Jonathan G. Amatruda , Ronit Katz , Casey M. Rebholz , Mark J. Sarnak , Orlando M. Gutierrez , Sarah J. Schrauben , Jason H. Greenberg , Josef Coresh , Mary Cushman , Sushrut Waikar , Chirag R. Parikh , Jeffrey R. Schelling , Manasi P. Jogalekar , Joseph V. Bonventre , Ramachandran S. Vasan , Paul L. Kimmel , Joachim H. Ix , Michael G. Shlipak , CKD Biomarkers Consortium
{"title":"无糖尿病者肾小管健康的尿液生物标记物与发生慢性肾脏病的风险：ARIC、MESA 和 REGARDS 研究","authors":"Jonathan G. Amatruda , Ronit Katz , Casey M. Rebholz , Mark J. Sarnak , Orlando M. Gutierrez , Sarah J. Schrauben , Jason H. Greenberg , Josef Coresh , Mary Cushman , Sushrut Waikar , Chirag R. Parikh , Jeffrey R. Schelling , Manasi P. Jogalekar , Joseph V. Bonventre , Ramachandran S. Vasan , Paul L. Kimmel , Joachim H. Ix , Michael G. Shlipak , CKD Biomarkers Consortium","doi":"10.1016/j.xkme.2024.100834","DOIUrl":null,"url":null,"abstract":"<div><h3>Rationale & Objective</h3><p>Tubulointerstitial damage is a feature of early chronic kidney disease (CKD), but current clinical tests capture it poorly. Urine biomarkers of tubulointerstitial health may identify risk of CKD.</p></div><div><h3>Study Design</h3><p>Prospective cohort (Atherosclerosis Risk in Communities [ARIC]) and case-cohort (Multi-Ethnic Study of Atherosclerosis [MESA] and Reasons for Geographic and Racial Differences in Stroke [REGARDS]).</p></div><div><h3>Setting & Participants</h3><p>Adults with estimated glomerular filtration rate (eGFR) ≥60<!--> <!-->mL/min/1.73<!--> <!-->m<sup>2</sup> and without diabetes in the ARIC, REGARDS, and MESA studies.</p></div><div><h3>Exposures</h3><p>Baseline urine monocyte chemoattractant protein-1 (MCP-1), alpha-1-microglobulin (α1m), kidney injury molecule-1, epidermal growth factor, and chitinase-3-like protein 1.</p></div><div><h3>Outcome</h3><p>Incident CKD or end-stage kidney disease.</p></div><div><h3>Analytical Approach</h3><p>Multivariable Cox proportional hazards regression for each cohort; meta-analysis of results from all 3 cohorts.</p></div><div><h3>Results</h3><p>872 ARIC participants (444 cases of incident CKD), 636 MESA participants (158 cases), and 924 REGARDS participants (488 cases) were sampled. Across cohorts, mean age ranged from 60<!--> <!-->±<!--> <!-->10 to 63<!--> <!-->±<!--> <!-->8 years, and baseline eGFR ranged from 88<!--> <!-->±<!--> <!-->13 to 91<!--> <!-->±<!--> <!-->14<!--> <!-->mL/min/1.73<!--> <!-->m<sup>2</sup>. In ARIC, higher concentrations of urine MCP-1, α1m, and kidney injury molecule-1 were associated with incident CKD. In MESA, higher concentration of urine MCP-1 and lower concentration of epidermal growth factor were each associated with incident CKD. In REGARDS, none of the biomarkers were associated with incident CKD. In meta-analysis of all 3 cohorts, each 2-fold increase α1m concentration was associated with incident CKD (HR, 1.19; 95% CI, 1.08-1.31).</p></div><div><h3>Limitations</h3><p>Observational design susceptible to confounding; competing risks during long follow-up period; meta-analysis limited to 3 cohorts.</p></div><div><h3>Conclusions</h3><p>In 3 combined cohorts of adults without prevalent CKD or diabetes, higher urine α1m concentration was independently associated with incident CKD. 4 biomarkers were associated with incident CKD in at least 1 of the cohorts when analyzed individually. Kidney tubule health markers might inform CKD risk independent of eGFR and albuminuria.</p></div><div><h3>Plain-Language Summary</h3><p>This study analyzed 3 cohorts (ARIC, MESA, and REGARDS) of adults without diabetes or prevalent chronic kidney disease (CKD) to determine the associations of 5 urinary biomarkers of kidney tubulointerstitial health with incident CKD, independent of traditional measures of kidney health. Meta-analysis of results from all 3 cohorts suggested that higher baseline levels of urine alpha-1-microglobulin were associated with incident CKD at follow-up. Results from individual cohorts suggested that in addition to alpha-1-microglobulin, monocyte chemoattractant protein-1, kidney injury molecule-1, and epidermal growth factor may also be associated with the development of CKD. These findings underscore the importance of kidney tubule interstitial health in defining risk of CKD independent of creatinine and urine albumin.