Pub Date : 2024-07-04DOI: 10.1038/s41581-024-00861-x
Paola Tasca, Bernard M. van den Berg, Ton J. Rabelink, Gangqi Wang, Bram Heijs, Cees van Kooten, Aiko P. J. de Vries, Jesper Kers
Improvement of long-term outcomes through targeted treatment is a primary concern in kidney transplant medicine. Currently, the validation of a rejection diagnosis and subsequent treatment depends on the histological assessment of allograft biopsy samples, according to the Banff classification system. However, the lack of (early) disease-specific tissue markers hinders accurate diagnosis and thus timely intervention. This challenge mainly results from an incomplete understanding of the pathophysiological processes underlying late allograft failure. Integration of large-scale multimodal approaches for investigating allograft biopsy samples might offer new insights into this pathophysiology, which are necessary for the identification of novel therapeutic targets and the development of tailored immunotherapeutic interventions. Several omics technologies — including transcriptomic, proteomic, lipidomic and metabolomic tools (and multimodal data analysis strategies) — can be applied to allograft biopsy investigation. However, despite their successful application in research settings and their potential clinical value, several barriers limit the broad implementation of many of these tools into clinical practice. Among spatial-omics technologies, mass spectrometry imaging, which is under-represented in the transplant field, has the potential to enable multi-omics investigations that might expand the insights gained with current clinical analysis technologies. Technological advances continue to enhance the clinical value of kidney biopsies. Here, the authors consider the potential of using spatial-omics in transplantation, including the use of mass spectrometry imaging, as graft monitoring and diagnostic tools, to improve patient management and outcomes.
{"title":"Application of spatial-omics to the classification of kidney biopsy samples in transplantation","authors":"Paola Tasca, Bernard M. van den Berg, Ton J. Rabelink, Gangqi Wang, Bram Heijs, Cees van Kooten, Aiko P. J. de Vries, Jesper Kers","doi":"10.1038/s41581-024-00861-x","DOIUrl":"10.1038/s41581-024-00861-x","url":null,"abstract":"Improvement of long-term outcomes through targeted treatment is a primary concern in kidney transplant medicine. Currently, the validation of a rejection diagnosis and subsequent treatment depends on the histological assessment of allograft biopsy samples, according to the Banff classification system. However, the lack of (early) disease-specific tissue markers hinders accurate diagnosis and thus timely intervention. This challenge mainly results from an incomplete understanding of the pathophysiological processes underlying late allograft failure. Integration of large-scale multimodal approaches for investigating allograft biopsy samples might offer new insights into this pathophysiology, which are necessary for the identification of novel therapeutic targets and the development of tailored immunotherapeutic interventions. Several omics technologies — including transcriptomic, proteomic, lipidomic and metabolomic tools (and multimodal data analysis strategies) — can be applied to allograft biopsy investigation. However, despite their successful application in research settings and their potential clinical value, several barriers limit the broad implementation of many of these tools into clinical practice. Among spatial-omics technologies, mass spectrometry imaging, which is under-represented in the transplant field, has the potential to enable multi-omics investigations that might expand the insights gained with current clinical analysis technologies. Technological advances continue to enhance the clinical value of kidney biopsies. Here, the authors consider the potential of using spatial-omics in transplantation, including the use of mass spectrometry imaging, as graft monitoring and diagnostic tools, to improve patient management and outcomes.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":null,"pages":null},"PeriodicalIF":28.6,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141521722","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 : 2024-07-03DOI: 10.1038/s41581-024-00850-0
Anaïs Beyze, Christian Larroque, Moglie Le Quintrec
Immunoglobulin glycosylation is a pivotal mechanism that drives the diversification of antibody functions. The composition of the IgG glycome is influenced by environmental factors, genetic traits and inflammatory contexts. Differential IgG glycosylation has been shown to intricately modulate IgG effector functions and has a role in the initiation and progression of various diseases. Analysis of IgG glycosylation is therefore a promising tool for predicting disease severity. Several autoimmune and alloimmune disorders, including critical and potentially life-threatening conditions such as systemic lupus erythematosus, anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis and antibody-mediated kidney graft rejection, are driven by immunoglobulin. In certain IgG-driven kidney diseases, including primary membranous nephropathy, IgA nephropathy and lupus nephritis, particular glycome characteristics can enhance in situ complement activation and the recruitment of innate immune cells, resulting in more severe kidney damage. Hypofucosylation, hypogalactosylation and hyposialylation are the most common IgG glycosylation traits identified in these diseases. Modulating IgG glycosylation could therefore be a promising therapeutic strategy for regulating the immune mechanisms that underlie IgG-driven kidney diseases and potentially reduce the burden of immunosuppressive drugs in affected patients. Here, the authors review the impact of IgG glycosylation in kidney diseases, particularly autoimmune diseases and antibody-mediated rejection. They also discuss the signalling pathways that govern antibody glycosylation, the impact of glycosylation on antibody functions and implications for therapy.
