Pub Date : 2024-09-18DOI: 10.1016/j.kint.2024.09.005
Nicolette C Bishop
{"title":"Unpicking the multi-omic response to endurance training: relevance for exercise benefits in chronic kidney disease.","authors":"Nicolette C Bishop","doi":"10.1016/j.kint.2024.09.005","DOIUrl":"https://doi.org/10.1016/j.kint.2024.09.005","url":null,"abstract":"","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":"23 1","pages":""},"PeriodicalIF":19.6,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142275251","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 : 2024-09-18DOI: 10.1016/j.kint.2024.07.019
Marcelle Tuttle , Andrew S. Levey
Plasma or urinary clearance of exogenous filtration markers is required for assessment of measured glomerular filtration rate. Although multiple methods are available, none is widely used because of their complexity, each has measurement error, and standardization is limited. Recently, a study validated the plasma clearance of a new exogenous filtration marker, relmapirazin, which can be detected by its transdermal fluorescence, potentially simplifying the procedure and increasing access to measured glomerular filtration rate.
{"title":"Relmapirazin, a new exogenous filtration marker, and more widespread use of measured GFR","authors":"Marcelle Tuttle , Andrew S. Levey","doi":"10.1016/j.kint.2024.07.019","DOIUrl":"10.1016/j.kint.2024.07.019","url":null,"abstract":"<div><p>Plasma or urinary clearance of exogenous filtration markers is required for assessment of measured glomerular filtration rate. Although multiple methods are available, none is widely used because of their complexity, each has measurement error, and standardization is limited. Recently, a study validated the plasma clearance of a new exogenous filtration marker, relmapirazin, which can be detected by its transdermal fluorescence, potentially simplifying the procedure and increasing access to measured glomerular filtration rate.</p></div>","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":"106 4","pages":"Pages 562-565"},"PeriodicalIF":14.8,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0085253824005416/pdfft?md5=e1b2629eafc80d55260a35b7fed83894&pid=1-s2.0-S0085253824005416-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142274731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-17DOI: 10.1016/j.kint.2024.08.030
Tilman B Drueke,François Alhenc-Gelas
{"title":"A new mechanism in adrenal control of aldosterone secretion involving the macrophage and VEGF.","authors":"Tilman B Drueke,François Alhenc-Gelas","doi":"10.1016/j.kint.2024.08.030","DOIUrl":"https://doi.org/10.1016/j.kint.2024.08.030","url":null,"abstract":"","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":"213 1","pages":""},"PeriodicalIF":19.6,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142273496","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 : 2024-09-12DOI: 10.1016/j.kint.2024.07.035
Krishna A. Agarwal , Ogechi M. Adingwupu , Hocine Tighiouart , Shiyuan Miao , Marc Froissart , Michael Mauer , Wei Yang , Vicente Torres , Martin de Borst , Goran Klintmalm , Emilio D. Poggio , Peter Rossing , Ruben Velez , Anders Grubb , Andrew D. Rule , Kamran Shaffi , Ashtar Chami , Andrew S. Levey , Lesley A. Inker
{"title":"Estimating glomerular filtration rate in kidney transplant recipients: considerations for selecting equations","authors":"Krishna A. Agarwal , Ogechi M. Adingwupu , Hocine Tighiouart , Shiyuan Miao , Marc Froissart , Michael Mauer , Wei Yang , Vicente Torres , Martin de Borst , Goran Klintmalm , Emilio D. Poggio , Peter Rossing , Ruben Velez , Anders Grubb , Andrew D. Rule , Kamran Shaffi , Ashtar Chami , Andrew S. Levey , Lesley A. Inker","doi":"10.1016/j.kint.2024.07.035","DOIUrl":"10.1016/j.kint.2024.07.035","url":null,"abstract":"","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":"106 5","pages":"Pages 991-995"},"PeriodicalIF":14.8,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142174732","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 : 2024-09-07DOI: 10.1016/j.kint.2024.08.012
Chee Kay Cheung , Jonathan Barratt , Richard Lafayette , Adrian Liew , Yusuke Suzuki , Vladimír Tesař , Hernán Trimarchi , Muh Geot Wong , Hong Zhang , Dana V. Rizk
A proliferation-inducing ligand (APRIL) is a key member of the tumor necrosis factor superfamily of cytokines and plays a central role in B-cell survival, proliferation, and Ig class switching. Recently, there has been increasing interest in the role of APRIL and the related cytokine B-cell activating factor in several glomerular diseases, because of their importance in the above processes. The therapeutic inhibition of APRIL represents a potentially attractive immunomodulatory approach that may abrogate deleterious host immune responses in autoimmune diseases while leaving other important functions of humoral immunity intact, such as memory B-cell function and responses to vaccination, in contrast to B-cell–depleting strategies. In this review, we describe the physiological roles of APRIL in B-cell development and their relevance to glomerular diseases, and outline emerging clinical trial data studying APRIL inhibition, with a focus on IgA nephropathy where the clinical development of APRIL inhibitors is in its most advanced stage.
