Kidney international最新文献

Repression of peroxisome proliferation-activated receptor γ coactivator-1α by p53 after kidney injury promotes mitochondrial damage and maladaptive kidney repair.

IF 14.8 1区医学

Kidney international Pub Date : 2025-02-24 DOI: 10.1016/j.kint.2025.02.009

Ying Wang, Yuqing Zeng, Ying Fu, Zhiwen Liu, Xiaoru Hu, Chengyuan Tang, Juan Cai, Zheng Dong

{"title":"Repression of peroxisome proliferation-activated receptor γ coactivator-1α by p53 after kidney injury promotes mitochondrial damage and maladaptive kidney repair.","authors":"Ying Wang, Yuqing Zeng, Ying Fu, Zhiwen Liu, Xiaoru Hu, Chengyuan Tang, Juan Cai, Zheng Dong","doi":"10.1016/j.kint.2025.02.009","DOIUrl":"https://doi.org/10.1016/j.kint.2025.02.009","url":null,"abstract":"Maladaptive kidney repair after injury is associated with a loss of mitochondrial homeostasis, but the underlying mechanism is largely unknown. Moreover, it remains unclear whether this mitochondrial change contributes to maladaptive kidney repair or the development of chronic kidney problems after injury. Here, we report that the transcriptional coactivator peroxisome proliferation-activated receptor γ coactivator-1α (PGC1α), a master regulator of mitochondrial biogenesis, was persistently downregulated during maladaptive kidney repair after repeated low-dose cisplatin nephrotoxicity or unilateral ischemia/reperfusion injury. Administration of the PGC1α activator ZLN005 after either kidney injury not only preserved mitochondria but also attenuated kidney dysfunction, tubular damage, interstitial fibrosis, and inflammation. PGC1α downregulation in these models was associated with p53 activation. Notably, knockout of p53 from proximal tubules prevented PGC1α downregulation, attenuated chronic kidney pathologies and minimized functional decline. Inhibition of p53 with pifithrin-α, a cell permeable p53 inhibitor, had similar effects. Mechanistically, p53 bound to the PGC1α gene promoter during maladaptive kidney repair and this binding was suppressed by pifithrin-α. Together, our results indicate that p53 is induced during maladaptive kidney repair to repress PGC1α transcriptionally, resulting in mitochondrial dysfunction for the development of chronic kidney problems. Activation of PGC1α and inhibition of p53 may improve kidney repair after injury and prevent the development of chronic kidney problems.","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":" ","pages":""},"PeriodicalIF":14.8,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515879","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}

引用次数: 0

Guanidinylation compromises the anti-inflammatory and anti-oxidative properties of apolipoprotein A-I in chronic kidney disease progression.

IF 14.8 1区医学

Kidney international Pub Date : 2025-02-24 DOI: 10.1016/j.kint.2025.02.010

Andrea Bonnin-Marquez, Joachim Jankowski, Sanne L Maas, Juliane Hermann, Florian Kahles, Michaela Lellig, Danilo Fliser, Stefan Schunk, Eleni Stamellou, Martin Berger, Thimoteus Speer, Sahir Kalim, Dickson Wai Leong Wong, Emiel P C van der Vorst, Vera Jankowski

{"title":"Guanidinylation compromises the anti-inflammatory and anti-oxidative properties of apolipoprotein A-I in chronic kidney disease progression.","authors":"Andrea Bonnin-Marquez, Joachim Jankowski, Sanne L Maas, Juliane Hermann, Florian Kahles, Michaela Lellig, Danilo Fliser, Stefan Schunk, Eleni Stamellou, Martin Berger, Thimoteus Speer, Sahir Kalim, Dickson Wai Leong Wong, Emiel P C van der Vorst, Vera Jankowski","doi":"10.1016/j.kint.2025.02.010","DOIUrl":"https://doi.org/10.1016/j.kint.2025.02.010","url":null,"abstract":"Chronic kidney disease (CKD) substantially heightens the likelihood of cardiovascular events, in part due to the impaired functionality of high-density lipoprotein (HDL) and its connection with atherosclerosis. Here, 82 patients with CKD stages 2-5 had their plasma isolated and analyzed using mass spectrometry to detect post-translational modifications of apolipoprotein A-I (apoA-I), the main protein component of HDL. Guanidinylation, a non-enzymatic post-translational modification, led to increased levels of apoA-I with CKD progression. The increase in guanidinylated apoA-I became significant from CKD stage 3 onwards. The modification patterns of apoA-I in patients with CKD were mimicked in vitro by exposure to O-methylisourea bisulfate. The thus modified apoA-I was used for functional assays which revealed that guanidinylation compromised the anti-inflammatory and anti-oxidative properties of apoA-I,of potential relevance for clinical findings. Specifically, guanidinylated apoA-I activated inflammatory kinases in macrophages, suggesting a mechanistic link between apoA-I modifications and inflammatory responses. These findings are in favor of alterations in the functional properties of apoA-I in patients with CKD due to guanidinylation. The identification of high guanidinylated apoA-I peptide levels in plasma highlights a novel aspect of protein modification in CKD pathophysiology. The results of our study may provide a better understanding of the molecular mechanisms underlying CKD-related cardiovascular complications and highlight the importance and the need to minimize post-translational modifications in patients with CKD.","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":" ","pages":""},"PeriodicalIF":14.8,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515895","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}

引用次数: 0

Somatic mutations acquired during life: state of the art and implications for the kidney.