{"title":"The role of antibody glycosylation in autoimmune and alloimmune kidney diseases","authors":"Anaïs Beyze, Christian Larroque, Moglie Le Quintrec","doi":"10.1038/s41581-024-00850-0","DOIUrl":"10.1038/s41581-024-00850-0","url":null,"abstract":"Immunoglobulin glycosylation is a pivotal mechanism that drives the diversification of antibody functions. The composition of the IgG glycome is influenced by environmental factors, genetic traits and inflammatory contexts. Differential IgG glycosylation has been shown to intricately modulate IgG effector functions and has a role in the initiation and progression of various diseases. Analysis of IgG glycosylation is therefore a promising tool for predicting disease severity. Several autoimmune and alloimmune disorders, including critical and potentially life-threatening conditions such as systemic lupus erythematosus, anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis and antibody-mediated kidney graft rejection, are driven by immunoglobulin. In certain IgG-driven kidney diseases, including primary membranous nephropathy, IgA nephropathy and lupus nephritis, particular glycome characteristics can enhance in situ complement activation and the recruitment of innate immune cells, resulting in more severe kidney damage. Hypofucosylation, hypogalactosylation and hyposialylation are the most common IgG glycosylation traits identified in these diseases. Modulating IgG glycosylation could therefore be a promising therapeutic strategy for regulating the immune mechanisms that underlie IgG-driven kidney diseases and potentially reduce the burden of immunosuppressive drugs in affected patients. Here, the authors review the impact of IgG glycosylation in kidney diseases, particularly autoimmune diseases and antibody-mediated rejection. They also discuss the signalling pathways that govern antibody glycosylation, the impact of glycosylation on antibody functions and implications for therapy.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":null,"pages":null},"PeriodicalIF":28.6,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141498536","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 : 2024-07-02DOI: 10.1038/s41581-024-00867-5
Susan J. Allison
{"title":"Regulation of kidney fibrosis by ILC3s via a gut–kidney axis","authors":"Susan J. Allison","doi":"10.1038/s41581-024-00867-5","DOIUrl":"10.1038/s41581-024-00867-5","url":null,"abstract":"","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":null,"pages":null},"PeriodicalIF":28.6,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141492738","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 : 2024-07-02DOI: 10.1038/s41581-024-00866-6
Ellen F. Carney
{"title":"Avenciguat reduces albuminuria in patients with chronic kidney disease","authors":"Ellen F. Carney","doi":"10.1038/s41581-024-00866-6","DOIUrl":"10.1038/s41581-024-00866-6","url":null,"abstract":"","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":null,"pages":null},"PeriodicalIF":28.6,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141492737","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 : 2024-07-02DOI: 10.1038/s41581-024-00865-7
Ellen F. Carney
{"title":"A pre-specified analysis of the SELECT trial suggests a kidney benefit of semaglutide in patients without diabetes","authors":"Ellen F. Carney","doi":"10.1038/s41581-024-00865-7","DOIUrl":"10.1038/s41581-024-00865-7","url":null,"abstract":"","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":null,"pages":null},"PeriodicalIF":28.6,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141492736","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 : 2024-06-19DOI: 10.1038/s41581-024-00862-w
Olivier Thaunat
Graft rejection is traditionally attributed to adaptive immune cells that recognize donor-specific alloantigens, with innate immunity having a secondary role. The finding that recipient natural killer cells are activated by the inability of graft endothelial cells to provide HLA-I-mediated inhibitory signals challenges this dogma and introduces the concept of innate rejection.
