Molly C Fisher, Rebecca Scherzer, Merve Postalcioglu, Teresa K Chen, Simon B Ascher, Jordan E Lake, Michelle Floris-Morre, Seble Kassaye, Igho Ofotokun, Jodie Dionne, Maria Alcaide, Mardge Cohen, Deborah Gustafson, Alison G Abraham, Joseph B Margolick, Ken Ho, Valentina Stosor, Phyllis C Tien, Michael Shlipak, Michelle M Estrella
{"title":"HIV感染者肾小管健康血浆生物标志物重复测量与纵向肾功能的关系","authors":"Molly C Fisher, Rebecca Scherzer, Merve Postalcioglu, Teresa K Chen, Simon B Ascher, Jordan E Lake, Michelle Floris-Morre, Seble Kassaye, Igho Ofotokun, Jodie Dionne, Maria Alcaide, Mardge Cohen, Deborah Gustafson, Alison G Abraham, Joseph B Margolick, Ken Ho, Valentina Stosor, Phyllis C Tien, Michael Shlipak, Michelle M Estrella","doi":"10.1097/QAD.0000000000004359","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>In people with HIV (PWH), urine tubular biomarkers have been linked to kidney function decline, but urine concentration variability limits their clinical utility. Plasma biomarkers may offer more stable indicators of kidney tubular health.</p><p><strong>Methods: </strong>We conducted a case-cohort study of 440 PWH from the MACS/WIHS Combined Cohort Study. Cases developed rapid kidney function decline (RKFD: ≥30% eGFR reduction). We measured plasma biomarkers of tubular injury (KIM-1), inflammation (TNFr1, TNFr2), and synthetic function (UMOD, EGF) at baseline and year 2. Associations with RKFD were assessed using multivariable risk regression, adjusting for CKD and HIV-related risk factors, eGFR, and albuminuria. In a random sub-cohort, linear mixed models evaluated associations with annualized eGFR change.</p><p><strong>Results: </strong>At baseline, median age was 49 years; 33% were women; 69% were virally suppressed; eGFR was similar in cases vs. non-cases (93 vs. 94 mL/min/1.73m2). Over a median of 4.5 years, 172 RKFD events occurred. Each 1-standard deviation higher baseline KIM-1, TNFr1, TNFr2, UMOD and EGF level was associated with adjusted relative risks (RR) for RKFD of 1.26 (95%CI: 1.15-1.39), 1.39 (1.24-1.55), 1.40 (1.24-1.57), 0.84 (0.77-0.93) and 0.85 (0.78-0.92), respectively. Findings were similar at year 2 and for 2-year biomarker changes. In joint models, baseline KIM-1, TNFr2, and UMOD remained independently associated with RKFD (RR: 1.19 [1.08-1.31], 1.27 [1.12-1.43], and 0.86 [0.78-0.95]), respectively. No biomarker was associated with annualized eGFR change in the sub-cohort.</p><p><strong>Conclusion: </strong>In PWH, plasma biomarkers reflecting impaired kidney tubular health were independently associated with RKFD and may be useful prognosticators of adverse kidney outcomes.</p>","PeriodicalId":7502,"journal":{"name":"AIDS","volume":" ","pages":""},"PeriodicalIF":3.1000,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Associations of repeated measures of plasma biomarkers of kidney tubular health with longitudinal kidney function in people with HIV.\",\"authors\":\"Molly C Fisher, Rebecca Scherzer, Merve Postalcioglu, Teresa K Chen, Simon B Ascher, Jordan E Lake, Michelle Floris-Morre, Seble Kassaye, Igho Ofotokun, Jodie Dionne, Maria Alcaide, Mardge Cohen, Deborah Gustafson, Alison G Abraham, Joseph B Margolick, Ken Ho, Valentina Stosor, Phyllis C Tien, Michael Shlipak, Michelle M Estrella\",\"doi\":\"10.1097/QAD.0000000000004359\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>In people with HIV (PWH), urine tubular biomarkers have been linked to kidney function decline, but urine concentration variability limits their clinical utility. Plasma biomarkers may offer more stable indicators of kidney tubular health.