Kidney international最新文献

{"title":"A health economic evaluation of the multinational, randomized controlled CONVINCE trial - cost-utility of high-dose online hemodiafiltration compared to high-flux hemodialysis.","authors":"Aniek E.M. Schouten M.Sc., Felix Fischer Ph.D., Peter J. Blankestijn M.D., Robin W.M. Vernooij Ph.D., Carinna Hockham M.D., Giovanni F.M. Strippoli M.D., Bernard Canaud M.D., Jörgen Hegbrant M.D., Claudia Barth M.D., Krister Cromm M.Sc., Andrew Davenport M.D., Kathrin I. Fischer Ph.D., Matthias Rose M.D., Mariëtta Török M.D., Mark Woodward Ph.D., Michiel L. Bots M.D., G. Ardine de Wit Ph.D., Geert W.J. Frederix Ph.D., Miriam P. van der Meulen Ph.D., Convince Scientific Committee, Michiel Bots, Claudia Barth, Peter Blankestijn, Bernard Canaud, Krister Cromm, Andrew Davenport, Kathrin Fischer, Jörgen Hegbrant, Matthias Rose, Giovanni Strippoli, Mariëtta Török, Mark Woodward","doi":"10.1016/j.kint.2024.12.018","DOIUrl":"https://doi.org/10.1016/j.kint.2024.12.018","url":null,"abstract":"High-flux hemodialysis (HD) and high-dose hemodiafiltration (HDF) are established treatments for patients with kidney failure. Since HDF has been associated with improved survival rates compared to HD, we evaluated the cost-effectiveness of HDF compared to HD. Cost–utility analyses were performed from a societal perspective alongside the multinational randomized controlled CONVINCE trial. A Markov cohort model was used to extrapolate results to a lifetime time horizon. Costs of dialysis sessions were based on published data, with two scenarios reflecting different estimates for costs of dialysis staff. Other healthcare resource use, productivity losses and quality of life were collected in the electronic case report form or by country-adapted, self-reported questionnaires. Scenario and probabilistic sensitivity analyses were performed. In the two-year trial-based analysis, HDF was associated with higher quality-adjusted life years (QALYs) and higher costs, with incremental costs per QALY (ICER) of €31,898 and €37,344, depending on dialysis staff costs. The lifetime Markov cohort model resulted in ICERs of €27,068 and €36,751. Compared to HD, HDF resulted in an additional year in perfect health at increased costs. Sensitivity analyses of the lifetime analyses showed the probability of cost-effectiveness was more than 90% at willingness-to-pay threshold of €50,000/QALY. The ICER was €13,231 when excluding all costs in additional life years. The probability of cost-effectiveness was mainly driven by costs due to additional dialysis sessions in life years gained, and not due to additional costs per dialysis session. As costs may differ between countries and centers, we recommend translating our results to local settings.","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":"50 1","pages":""},"PeriodicalIF":19.6,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143020091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Repurposing mitochondria-targeted therapeutics for kidney diseases.","authors":"Austin D Thompson, Paul Victor S, Natalie E Scholpa, Rick G Schnellmann","doi":"10.1016/j.kint.2024.12.020","DOIUrl":"10.1016/j.kint.2024.12.020","url":null,"abstract":"<p><p>The kidney is one of the most metabolically demanding organs in the human body and requires a large amount of energy, in the form of adenosine triphosphate (ATP), to perform and maintain normal renal functions. To meet this energy demand, proximal tubule cells within the nephron segments of the renal cortex are mitochondrially dense with high oxygen consumption rates. Mitochondria are complex organelles involved in diverse cellular and molecular functions, including the production of ATP, calcium homeostasis, and phospholipid regulation. Mitochondrial dysfunction is critical in the onset and progression of kidney disease. Dysfunctional renal mitochondria have been linked with alterations in redox homeostasis, impaired bioenergetics, oxidative stress, and inflammation, all of which result in renal cell injury and death, as well as fibrotic accumulation in kidney injury and disease. As such, interest in the development and/or repurposing of mitochondria-targeted therapeutics for the potential treatment of kidney diseases has recently surged. Although novel therapeutics and promising new drug targets have been identified, drug repurposing for kidney diseases offers numerous advantages over traditional drug discovery initiatives, including reduced cost, time of therapeutic development, and preclinical testing, in addition to known pharmacokinetics/pharmacodynamics and safety profiles. Here, we provide an overview of mitochondrial dysfunction in the context of kidney injury and disease and shed light on promising mitochondria-targeted therapeutic agents that display repurposing potential for the restoration of renal function and/or acceleration of renal recovery.