IF 14.8 1区医学

Kidney international Pub Date : 2025-02-21 DOI: 10.1016/j.kint.2024.10.036

Jean Piero Margaria, Sipontina Faienza, Irene Franco

{"title":"Somatic mutations acquired during life: state of the art and implications for the kidney.","authors":"Jean Piero Margaria, Sipontina Faienza, Irene Franco","doi":"10.1016/j.kint.2024.10.036","DOIUrl":"https://doi.org/10.1016/j.kint.2024.10.036","url":null,"abstract":"As a consequence of continuous interaction with mutagens, the genome sequence accumulates changes, which are referred to as \"somatic mutations\". Somatic variants acquired by normal cells during a lifetime are difficult to detect with common sequencing methods. This review provides a basic description of currently available technologies for somatic mutation detection and summarizes the studies that have explored somatic mutation in the kidneys. Given the role of somatic mutations in the formation of kidney cysts, genomic analyses can be used to investigate mechanisms that influence disease progression in inherited cystic kidney disorders. Moreover, genomic analyses are an important method to explore the evolution from a normal cell to cancer, providing insights into mechanisms of tumor initiation. Somatic mutation data can be used to discover endogenous and exogenous mutagens that harness the kidneys, including tobacco and aristolochic acid. In addition, genomic analyses have highlighted a link between kidney damage and mutation. This information is going to be key for understanding life-style factors that influence kidney cancer risk, overall impacting clinical decisions and public health strategies.","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":" ","pages":""},"PeriodicalIF":14.8,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483178","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}

引用次数: 0

THE PREVENTION AND MANAGEMENT OF CHRONIC KIDNEY DISEASE AMONG PATIENTS WITH METABOLIC SYNDROME.

IF 14.8 1区医学

Kidney international Pub Date : 2025-02-20 DOI: 10.1016/j.kint.2024.12.021

Doreen Zhu, Parminder K Judge, Christoph Wanner, Richard Haynes, William G Herrington

{"title":"THE PREVENTION AND MANAGEMENT OF CHRONIC KIDNEY DISEASE AMONG PATIENTS WITH METABOLIC SYNDROME.","authors":"Doreen Zhu, Parminder K Judge, Christoph Wanner, Richard Haynes, William G Herrington","doi":"10.1016/j.kint.2024.12.021","DOIUrl":"https://doi.org/10.1016/j.kint.2024.12.021","url":null,"abstract":"Treatment of patients with chronic kidney disease (CKD) requires implementation of prevention and management strategies that reduce the risk of kidney failure and CKD-associated cardiovascular risk. Metabolic syndrome is characterised by obesity, high blood pressure, dyslipidaemia and hyperglycaemia, and is common among patients with CKD. Large-scale randomised trials have led to significant advances in the management of CKD with five pharmacotherapies now proven to be nephroprotective and/or cardioprotective in certain types of patients. Renin-angiotensin system inhibitors and sodium-glucose co-transporter 2 inhibitors slow kidney disease progression and reduce heart failure complications for most patients with CKD. In addition, statin-based regimens lower low-density lipoprotein cholesterol and reduce the risk of atherosclerotic disease (with no clinically meaningful effect on kidney outcomes). For patients with type 2 diabetes and albuminuric CKD, the non-steroidal mineralocorticoid receptor antagonist finerenone and the glucagon-like peptide-1 receptor agonist semaglutide also confer cardiorenal benefits, with semaglutide additionally effective at reducing weight. Together, these randomised data strongly suggest that metabolic syndrome mediates some of the cardiorenal risk observed in CKD. Considered separately, the trials help elucidate which components of metabolic syndrome influence the pathophysiology of kidney disease progression and which separately modify risk of atherosclerotic and non-atherosclerotic cardiovascular outcomes. As we predict complementary and different mechanisms of nephroprotection and cardioprotection for these different interventions, it seems logical that they should be deployed together to maximise benefits. Even when combined, however, these therapies are not a cure so further trials remain important to reduce the residual cardiorenal risks associated with CKD.","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":" ","pages":""},"PeriodicalIF":14.8,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476802","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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IF 14.8 1区医学

Kidney international Pub Date : 2025-02-19 DOI: 10.1016/j.kint.2024.11.018

Krishna A. Agarwal , Lesley A. Inker , Andrew S. Levey

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Age- and sex-dependent kidney failure risk in 25- to 95-year-old Germans

IF 14.8 1区医学

Kidney international Pub Date : 2025-02-19 DOI: 10.1016/j.kint.2024.12.005

Friedrich A. von Samson-Himmelstjerna , Edgar Steiger , Benedikt Kolbrink , Roland Schmitt , Thomas Czihal , Dominik von Stillfried , Kevin Schulte

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