</p></div>","PeriodicalId":17885,"journal":{"name":"Kidney Medicine","volume":null,"pages":null},"PeriodicalIF":3.2000,"publicationDate":"2024-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590059524000451/pdfft?md5=9677af2a2936700dedd06ff7f9bd6d04&pid=1-s2.0-S2590059524000451-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Urine Biomarkers of Kidney Tubule Health and Risk of Incident CKD in Persons Without Diabetes: The ARIC, MESA, and REGARDS Studies\",\"authors\":\"Jonathan G. Amatruda , Ronit Katz , Casey M. Rebholz , Mark J. Sarnak , Orlando M. Gutierrez , Sarah J. Schrauben , Jason H. Greenberg , Josef Coresh , Mary Cushman , Sushrut Waikar , Chirag R. Parikh , Jeffrey R. Schelling , Manasi P. Jogalekar , Joseph V. Bonventre , Ramachandran S. Vasan , Paul L. Kimmel , Joachim H. Ix , Michael G. Shlipak , CKD Biomarkers Consortium\",\"doi\":\"10.1016/j.xkme.2024.100834\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Rationale & Objective</h3><p>Tubulointerstitial damage is a feature of early chronic kidney disease (CKD), but current clinical tests capture it poorly. Urine biomarkers of tubulointerstitial health may identify risk of CKD.</p></div><div><h3>Study Design</h3><p>Prospective cohort (Atherosclerosis Risk in Communities [ARIC]) and case-cohort (Multi-Ethnic Study of Atherosclerosis [MESA] and Reasons for Geographic and Racial Differences in Stroke [REGARDS]).</p></div><div><h3>Setting & Participants</h3><p>Adults with estimated glomerular filtration rate (eGFR) ≥60<!--> <!-->mL/min/1.73<!--> <!-->m<sup>2</sup> and without diabetes in the ARIC, REGARDS, and MESA studies.</p></div><div><h3>Exposures</h3><p>Baseline urine monocyte chemoattractant protein-1 (MCP-1), alpha-1-microglobulin (α1m), kidney injury molecule-1, epidermal growth factor, and chitinase-3-like protein 1.</p></div><div><h3>Outcome</h3><p>Incident CKD or end-stage kidney disease.</p></div><div><h3>Analytical Approach</h3><p>Multivariable Cox proportional hazards regression for each cohort; meta-analysis of results from all 3 cohorts.</p></div><div><h3>Results</h3><p>872 ARIC participants (444 cases of incident CKD), 636 MESA participants (158 cases), and 924 REGARDS participants (488 cases) were sampled. Across cohorts, mean age ranged from 60<!--> <!-->±<!--> <!-->10 to 63<!--> <!-->±<!--> <!-->8 years, and baseline eGFR ranged from 88<!--> <!-->±<!--> <!-->13 to 91<!--> <!-->±<!--> <!-->14<!--> <!-->mL/min/1.73<!--> <!-->m<sup>2</sup>. In ARIC, higher concentrations of urine MCP-1, α1m, and kidney injury molecule-1 were associated with incident CKD. In MESA, higher concentration of urine MCP-1 and lower concentration of epidermal growth factor were each associated with incident CKD. In REGARDS, none of the biomarkers were associated with incident CKD. In meta-analysis of all 3 cohorts, each 2-fold increase α1m concentration was associated with incident CKD (HR, 1.19; 95% CI, 1.08-1.31).</p></div><div><h3>Limitations</h3><p>Observational design susceptible to confounding; competing risks during long follow-up period; meta-analysis limited to 3 cohorts.</p></div><div><h3>Conclusions</h3><p>In 3 combined cohorts of adults without prevalent CKD or diabetes, higher urine α1m concentration was independently associated with incident CKD. 4 biomarkers were associated with incident CKD in at least 1 of the cohorts when analyzed individually. Kidney tubule health markers might inform CKD risk independent of eGFR and albuminuria.</p></div><div><h3>Plain-Language Summary</h3><p>This study analyzed 3 cohorts (ARIC, MESA, and REGARDS) of adults without diabetes or prevalent chronic kidney disease (CKD) to determine the associations of 5 urinary biomarkers of kidney tubulointerstitial health with incident CKD, independent of traditional measures of kidney health. Meta-analysis of results from all 3 cohorts suggested that higher baseline levels of urine alpha-1-microglobulin were associated with incident CKD at follow-up. Results from individual cohorts suggested that in addition to alpha-1-microglobulin, monocyte chemoattractant protein-1, kidney injury molecule-1, and epidermal growth factor may also be associated with the development of CKD. These findings underscore the importance of kidney tubule interstitial health in defining risk of CKD independent of creatinine and urine albumin.