</p>","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":" ","pages":""},"PeriodicalIF":14.8,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143039244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The membrane attack complex drives thrombotic microangiopathy in complement mediated atypical hemolytic uremic syndrome.","authors":"Kate Smith-Jackson, Patrick Walsh, Wioleta M Zelek, Thomas Hoyler, Marianne M Martinic, Gemma Thompson, Beth G Gibson, Chloe Connelly, Isabel Y Pappworth, Mark J Murphy, David Kavanagh, Kevin J Marchbank","doi":"10.1016/j.kint.2024.12.016","DOIUrl":"10.1016/j.kint.2024.12.016","url":null,"abstract":"<p><p>Introduction of complement (C) inhibition into clinical practice has revolutionized the treatment of patients with complement-mediated atypical hemolytic syndrome (aHUS). Our C3^D1115N mouse model, engineered around a gain of function point mutation in C3, is associated with complement mediated aHUS in man, allowing us to study the clinical disease in a preclinical model. Backcrossing our model onto C7 deficient and C5aR1 deficient mice enabled further determination of the roles of the C5a-C5aR1 axis and C5b-9 (the membrane attack complex) on kidney disease. C7 deficiency completely abolished both clinical and histological evidence of disease. Removing C5aR1 (CD88) attenuated the risk of developing clinical disease, but mice still developed thrombotic microangiopathy. Therapeutic inhibition strengthened our genetic findings showing both anti-C7 therapy and an oral C5aR1 antagonist, when used before evidence of significant kidney injury, prevented mice from succumbing to disease. However, there was ongoing histological disease within mice treated with the C5aR1 antagonist. Our data suggest that both C5aR1 and C7 play a role in the development of the conditions required for thrombotic microangiopathy of the kidney. While disrupting the C5a-C5aR1 axis is beneficial, our genetic and therapeutic studies showed that thrombotic microangiopathy of the kidney can still develop and ultimately our data confirm that the membrane attack complex is required to develop thrombotic microangiopathy of the kidney. Overall, our study shows that in addition to requiring alternative pathway dysregulation, local generation of membrane attack complex within the kidney is also critical to drive disease pathology in complement-mediated aHUS.</p>","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":" ","pages":""},"PeriodicalIF":14.8,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143029063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of sex and gender in acute kidney injury-consensus statements from the 33rd Acute Disease Quality Initiative.","authors":"Danielle E Soranno, Linda Awdishu, Sean M Bagshaw, David Basile, Samira Bell, Azra Bihorac, Joseph Bonventre, Alessandra Brendolan, Rolando Claure-Del Granado, David Collister, Lisa M Curtis, Kristin Dolan, Dana Y Fuhrman, Zahraa Habeeb, Michael P Hutchens, Kianoush B Kashani, Nuttha Lumlertgul, Mignon McCulloch, Shina Menon, Amira Mohamed, Neesh Pannu, Karen Reue, Claudio Ronco, Manisha Sahay, Emily See, Michael Zappitelli, Ravindra Mehta, Marlies Ostermann","doi":"10.1016/j.kint.2025.01.008","DOIUrl":"10.1016/j.kint.2025.01.008","url":null,"abstract":"<p><p>Sex differences exist in acute kidney injury (AKI), and the role that sex and gender play along the AKI care continuum remains unclear. The 33rd Acute Disease Quality Initiative meeting evaluated available data on the role of sex and gender in AKI and identified knowledge gaps. Data from experimental models, pathophysiology, epidemiology, clinical care, gender, social determinants of health, education, and advocacy were reviewed. Recommendations include incorporating sex and gender into research along the bench-to-bedside spectrum; analyzing sex-stratified results; evaluating the effects of sex chromosomes, hormones, and gender on outcomes; considering fluctuations of hormone levels; studying the impact gender may have on access to care; and developing educational tools to inform patients, providers, and stakeholders. This meeting report summarizes what is known about sex and gender along the AKI care continuum and proposes an agenda for translational discovery to elucidate the role of sex and gender in AKI across the lifespan.</p>","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":" ","pages":""},"PeriodicalIF":14.8,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143029064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engineered antigen-specific T regulatory cells suppress autoreactivity to the anti-glomerular basement membrane disease antigen.","authors":"Peter J Eggenhuizen, Boaz H Ng, Cecilia Lo, Janet Chang, Sarah L Snelgrove, Rachel M Y Cheong, Chanjuan Shen, Steven Lim, Yong Zhong, Poh-Yi Gan, Joshua D Ooi","doi":"10.1016/j.kint.2025.01.005","DOIUrl":"10.1016/j.kint.2025.01.005","url":null,"abstract":"<p><p>Anti-glomerular basement membrane (anti-GBM) disease is accompanied by insufficient antigen-specific regulatory T cells (Tregs) and clonally expanded antigen-specific conventional T cells. In particular, this applied to the immunodominant