Pub Date : 2024-08-02DOI: 10.1038/s41581-024-00875-5
Kyungho Lee, Hye Ryoun Jang, Hamid Rabb
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.
急性肾损伤（AKI）是一种常见的严重疾病，会影响原生肾脏和异体肾脏，但目前尚无特效疗法。由淋巴细胞和先天性免疫细胞驱动的复杂肾内炎症过程在 AKI 的发生和发展中起着关键作用。许多研究都侧重于预防 AKI 早期损伤。然而，大多数 AKI 患者都是在损伤已经形成后才出现的。因此，越来越多的研究集中于 AKI 后的肾脏修复机制以及预防从 AKI 发展为慢性肾病。CD4+ 和 CD8+ T 细胞、B 细胞和中性粒细胞可能参与了 AKI 的发生和发展，而调节性 T 细胞、双阴性 T 细胞和 2 型先天性淋巴细胞具有保护作用。一些免疫细胞，如巨噬细胞和自然杀伤 T 细胞，根据其亚型和/或 AKI 阶段的不同，既可产生有害作用，也可产生保护作用。免疫系统不仅参与 AKI 期间的损伤和修复过程，还在介导 AKI 引起的远处器官功能障碍方面发挥作用。有针对性地操纵免疫细胞是改善 AKI 预后的一种很有前景的治疗策略。
{"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}
Pub Date : 2024-08-01DOI: 10.1038/s41581-024-00871-9
Ryan D. McMahan, Rebecca L. Sudore
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.
{"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}
Pub Date : 2024-07-31DOI: 10.1038/s41581-024-00864-8
Monica Suet Ying Ng, Gursimran Kaur, Ross S. Francis, Carmel M. Hawley, David W. Johnson
Drug repurposing in glomerular disease can deliver opportunities for steroid-free regimens, enable personalized multi-target options for resistant or relapsing disease and enhance treatment options for understudied populations (for example, children) and in resource-limited settings. Identification of drug-repurposing candidates can be data driven, which utilizes existing data on disease pathobiology, drug features and clinical outcomes, or experimental, which involves high-throughput drug screens. Information from databases of approved drugs, clinical trials and PubMed registries suggests that at least 96 drugs on the market cover 49 targets with immunosuppressive potential that could be candidates for drug repurposing in glomerular disease. Furthermore, evidence to support drug repurposing is available for 191 immune drug target–glomerular disease pairs. Non-immunological drug repurposing includes strategies to reduce haemodynamic overload, podocyte injury and kidney fibrosis. Recommended strategies to expand drug-repurposing capacity in glomerular disease include enriching drug databases with glomeruli-specific information, enhancing the accessibility of primary clinical trial data, biomarker discovery to improve participant selection into clinical trials and improve surrogate outcomes and initiatives to reduce patent, regulatory and organizational hurdles. Drug repurposing could expand the therapeutic options available to patients with glomerular disease. Here, the authors examine different approaches to the identification of drug candidates, consider current immunosuppressive and non-immunological options and discuss strategies to maximize drug repurposing in glomerular disease.
{"title":"Drug repurposing for glomerular diseases: an underutilized resource","authors":"Monica Suet Ying Ng, Gursimran Kaur, Ross S. Francis, Carmel M. Hawley, David W. Johnson","doi":"10.1038/s41581-024-00864-8","DOIUrl":"10.1038/s41581-024-00864-8","url":null,"abstract":"Drug repurposing in glomerular disease can deliver opportunities for steroid-free regimens, enable personalized multi-target options for resistant or relapsing disease and enhance treatment options for understudied populations (for example, children) and in resource-limited settings. Identification of drug-repurposing candidates can be data driven, which utilizes existing data on disease pathobiology, drug features and clinical outcomes, or experimental, which involves high-throughput drug screens. Information from databases of approved drugs, clinical trials and PubMed registries suggests that at least 96 drugs on the market cover 49 targets with immunosuppressive potential that could be candidates for drug repurposing in glomerular disease. Furthermore, evidence to support drug repurposing is available for 191 immune drug target–glomerular disease pairs. Non-immunological drug repurposing includes strategies to reduce haemodynamic overload, podocyte injury and kidney fibrosis. Recommended strategies to expand drug-repurposing capacity in glomerular disease include enriching drug databases with glomeruli-specific information, enhancing the accessibility of primary clinical trial data, biomarker discovery to improve participant selection into clinical trials and improve surrogate outcomes and initiatives to reduce patent, regulatory and organizational hurdles. Drug repurposing could expand the therapeutic options available to patients with glomerular disease. Here, the authors examine different approaches to the identification of drug candidates, consider current immunosuppressive and non-immunological options and discuss strategies to maximize drug repurposing in glomerular disease.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"20 11","pages":"707-721"},"PeriodicalIF":28.6,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141857700","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 : 2024-07-30DOI: 10.1038/s41581-024-00873-7
Zhao Cui, Ming-hui Zhao
A new study demonstrates that anti-nephrin autoantibodies are not merely markers but also actively contribute to the pathogenesis of minimal change disease and primary focal segmental glomerulosclerosis. This insight not only provides a non-invasive diagnostic alternative to kidney biopsies, but also suggests potential for novel targeted therapies.