增殖诱导配体（APRIL）是肿瘤坏死因子（TNF）超家族细胞因子的一个重要成员，在 B 细胞存活、增殖和免疫球蛋白类别转换中起着核心作用。最近，由于 APRIL 和相关细胞因子 B 细胞活化因子（BAFF）在上述过程中的重要作用，人们越来越关注它们在几种肾小球疾病中的作用。治疗性抑制 APRIL 代表了一种具有潜在吸引力的免疫调节方法，它可以消除自身免疫性疾病中有害的宿主免疫反应，同时保持体液免疫的其他重要功能完好无损，如记忆 B 细胞功能和疫苗接种反应，与 B 细胞耗竭策略形成鲜明对比。在这篇综述中，我们描述了APRIL在B细胞发育中的生理作用及其与肾小球疾病的相关性，并概述了研究APRIL抑制剂的新临床试验数据，重点是IgA肾病，APRIL抑制剂的临床开发正处于最后期阶段。
{"title":"Targeting APRIL in the treatment of glomerular diseases","authors":"Chee Kay Cheung , Jonathan Barratt , Richard Lafayette , Adrian Liew , Yusuke Suzuki , Vladimír Tesař , Hernán Trimarchi , Muh Geot Wong , Hong Zhang , Dana V. Rizk","doi":"10.1016/j.kint.2024.08.012","DOIUrl":"10.1016/j.kint.2024.08.012","url":null,"abstract":"<div><div>A proliferation-inducing ligand (APRIL) is a key member of the tumor necrosis factor superfamily of cytokines and plays a central role in B-cell survival, proliferation, and Ig class switching. Recently, there has been increasing interest in the role of APRIL and the related cytokine B-cell activating factor in several glomerular diseases, because of their importance in the above processes. The therapeutic inhibition of APRIL represents a potentially attractive immunomodulatory approach that may abrogate deleterious host immune responses in autoimmune diseases while leaving other important functions of humoral immunity intact, such as memory B-cell function and responses to vaccination, in contrast to B-cell–depleting strategies. In this review, we describe the physiological roles of APRIL in B-cell development and their relevance to glomerular diseases, and outline emerging clinical trial data studying APRIL inhibition, with a focus on IgA nephropathy where the clinical development of APRIL inhibitors is in its most advanced stage.</div></div>","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":"106 5","pages":"Pages 806-818"},"PeriodicalIF":14.8,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142055925","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 : 2024-08-31DOI: 10.1016/j.kint.2024.08.023
Viknesh Selvarajah, Darren Robertson, Lars Hansen, Lutz Jermutus, Kirsten Smith, Angela Coggi, José Sánchez, Yi-Ting Chang, Hongtao Yu, Joanna Parkinson, Anis Khan, H Sophia Chung, Sonja Hess, Richard Dumas, Tabbatha Duck, Simran Jolly, Tom G Elliott, John Baker, Albert Lecube, Karl-Michael Derwahl, Russell Scott, Cristobal Morales, Carl Peters, Ronald Goldenberg, Victoria E R Parker, Hiddo J L Heerspink
Cotadutide is a glucagon-like peptide-1 (GLP-1) and glucagon receptor agonist that may improve kidney function in patients with type 2 diabetes (T2D) and chronic kidney disease (CKD). In this phase 2b study, patients with T2D and CKD (estimated glomerular filtration rate [eGFR] of 20 or more and under 90 mL/min per 1.73 m2 and urinary albumin-to-creatinine ratio [UACR] over 50 mg/g) were randomized 1:1:1:1:1 to 26 weeks' treatment with standard of care plus subcutaneous cotadutide uptitrated to 100, 300, or 600 μg, or placebo daily (double-blind), or the GLP-1 agonist semaglutide 1 mg once weekly (open-label).The co-primary endpoints were absolute and percentage change versus placebo in UACR from baseline to the end of week 14. Among 248 randomized patients, mean age 67.1 years, 19% were female, mean eGFR was 55.3 mL/min per 1.73 m2, geometric mean was UACR 205.5 mg/g (coefficient of variation 270.0), and 46.8% were receiving concomitant sodium-glucose co-transporter 2 inhibitors. Cotadutide dose-dependently reduced UACR from baseline to the end of week 14, reaching significance at 300 μg (-43.9% [95% confidence interval -54.7 to -30.6]) and 600 μg (-49.9% [-59.3 to -38.4]) versus placebo; with effects sustained at week 26. Serious adverse events were balanced across arms. Safety and tolerability of cotadutide 600 μg were comparable to semaglutide. Thus, our study shows that in patients with T2D and CKD, cotadutide significantly reduced UACR on top of standard of care with an acceptable tolerability profile, suggesting kidney protective benefits that need confirmation in a larger study.
