Sendotypes predict worsening renal function in chronic kidney disease patients

IF 7.9 1区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Clinical and Translational Medicine Pub Date : 2025-03-27 DOI:10.1002/ctm2.70279

Thomas McLarnon, Steven Watterson, Sean McCallion, Eamonn Cooper, Andrew R. English, Ying Kuan, David S. Gibson, Elaine K. Murray, Frank McCarroll, Shu-Dong Zhang, Anthony J. Bjourson, Taranjit Singh Rai

{"title":"Sendotypes predict worsening renal function in chronic kidney disease patients","authors":"Thomas McLarnon, Steven Watterson, Sean McCallion, Eamonn Cooper, Andrew R. English, Ying Kuan, David S. Gibson, Elaine K. Murray, Frank McCarroll, Shu-Dong Zhang, Anthony J. Bjourson, Taranjit Singh Rai","doi":"10.1002/ctm2.70279","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <p>Senescence associated secretory phenotype (SASP) contributes to age-related pathology, however the role of SASP in Chronic Kidney Disease (CKD) is unclear. Here, we employ a variety of omic techniques to show that senescence signatures can separate CKD patients into distinct senescence endotypes (Sendotype).</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>Using specific numbers of senescent proteins, we clustered CKD patients into two distinct sendotypes based on proteomic expression. These clusters were evaluated with three independent criteria assessing inter and intra cluster distances. Differential expression analysis was then performed to investigate differing proteomic expression between sendotypes.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>These clusters accurately stratified CKD patients, with patients in each sendotype having different clinical profiles. Higher expression of these proteins correlated with worsened disease symptomologies. Biological signalling pathways such as TNF, Janus kinase-signal transducers and activators of transcription (JAK-STAT) and NFKB were differentially enriched between patient sendotypes, suggesting potential mechanisms driving the endotype of CKD.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>Our work reveals that, combining clinical features with SASP signatures from CKD patients may help predict whether a patient will have worsening or stable renal trajectory. This has implications for the CKD clinical care pathway and will help clinicians stratify CKD patients accurately.</p>\n </section>\n \n <section>\n \n <h3> Key points</h3>\n \n <div>\n <ul>\n \n <li>Senescent proteins are upregulated in severe patients compared to mild patients</li>\n \n <li>Senescent proteins can stratify patients based on disease severity</li>\n \n <li>High expression of senescent proteins correlates with worsening renal trajectories</li>\n </ul>\n </div>\n </section>\n </div>","PeriodicalId":10189,"journal":{"name":"Clinical and Translational Medicine","volume":"15 4","pages":""},"PeriodicalIF":7.9000,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctm2.70279","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical and Translational Medicine","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/ctm2.70279","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}

引用次数: 0

Abstract

Background

Senescence associated secretory phenotype (SASP) contributes to age-related pathology, however the role of SASP in Chronic Kidney Disease (CKD) is unclear. Here, we employ a variety of omic techniques to show that senescence signatures can separate CKD patients into distinct senescence endotypes (Sendotype).

Methods

Using specific numbers of senescent proteins, we clustered CKD patients into two distinct sendotypes based on proteomic expression. These clusters were evaluated with three independent criteria assessing inter and intra cluster distances. Differential expression analysis was then performed to investigate differing proteomic expression between sendotypes.

Results

These clusters accurately stratified CKD patients, with patients in each sendotype having different clinical profiles. Higher expression of these proteins correlated with worsened disease symptomologies. Biological signalling pathways such as TNF, Janus kinase-signal transducers and activators of transcription (JAK-STAT) and NFKB were differentially enriched between patient sendotypes, suggesting potential mechanisms driving the endotype of CKD.

Conclusion

Our work reveals that, combining clinical features with SASP signatures from CKD patients may help predict whether a patient will have worsening or stable renal trajectory. This has implications for the CKD clinical care pathway and will help clinicians stratify CKD patients accurately.

Key points

Senescent proteins are upregulated in severe patients compared to mild patients
Senescent proteins can stratify patients based on disease severity
High expression of senescent proteins correlates with worsening renal trajectories

Abstract Image

查看原文本刊更多论文

求助全文

约1分钟内获得全文求助全文

来源期刊

Clinical and Translational Medicine Multiple-

CiteScore

15.90

自引率

1.90%

发文量

450

审稿时长

4 weeks

期刊介绍： Clinical and Translational Medicine (CTM) is an international, peer-reviewed, open-access journal dedicated to accelerating the translation of preclinical research into clinical applications and fostering communication between basic and clinical scientists. It highlights the clinical potential and application of various fields including biotechnologies, biomaterials, bioengineering, biomarkers, molecular medicine, omics science, bioinformatics, immunology, molecular imaging, drug discovery, regulation, and health policy. With a focus on the bench-to-bedside approach, CTM prioritizes studies and clinical observations that generate hypotheses relevant to patients and diseases, guiding investigations in cellular and molecular medicine. The journal encourages submissions from clinicians, researchers, policymakers, and industry professionals.