strong predictors of adverse kidney allograft outcomes. However, epithelial injury is currently neither monitored clinically nor addressed therapeutically after kidney transplantation. Several factors can contribute to allograft epithelial injury, including allograft rejection, drug toxicity, recurrent infections and postrenal obstruction. The injury mechanisms that underlie allograft injury overlap partially with those associated with acute kidney injury (AKI) and chronic kidney disease (CKD) in the native kidney. Studies using advanced transcriptomic analyses of single cells from kidney or urine have identified a role for kidney injury-induced epithelial cell states in exacerbating and sustaining damage in AKI and CKD. These epithelial cell states and their associated expression signatures are also observed in transplanted kidney allografts, suggesting that the identification and characterization of transcriptomic epithelial cell states in kidney allografts may have potential clinical implications for diagnosis and therapy. This Review describes parallels in the injury mechanisms that underlie acute kidney injury, chronic kidney disease and allograft injury, and explains how our understanding of the molecular changes that occur in epithelia in the context of kidney disease may contribute to the therapeutic targeting of specific epithelial cell phenotypes for the treatment of transplantation complications.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":null,"pages":null},"PeriodicalIF":28.6,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140603902","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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