{"title":"A randomized phase 2b trial examined the effects of the glucagon-like peptide-1 and glucagon receptor agonist cotadutide on kidney outcomes in patients with diabetic kidney disease.","authors":"Viknesh Selvarajah, Darren Robertson, Lars Hansen, Lutz Jermutus, Kirsten Smith, Angela Coggi, José Sánchez, Yi-Ting Chang, Hongtao Yu, Joanna Parkinson, Anis Khan, H Sophia Chung, Sonja Hess, Richard Dumas, Tabbatha Duck, Simran Jolly, Tom G Elliott, John Baker, Albert Lecube, Karl-Michael Derwahl, Russell Scott, Cristobal Morales, Carl Peters, Ronald Goldenberg, Victoria E R Parker, Hiddo J L Heerspink","doi":"10.1016/j.kint.2024.08.023","DOIUrl":"10.1016/j.kint.2024.08.023","url":null,"abstract":"<p><p>Cotadutide is a glucagon-like peptide-1 (GLP-1) and glucagon receptor agonist that may improve kidney function in patients with type 2 diabetes (T2D) and chronic kidney disease (CKD). In this phase 2b study, patients with T2D and CKD (estimated glomerular filtration rate [eGFR] of 20 or more and under 90 mL/min per 1.73 m<sup>2</sup> and urinary albumin-to-creatinine ratio [UACR] over 50 mg/g) were randomized 1:1:1:1:1 to 26 weeks' treatment with standard of care plus subcutaneous cotadutide uptitrated to 100, 300, or 600 μg, or placebo daily (double-blind), or the GLP-1 agonist semaglutide 1 mg once weekly (open-label).The co-primary endpoints were absolute and percentage change versus placebo in UACR from baseline to the end of week 14. Among 248 randomized patients, mean age 67.1 years, 19% were female, mean eGFR was 55.3 mL/min per 1.73 m<sup>2</sup>, geometric mean was UACR 205.5 mg/g (coefficient of variation 270.0), and 46.8% were receiving concomitant sodium-glucose co-transporter 2 inhibitors. Cotadutide dose-dependently reduced UACR from baseline to the end of week 14, reaching significance at 300 μg (-43.9% [95% confidence interval -54.7 to -30.6]) and 600 μg (-49.9% [-59.3 to -38.4]) versus placebo; with effects sustained at week 26. Serious adverse events were balanced across arms. Safety and tolerability of cotadutide 600 μg were comparable to semaglutide. Thus, our study shows that in patients with T2D and CKD, cotadutide significantly reduced UACR on top of standard of care with an acceptable tolerability profile, suggesting kidney protective benefits that need confirmation in a larger study.</p>","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":" ","pages":""},"PeriodicalIF":14.8,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142108748","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 : 2024-08-31DOI: 10.1016/j.kint.2024.07.034
Veenita Khare, Stephanie Cherqui
Chronic kidney disease is one of the leading causes of mortality worldwide because of kidney failure and the associated challenges of its treatment including dialysis and kidney transplantation. About one-third of chronic kidney disease cases are linked to inherited monogenic factors, making them suitable for potential gene therapy interventions. However, the intricate anatomical structure of the kidney poses a challenge, limiting the effectiveness of targeted gene delivery to the renal system. In this review, we explore the progress made in the field of targeted gene therapy approaches and their implications for rare genetic kidney disorders, examining preclinical studies and prospects for clinical application. In