T cell autoepitope of type IV collagen, α3(IV)NC1_135-145, presented by human leukocyte antigen-DRB1∗1501. Here, we investigated whether Tregs engineered to express GBM-T cell receptors (TCR) specific for α3(IV)NC1_135-145 better suppress autoimmunity. The GBM-TCR Treg cell product exhibited a phenotypically stable Treg phenotype, produced α3(IV)NC1_135-145-specific functional responses, and were superior suppressors of autoreactive conventional T cells and bystander conventional T cells compared to polyclonal Tregs or irrelevant TCR-transduced Tregs. We also found that GBM-TCR Tregs modulate other immune cells like dendritic cells and B cells to a more tolerogenic phenotype. Importantly, our findings support the development of GBM-TCR Tregs as a promising cell-based therapy for anti-GBM disease.</p>","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":" ","pages":""},"PeriodicalIF":14.8,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143023799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dynamic single cell transcriptomics defines kidney FGF23/KL bioactivity and novel segment-specific inflammatory targets.","authors":"Rafiou Agoro, Jered Myslinski, Yamil G Marambio, Danielle Janosevic, Kayleigh N Jennings, Sheng Liu, Lainey M Hibbard, Fang Fang, Pu Ni, Megan L Noonan, Emmanuel Solis, Xiaona Chu, Yue Wang, Pierre C Dagher, Yunlong Liu, Jun Wan, Takashi Hato, Kenneth E White","doi":"10.1016/j.kint.2024.12.014","DOIUrl":"10.1016/j.kint.2024.12.014","url":null,"abstract":"<p><p>Fibroblast growth factor 23 (FGF23) via its coreceptor αKlotho (KL) provides critical control of phosphate metabolism, which is altered in both rare and very common syndromes. However, the spatial-temporal mechanisms dictating kidney FGF23 functions remain poorly understood. Thus, developing approaches to modify specific FGF23-dictated pathways has proven problematic. Herein, wild type mice were injected with rFGF23 for one, four and 12h and kidney FGF23 bioactivity was determined at single cell resolution. Computational analysis identified distinct epithelial, endothelial, stromal, and immune cell clusters, with differential expressional analysis uniquely tracking FGF23 bioactivity at each time point. FGF23 actions were sex independent but critically relied upon constitutive KL expression mapped within proximal tubule (segments S1-S3) and distal convoluted tub/connecting tubule cell sub-populations. Temporal KL-dependent FGF23 responses drove unique and transient cellular identities, including genes in key MAPK-signaling and vitamin D-metabolic pathways via early- (transcription factor AP-1-related) and late-phase (initiation factor EIF2 signaling) transcriptional regulons. Combining ATACseq/RNAseq data from a cell line stably expressing KL with the in vivo scRNAseq pinpointed genomic accessibility changes in MAPK-dependent genes, including the identification of FGF23-dependent early growth factor-1 distal enhancers. Finally, we identified unexpected crosstalk between FGF23-mediated MAPK signaling and pro inflammatory TNF receptor activation via transcription factor NF-κB, which blocked FGF23 bioactivity in vitro and in vivo. Collectively, our findings have uncovered novel pathways at the single cell level that likely influence FGF23-dependent disease mechanisms.</p>","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":" ","pages":""},"PeriodicalIF":14.8,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"G-protein coupled receptor GPR124 protects against podocyte senescence and injury in diabetic kidney disease.","authors":"Yujia Li,Yiqi Duan,Qingqing Chu,Hang Lv,Jing Li,Xiangyun Guo,Yanjiao Gao,Min Liu,Wei Tang,Huili Hu,Hong Liu,Jinpeng Sun,Xiaojie Wang,Fan Yi","doi":"10.1016/j.kint.2024.12.013","DOIUrl":"https://doi.org/10.1016/j.kint.2024.12.013","url":null,"abstract":"Although emerging studies highlight the pivotal role of podocyte senescence in the pathogenesis of diabetic kidney disease (DKD) and aging-related kidney diseases, therapeutic strategies for preventing podocyte senescence are still lacking. Here, we identified a previously unrecognized role of GPR124, a novel adhesion G protein-coupled receptor, in maintaining podocyte structure and function by regulation of cellular senescence in DKD. Podocyte GPR124 was significantly reduced in db/db diabetic (a type 2 diabetic mouse model) and streptozocin-induced diabetic mice (a type 1 diabetic model), which was further confirmed in kidney biopsies from patients with DKD. The level of GPR124 in glomeruli was positively correlated with the estimated glomerular filtration rate and negatively correlated with serum creatinine levels. Podocyte-specific deficiency of GPR124 significantly aggravated podocyte injury and proteinuria in the two models of diabetic mice. Moreover, GPR124 regulated podocyte senescence in both diabetic and aged mice. Mechanistically, GPR124 directly bound with vinculin and negatively regulated focal adhesion kinase (FAK) signaling, thereby mediating podocyte senescence and