{"title":"Natural killer cell-mediated innate microvascular rejection","authors":"Olivier Thaunat","doi":"10.1038/s41581-024-00862-w","DOIUrl":"10.1038/s41581-024-00862-w","url":null,"abstract":"Graft rejection is traditionally attributed to adaptive immune cells that recognize donor-specific alloantigens, with innate immunity having a secondary role. The finding that recipient natural killer cells are activated by the inability of graft endothelial cells to provide HLA-I-mediated inhibitory signals challenges this dogma and introduces the concept of innate rejection.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":null,"pages":null},"PeriodicalIF":28.6,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141425227","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 : 2024-06-18DOI: 10.1038/s41581-024-00851-z
Vidya A. Fleetwood, Krista L. Lentine
Kidneys from older donors might improve the quality of life and survival of patients with kidney failure, yet these organs are often underutilized. Re-framing discussions of organ acceptance from older donors and its benefits over dialysis, especially for older patients and those who cannot tolerate prolonged waiting for transplantation, is urgently needed.
{"title":"Unlocking the benefits of transplantation with kidneys from older donors","authors":"Vidya A. Fleetwood, Krista L. Lentine","doi":"10.1038/s41581-024-00851-z","DOIUrl":"10.1038/s41581-024-00851-z","url":null,"abstract":"Kidneys from older donors might improve the quality of life and survival of patients with kidney failure, yet these organs are often underutilized. Re-framing discussions of organ acceptance from older donors and its benefits over dialysis, especially for older patients and those who cannot tolerate prolonged waiting for transplantation, is urgently needed.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":null,"pages":null},"PeriodicalIF":28.6,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141419907","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 : 2024-06-18DOI: 10.1038/s41581-024-00857-7
Katarina Zeder, Edward D. Siew, Gabor Kovacs, Evan L. Brittain, Bradley A. Maron
Pulmonary hypertension (PH) is common in patients with chronic kidney disease (CKD) or kidney failure, with an estimated prevalence of up to 78% in those referred for right-heart catheterization. PH is independently associated with adverse outcomes in CKD, raising the possibility that early detection and appropriate management of PH might improve outcomes in at-risk patients. Among patients with PH, the prevalence of CKD stages 3 and 4 is estimated to be as high as 36%, and CKD is also independently associated with adverse outcomes. However, the complex, heterogenous pathophysiology and clinical profile of CKD–PH requires further characterization. CKD is often associated with elevated left ventricular filling pressure and volume overload, which presumably leads to pulmonary vascular stiffening and post-capillary PH. By contrast, a distinct subgroup of patients at high risk is characterized by elevated pulmonary vascular resistance and right ventricular dysfunction in the absence of pulmonary venous hypertension, which may represent a right-sided cardiorenal syndrome defined in principle by hypervolaemia, salt avidity, low cardiac output and normal left ventricular function. Current understanding of CKD–PH is limited, despite its potentially important ramifications for clinical decision making. In particular, whether PH should be considered when determining the suitability and timing of kidney replacement therapy or kidney transplantation is unclear. More research is urgently needed to address these knowledge gaps and improve the outcomes of patients with or at risk of CKD–PH. In this Review, the authors discuss potential pathophenotypes of coexisting chronic kidney disease and pulmonary hypertension, discuss the principles of clinical management of patients with chronic kidney disease or kidney failure and pulmonary hypertension, and outline key areas for further research.
{"title":"Pulmonary hypertension and chronic kidney disease: prevalence, pathophysiology and outcomes","authors":"Katarina Zeder, Edward D. Siew, Gabor Kovacs, Evan L. Brittain, Bradley A. Maron","doi":"10.1038/s41581-024-00857-7","DOIUrl":"10.1038/s41581-024-00857-7","url":null,"abstract":"Pulmonary hypertension (PH) is common in patients with chronic kidney disease (CKD) or kidney failure, with an estimated prevalence of up to 78% in those referred for right-heart catheterization. PH is independently associated with adverse outcomes in CKD, raising the possibility that early detection and appropriate management of PH might improve outcomes in at-risk patients. Among patients with PH, the prevalence of CKD stages 3 and 4 is estimated to be as high as 36%, and CKD is also independently associated with adverse outcomes. However, the complex, heterogenous pathophysiology and clinical profile of CKD–PH requires further characterization. CKD is often associated with elevated left ventricular filling pressure and volume overload, which presumably leads to pulmonary vascular stiffening and post-capillary PH. By contrast, a distinct subgroup of patients at high risk is characterized by elevated pulmonary vascular resistance and right ventricular dysfunction in the absence of pulmonary venous hypertension, which may represent a right-sided cardiorenal syndrome defined in principle by hypervolaemia, salt avidity, low cardiac output and normal left ventricular function. Current understanding of CKD–PH is limited, despite its potentially important ramifications for clinical decision making. In particular, whether PH should be considered when determining the suitability and timing of kidney replacement therapy or kidney transplantation is unclear. More research is urgently needed to address these knowledge gaps and improve the outcomes of patients with or at risk of CKD–PH. In this Review, the authors discuss potential pathophenotypes of coexisting chronic kidney disease and pulmonary hypertension, discuss the principles of clinical management of patients with chronic kidney disease or kidney failure and pulmonary hypertension, and outline key areas for further research.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":null,"pages":null},"PeriodicalIF":28.6,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141419906","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 : 2024-06-17DOI: 10.1038/s41581-024-00860-y
Yasumichi Arai, Motoko Yanagita
Centenarians — who are a putative model of healthy longevity — often have a low risk of cardiovascular disease, despite an age-associated decline in kidney function. An understanding of the molecular and cellular underpinnings of health kidney ageing in centenarians may provide clues for the prevention or alleviation of the burden of kidney disease in older populations.