vivo gene therapy is most commonly used for kidney-targeted gene delivery and involves administering viral and nonviral vectors through various routes such as systemic, renal vein, and renal arterial injections. Small nucleic acids have also been used in preclinical and clinical studies for treating certain kidney disorders. Unexpectedly, hematopoietic stem and progenitor cells have been used as an ex vivo gene therapy vehicle for kidney gene delivery, highlighting their ability to differentiate into macrophages within the kidney, forming tunneling nanotubes that can deliver genetic material and organelles to adjacent kidney cells, even across the basement membrane to target the proximal tubular cells. As gene therapy technologies continue to advance and our understanding of kidney biology deepens, there is hope for patients with genetic kidney disorders to eventually avoid kidney transplantation.
{"title":"Targeted gene therapy for rare genetic kidney diseases.","authors":"Veenita Khare, Stephanie Cherqui","doi":"10.1016/j.kint.2024.07.034","DOIUrl":"10.1016/j.kint.2024.07.034","url":null,"abstract":"<p><p>Chronic kidney disease is one of the leading causes of mortality worldwide because of kidney failure and the associated challenges of its treatment including dialysis and kidney transplantation. About one-third of chronic kidney disease cases are linked to inherited monogenic factors, making them suitable for potential gene therapy interventions. However, the intricate anatomical structure of the kidney poses a challenge, limiting the effectiveness of targeted gene delivery to the renal system. In this review, we explore the progress made in the field of targeted gene therapy approaches and their implications for rare genetic kidney disorders, examining preclinical studies and prospects for clinical application. In vivo gene therapy is most commonly used for kidney-targeted gene delivery and involves administering viral and nonviral vectors through various routes such as systemic, renal vein, and renal arterial injections. Small nucleic acids have also been used in preclinical and clinical studies for treating certain kidney disorders. Unexpectedly, hematopoietic stem and progenitor cells have been used as an ex vivo gene therapy vehicle for kidney gene delivery, highlighting their ability to differentiate into macrophages within the kidney, forming tunneling nanotubes that can deliver genetic material and organelles to adjacent kidney cells, even across the basement membrane to target the proximal tubular cells. As gene therapy technologies continue to advance and our understanding of kidney biology deepens, there is hope for patients with genetic kidney disorders to eventually avoid kidney transplantation.</p>","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":" ","pages":""},"PeriodicalIF":14.8,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120162","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 : 2024-08-31DOI: 10.1016/j.kint.2024.08.021
Florian Grahammer , Bernhard Dumoulin , Ramila E. Gulieva , Hui Wu , Yaoxian Xu , Nurgazy Sulaimanov , Frederic Arnold , Lukas Sandner , Tomke Cordts , Abhijeet Todkar , Pierre Moulin , Wilfried Reichardt , Victor G. Puelles , Rafael Kramann , Benjamin S. Freedman , Hauke Busch , Melanie Boerries , Gerd Walz , Tobias B. Huber