</p></div>\",\"PeriodicalId\":17885,\"journal\":{\"name\":\"Kidney Medicine\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.2000,\"publicationDate\":\"2024-04-26\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S2590059524000451/pdfft?md5=9677af2a2936700dedd06ff7f9bd6d04&pid=1-s2.0-S2590059524000451-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Kidney Medicine\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2590059524000451\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"UROLOGY & NEPHROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Kidney Medicine","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2590059524000451","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"UROLOGY & NEPHROLOGY","Score":null,"Total":0}
Urine Biomarkers of Kidney Tubule Health and Risk of Incident CKD in Persons Without Diabetes: The ARIC, MESA, and REGARDS Studies
Rationale & Objective
Tubulointerstitial damage is a feature of early chronic kidney disease (CKD), but current clinical tests capture it poorly. Urine biomarkers of tubulointerstitial health may identify risk of CKD.
Study Design
Prospective cohort (Atherosclerosis Risk in Communities [ARIC]) and case-cohort (Multi-Ethnic Study of Atherosclerosis [MESA] and Reasons for Geographic and Racial Differences in Stroke [REGARDS]).
Setting & Participants
Adults with estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 and without diabetes in the ARIC, REGARDS, and MESA studies.
Exposures
Baseline urine monocyte chemoattractant protein-1 (MCP-1), alpha-1-microglobulin (α1m), kidney injury molecule-1, epidermal growth factor, and chitinase-3-like protein 1.
Outcome
Incident CKD or end-stage kidney disease.
Analytical Approach
Multivariable Cox proportional hazards regression for each cohort; meta-analysis of results from all 3 cohorts.
Results
872 ARIC participants (444 cases of incident CKD), 636 MESA participants (158 cases), and 924 REGARDS participants (488 cases) were sampled. Across cohorts, mean age ranged from 60 ± 10 to 63 ± 8 years, and baseline eGFR ranged from 88 ± 13 to 91 ± 14 mL/min/1.73 m2. In ARIC, higher concentrations of urine MCP-1, α1m, and kidney injury molecule-1 were associated with incident CKD. In MESA, higher concentration of urine MCP-1 and lower concentration of epidermal growth factor were each associated with incident CKD. In REGARDS, none of the biomarkers were associated with incident CKD. In meta-analysis of all 3 cohorts, each 2-fold increase α1m concentration was associated with incident CKD (HR, 1.19; 95% CI, 1.08-1.31).
Limitations
Observational design susceptible to confounding; competing risks during long follow-up period; meta-analysis limited to 3 cohorts.
Conclusions
In 3 combined cohorts of adults without prevalent CKD or diabetes, higher urine α1m concentration was independently associated with incident CKD. 4 biomarkers were associated with incident CKD in at least 1 of the cohorts when analyzed individually. Kidney tubule health markers might inform CKD risk independent of eGFR and albuminuria.
Plain-Language Summary
This study analyzed 3 cohorts (ARIC, MESA, and REGARDS) of adults without diabetes or prevalent chronic kidney disease (CKD) to determine the associations of 5 urinary biomarkers of kidney tubulointerstitial health with incident CKD, independent of traditional measures of kidney health. Meta-analysis of results from all 3 cohorts suggested that higher baseline levels of urine alpha-1-microglobulin were associated with incident CKD at follow-up. Results from individual cohorts suggested that in addition to alpha-1-microglobulin, monocyte chemoattractant protein-1, kidney injury molecule-1, and epidermal growth factor may also be associated with the development of CKD. These findings underscore the importance of kidney tubule interstitial health in defining risk of CKD independent of creatinine and urine albumin.
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