{"title":"Anti-nephrin autoantibodies: a paradigm shift in podocytopathies","authors":"Zhao Cui, Ming-hui Zhao","doi":"10.1038/s41581-024-00873-7","DOIUrl":"10.1038/s41581-024-00873-7","url":null,"abstract":"A new study demonstrates that anti-nephrin autoantibodies are not merely markers but also actively contribute to the pathogenesis of minimal change disease and primary focal segmental glomerulosclerosis. This insight not only provides a non-invasive diagnostic alternative to kidney biopsies, but also suggests potential for novel targeted therapies.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"20 10","pages":"639-640"},"PeriodicalIF":28.6,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141856040","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 : 2024-07-29DOI: 10.1038/s41581-024-00876-4
Merlin C. Thomas, Mark E. Cooper
Glucagon-like peptide 1 receptor agonists improve glucose control, promote weight loss and reduce the risk of major cardiovascular events in people with type 2 diabetes mellitus. The FLOW study now provides unequivocal evidence of kidney protective effects with semaglutide in adults with type 2 diabetes mellitus and chronic kidney disease.
{"title":"The GLP-1 receptor agonist revolution comes to nephrology","authors":"Merlin C. Thomas, Mark E. Cooper","doi":"10.1038/s41581-024-00876-4","DOIUrl":"10.1038/s41581-024-00876-4","url":null,"abstract":"Glucagon-like peptide 1 receptor agonists improve glucose control, promote weight loss and reduce the risk of major cardiovascular events in people with type 2 diabetes mellitus. The FLOW study now provides unequivocal evidence of kidney protective effects with semaglutide in adults with type 2 diabetes mellitus and chronic kidney disease.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"20 10","pages":"637-638"},"PeriodicalIF":28.6,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141790952","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 : 2024-07-23DOI: 10.1038/s41581-024-00874-6
Ton J. Rabelink, Aiko P. J. de Vries
Targeting of CD38 has been posited as a potential therapeutic avenue for the treatment of immune-mediated conditions. A phase 2 study now reports promising safety, tolerability and intermediate endpoint of efficacy outcomes with the anti-CD38 monoclonal antibody felzartamab in kidney transplant recipients with antibody-mediated rejection.
{"title":"CD38 — a new target in renal immune disease","authors":"Ton J. Rabelink, Aiko P. J. de Vries","doi":"10.1038/s41581-024-00874-6","DOIUrl":"10.1038/s41581-024-00874-6","url":null,"abstract":"Targeting of CD38 has been posited as a potential therapeutic avenue for the treatment of immune-mediated conditions. A phase 2 study now reports promising safety, tolerability and intermediate endpoint of efficacy outcomes with the anti-CD38 monoclonal antibody felzartamab in kidney transplant recipients with antibody-mediated rejection.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"20 10","pages":"641-642"},"PeriodicalIF":28.6,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141752181","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 : 2024-07-22DOI: 10.1038/s41581-024-00869-3
András D. Tóth, Gábor Turu, László Hunyady
G protein-coupled receptors (GPCRs) regulate every aspect of kidney function by mediating the effects of various endogenous and exogenous substances. A key concept in GPCR function is biased signalling, whereby certain ligands may selectively activate specific pathways within the receptor’s signalling repertoire. For example, different agonists may induce biased signalling by stabilizing distinct active receptor conformations — a concept that is supported by advances in structural biology. However, the processes underlying functional selectivity in receptor signalling are extremely complex, involving differences in subcellular compartmentalization and signalling dynamics. Importantly, the molecular mechanisms of spatiotemporal bias, particularly its connection to ligand binding kinetics, have been detailed for GPCRs critical to kidney function, such as the AT1 angiotensin receptor (AT1R), V2 vasopressin receptor (V2R) and the parathyroid hormone 1 receptor (PTH1R). This expanding insight into the multifaceted nature of biased signalling paves the way for innovative strategies for targeting GPCR functions; the development of novel biased agonists may represent advanced pharmacotherapeutic approaches to the treatment of kidney diseases and related systemic conditions, such as hypertension, diabetes and heart failure. G protein-coupled receptors (GPCRs) elicit cellular responses to an array of stimuli to regulate the function of virtually all organs. The diverse functions of GPCRs are determined by their expression profiles and their ability to adopt different active and inactive conformations, resulting in functional selectivity or biased signalling. This Review describes the mechanisms and consequences of biased GPCR signalling with a focus on GPCRs of relevance to the kidney.
{"title":"Functional consequences of spatial, temporal and ligand bias of G protein-coupled receptors","authors":"András D. Tóth, Gábor Turu, László Hunyady","doi":"10.1038/s41581-024-00869-3","DOIUrl":"10.1038/s41581-024-00869-3","url":null,"abstract":"G protein-coupled receptors (GPCRs) regulate every aspect of kidney function by mediating the effects of various endogenous and exogenous substances. A key concept in GPCR function is biased signalling, whereby certain ligands may selectively activate specific pathways within the receptor’s signalling repertoire. For example, different agonists may induce biased signalling by stabilizing distinct active receptor conformations — a concept that is supported by advances in structural biology. However, the processes underlying functional selectivity in receptor signalling are extremely complex, involving differences in subcellular compartmentalization and signalling dynamics. Importantly, the molecular mechanisms of spatiotemporal bias, particularly its connection to ligand binding kinetics, have been detailed for GPCRs critical to kidney function, such as the AT1 angiotensin receptor (AT1R), V2 vasopressin receptor (V2R) and the parathyroid hormone 1 receptor (PTH1R). This expanding insight into the multifaceted nature of biased signalling paves the way for innovative strategies for targeting GPCR functions; the development of novel biased agonists may represent advanced pharmacotherapeutic approaches to the treatment of kidney diseases and related systemic conditions, such as hypertension, diabetes and heart failure. G protein-coupled receptors (GPCRs) elicit cellular responses to an array of stimuli to regulate the function of virtually all organs. The diverse functions of GPCRs are determined by their expression profiles and their ability to adopt different active and inactive conformations, resulting in functional selectivity or biased signalling. This Review describes the mechanisms and consequences of biased GPCR signalling with a focus on GPCRs of relevance to the kidney.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"20 11","pages":"722-741"},"PeriodicalIF":28.6,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141736914","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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