Progression of cystic kidney disease has been linked to activation of the mTORC1 signaling pathway. Yet the utility of mTORC1 inhibitors to treat patients with polycystic kidney disease remains controversial despite promising preclinical data. To define the cell intrinsic role of mTORC1 for cyst development, the mTORC1 subunit gene Raptor was selectively inactivated in kidney tubular cells lacking cilia due to simultaneous deletion of the kinesin family member gene Kif3A. In contrast to a rapid onset of cyst formation and kidney failure in mice with defective ciliogenesis, both kidney function, cyst formation discerned by magnetic resonance imaging and overall survival were strikingly improved in mice additionally lacking Raptor. However, these mice eventually succumbed to cystic kidney disease despite mTORC1 inactivation. In-depth transcriptome analysis revealed the rapid activation of other growth-promoting signaling pathways, overriding the effects of mTORC1 deletion and identified cyclin-dependent kinase (CDK) 4 as an alternate driver of cyst growth. Additional inhibition of CDK4-dependent signaling by the CDK4/6 inhibitor Palbociclib markedly slowed disease progression in mice and human organoid models of polycystic kidney disease and potentiated the effects of mTORC1 deletion/inhibition. Our findings indicate that cystic kidneys rapidly adopt bypass mechanisms typically observed in drug resistant cancers. Thus, future clinical trials need to consider combinatorial or sequential therapies to improve therapeutic efficacy in patients with cystic kidney disease.
{"title":"Cyclin-dependent kinase 4 drives cystic kidney disease in the absence of mTORC1 signaling activity","authors":"Florian Grahammer , Bernhard Dumoulin , Ramila E. Gulieva , Hui Wu , Yaoxian Xu , Nurgazy Sulaimanov , Frederic Arnold , Lukas Sandner , Tomke Cordts , Abhijeet Todkar , Pierre Moulin , Wilfried Reichardt , Victor G. Puelles , Rafael Kramann , Benjamin S. Freedman , Hauke Busch , Melanie Boerries , Gerd Walz , Tobias B. Huber","doi":"10.1016/j.kint.2024.08.021","DOIUrl":"10.1016/j.kint.2024.08.021","url":null,"abstract":"<div><div>Progression of cystic kidney disease has been linked to activation of the mTORC1 signaling pathway. Yet the utility of mTORC1 inhibitors to treat patients with polycystic kidney disease remains controversial despite promising preclinical data. To define the cell intrinsic role of mTORC1 for cyst development, the mTORC1 subunit gene <em>Raptor</em> was selectively inactivated in kidney tubular cells lacking cilia due to simultaneous deletion of the kinesin family member gene <em>Kif3A</em>. In contrast to a rapid onset of cyst formation and kidney failure in mice with defective ciliogenesis, both kidney function, cyst formation discerned by magnetic resonance imaging and overall survival were strikingly improved in mice additionally lacking <em>Raptor</em>. However, these mice eventually succumbed to cystic kidney disease despite mTORC1 inactivation. In-depth transcriptome analysis revealed the rapid activation of other growth-promoting signaling pathways, overriding the effects of mTORC1 deletion and identified cyclin-dependent kinase (CDK) 4 as an alternate driver of cyst growth. Additional inhibition of CDK4-dependent signaling by the CDK4/6 inhibitor Palbociclib markedly slowed disease progression in mice and human organoid models of polycystic kidney disease and potentiated the effects of mTORC1 deletion/inhibition. Our findings indicate that cystic kidneys rapidly adopt bypass mechanisms typically observed in drug resistant cancers. Thus, future clinical trials need to consider combinatorial or sequential therapies to improve therapeutic efficacy in patients with cystic kidney disease.</div></div>","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":"106 5","pages":"Pages 856-869"},"PeriodicalIF":14.8,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142108751","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}
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