{"title":"Healthy ageing and the kidney — lessons from centenarians","authors":"Yasumichi Arai, Motoko Yanagita","doi":"10.1038/s41581-024-00860-y","DOIUrl":"10.1038/s41581-024-00860-y","url":null,"abstract":"Centenarians — who are a putative model of healthy longevity — often have a low risk of cardiovascular disease, despite an age-associated decline in kidney function. An understanding of the molecular and cellular underpinnings of health kidney ageing in centenarians may provide clues for the prevention or alleviation of the burden of kidney disease in older populations.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":null,"pages":null},"PeriodicalIF":28.6,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141333552","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 : 2024-06-12DOI: 10.1038/s41581-024-00849-7
Paula Unger Avila, Tsimafei Padvitski, Ana Carolina Leote, He Chen, Julio Saez-Rodriguez, Martin Kann, Andreas Beyer
The precise control of gene expression is required for the maintenance of cellular homeostasis and proper cellular function, and the declining control of gene expression with age is considered a major contributor to age-associated changes in cellular physiology and disease. The coordination of gene expression can be represented through models of the molecular interactions that govern gene expression levels, so-called gene regulatory networks. Gene regulatory networks can represent interactions that occur through signal transduction, those that involve regulatory transcription factors, or statistical models of gene–gene relationships based on the premise that certain sets of genes tend to be coexpressed across a range of conditions and cell types. Advances in experimental and computational technologies have enabled the inference of these networks on an unprecedented scale and at unprecedented precision. Here, we delineate different types of gene regulatory networks and their cell-biological interpretation. We describe methods for inferring such networks from large-scale, multi-omics datasets and present applications that have aided our understanding of cellular ageing and disease mechanisms. Perturbations in the regulation of gene expression can contribute to disease- and ageing-associated changes in cell physiology. This review describes how the coordination of gene expression within and between cells can be represented through models of the molecular interactions that govern gene expression levels, and how such models can be used to understand age-associated changes in cell physiology.
{"title":"Gene regulatory networks in disease and ageing","authors":"Paula Unger Avila, Tsimafei Padvitski, Ana Carolina Leote, He Chen, Julio Saez-Rodriguez, Martin Kann, Andreas Beyer","doi":"10.1038/s41581-024-00849-7","DOIUrl":"10.1038/s41581-024-00849-7","url":null,"abstract":"The precise control of gene expression is required for the maintenance of cellular homeostasis and proper cellular function, and the declining control of gene expression with age is considered a major contributor to age-associated changes in cellular physiology and disease. The coordination of gene expression can be represented through models of the molecular interactions that govern gene expression levels, so-called gene regulatory networks. Gene regulatory networks can represent interactions that occur through signal transduction, those that involve regulatory transcription factors, or statistical models of gene–gene relationships based on the premise that certain sets of genes tend to be coexpressed across a range of conditions and cell types. Advances in experimental and computational technologies have enabled the inference of these networks on an unprecedented scale and at unprecedented precision. Here, we delineate different types of gene regulatory networks and their cell-biological interpretation. We describe methods for inferring such networks from large-scale, multi-omics datasets and present applications that have aided our understanding of cellular ageing and disease mechanisms. Perturbations in the regulation of gene expression can contribute to disease- and ageing-associated changes in cell physiology. This review describes how the coordination of gene expression within and between cells can be represented through models of the molecular interactions that govern gene expression levels, and how such models can be used to understand age-associated changes in cell physiology.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":null,"pages":null},"PeriodicalIF":28.6,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141308941","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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