function. Importantly, overexpression of GPR124 or pharmacological inhibition of FAK protected against podocyte senescence and injury under diabetic conditions. Our studies suggest that targeting GPR124 may be an innovative therapeutic strategy for patients with DKD and aging-related kidney diseases.","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":"37 1","pages":""},"PeriodicalIF":19.6,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142991718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Filtering through AAV Capsid Libraries for Effective Kidney Gene Transfer.","authors":"Aravind Asokan,Matthew H Wilson","doi":"10.1016/j.kint.2024.12.012","DOIUrl":"https://doi.org/10.1016/j.kint.2024.12.012","url":null,"abstract":"","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":"50 1","pages":""},"PeriodicalIF":19.6,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142988794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnosis and management of immune checkpoint inhibitor–associated nephrotoxicity: a position statement from the American Society of Onco-nephrology","authors":"Sandra M. Herrmann ,&nbsp;Ala Abudayyeh ,&nbsp;Shruti Gupta ,&nbsp;Prakash Gudsoorkar ,&nbsp;Nattawat Klomjit ,&nbsp;Shveta S. Motwani ,&nbsp;Sabine Karam ,&nbsp;Verônica T. Costa E Silva ,&nbsp;Sheikh B. Khalid ,&nbsp;Shuchi Anand ,&nbsp;Jaya Kala ,&nbsp;David E. Leaf ,&nbsp;Naoka Murakami ,&nbsp;Arash Rashidi ,&nbsp;Rimda Wanchoo ,&nbsp;Abhijat Kitchlu","doi":"10.1016/j.kint.2024.09.017","DOIUrl":"10.1016/j.kint.2024.09.017","url":null,"abstract":"<div><div>Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of cancer and are now the backbone of therapy for several malignancies. However, ICIs can cause a spectrum of kidney immune-related adverse events including acute kidney injury (AKI), most commonly manifesting as acute interstitial nephritis (AIN), although glomerular disease and electrolyte disturbances have also been reported. In this position statement by the American Society of Onco-nephrology (ASON), we summarize the incidence and risk factors for ICI-AKI, pathophysiological mechanisms, and clinicopathologic features of ICI-AKI. We also discuss novel diagnostic approaches and promising biomarkers for ICI-AKI. From expert panel consensus, we provide clinical practice points for the initial assessment and diagnosis of ICI-AKI, management and immunosuppressive therapy, and consideration for rechallenge with ICI following AKI episodes. In addition, we explore ICI use in special populations, such as kidney transplant recipients, and propose key areas of focus for future research and clinical investigation.</div></div>","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":"107 1","pages":"Pages 21-32"},"PeriodicalIF":14.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142503094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unlocking the potential of extracellular vesicles in nephrology: what does MISEV2023 add?","authors":"Monica Suet Ying Ng ,&nbsp;Dylan Burger ,&nbsp;Per Svenningsen ,&nbsp;Elena Martens ,&nbsp;Uta Erdbrügger ,&nbsp;Fabian Braun","doi":"10.1016/j.kint.2024.07.037","DOIUrl":"10.1016/j.kint.2024.07.037","url":null,"abstract":"<div><div>Extracellular vesicles, small membrane-bound packages secreted by virtually all cells of the body, have become a focus of interest in nephrology over the recent years. After the first characterization of their proteomic and transcriptomic content, scientific attention shifted toward their potential as biomarkers for kidney diseases both as diagnostic and monitoring tools. More recently, researchers have begun exploring whether extracellular vesicles mediate intercellular signaling inside the nephron and between the kidney and other organs throughout the body. Nevertheless, the field of extracellular vesicle research has struggled to translate major findings to the clinical context due to numerous methods to separate extracellular vesicles, yielding fractions of different sizes and varying purity, unclear terminology, and, hence, limitations concerning reproducibility. The International Society of Extracellular Vesicles, therefore, has striven to reduce these barriers by an ongoing initiative to increase rigor and standardization of extracellular vesicle research. The “Minimal Information for Studies of Extracellular Vesicles” guideline is the result of this initiative and, in its now third iteration, provides the most concise suggestions for investigating extracellular vesicles to date. This mini review illustrates the advances made in extracellular vesicle research in nephrology so far using informative examples, outlines the advances made by the former Minimal Information for Studies of Extracellular Vesicles guidelines, and shows what potential using the latest iteration holds.</div></div>","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":"107 1","pages":"Pages 44-50"},"PeriodicalIF":14.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142623198","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}