</p><p><strong>Methods: </strong>We conducted a case-cohort study of 440 PWH from the MACS/WIHS Combined Cohort Study. Cases developed rapid kidney function decline (RKFD: ≥30% eGFR reduction). We measured plasma biomarkers of tubular injury (KIM-1), inflammation (TNFr1, TNFr2), and synthetic function (UMOD, EGF) at baseline and year 2. Associations with RKFD were assessed using multivariable risk regression, adjusting for CKD and HIV-related risk factors, eGFR, and albuminuria. In a random sub-cohort, linear mixed models evaluated associations with annualized eGFR change.</p><p><strong>Results: </strong>At baseline, median age was 49 years; 33% were women; 69% were virally suppressed; eGFR was similar in cases vs. non-cases (93 vs. 94 mL/min/1.73m2). Over a median of 4.5 years, 172 RKFD events occurred. Each 1-standard deviation higher baseline KIM-1, TNFr1, TNFr2, UMOD and EGF level was associated with adjusted relative risks (RR) for RKFD of 1.26 (95%CI: 1.15-1.39), 1.39 (1.24-1.55), 1.40 (1.24-1.57), 0.84 (0.77-0.93) and 0.85 (0.78-0.92), respectively. Findings were similar at year 2 and for 2-year biomarker changes. In joint models, baseline KIM-1, TNFr2, and UMOD remained independently associated with RKFD (RR: 1.19 [1.08-1.31], 1.27 [1.12-1.43], and 0.86 [0.78-0.95]), respectively. No biomarker was associated with annualized eGFR change in the sub-cohort.</p><p><strong>Conclusion: </strong>In PWH, plasma biomarkers reflecting impaired kidney tubular health were independently associated with RKFD and may be useful prognosticators of adverse kidney outcomes.</p>\",\"PeriodicalId\":7502,\"journal\":{\"name\":\"AIDS\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":3.1000,\"publicationDate\":\"2025-09-24\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"AIDS\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1097/QAD.0000000000004359\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"AIDS","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/QAD.0000000000004359","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
Associations of repeated measures of plasma biomarkers of kidney tubular health with longitudinal kidney function in people with HIV.
Background: In people with HIV (PWH), urine tubular biomarkers have been linked to kidney function decline, but urine concentration variability limits their clinical utility. Plasma biomarkers may offer more stable indicators of kidney tubular health.
Methods: We conducted a case-cohort study of 440 PWH from the MACS/WIHS Combined Cohort Study. Cases developed rapid kidney function decline (RKFD: ≥30% eGFR reduction). We measured plasma biomarkers of tubular injury (KIM-1), inflammation (TNFr1, TNFr2), and synthetic function (UMOD, EGF) at baseline and year 2. Associations with RKFD were assessed using multivariable risk regression, adjusting for CKD and HIV-related risk factors, eGFR, and albuminuria. In a random sub-cohort, linear mixed models evaluated associations with annualized eGFR change.
Results: At baseline, median age was 49 years; 33% were women; 69% were virally suppressed; eGFR was similar in cases vs. non-cases (93 vs. 94 mL/min/1.73m2). Over a median of 4.5 years, 172 RKFD events occurred. Each 1-standard deviation higher baseline KIM-1, TNFr1, TNFr2, UMOD and EGF level was associated with adjusted relative risks (RR) for RKFD of 1.26 (95%CI: 1.15-1.39), 1.39 (1.24-1.55), 1.40 (1.24-1.57), 0.84 (0.77-0.93) and 0.85 (0.78-0.92), respectively. Findings were similar at year 2 and for 2-year biomarker changes. In joint models, baseline KIM-1, TNFr2, and UMOD remained independently associated with RKFD (RR: 1.19 [1.08-1.31], 1.27 [1.12-1.43], and 0.86 [0.78-0.95]), respectively. No biomarker was associated with annualized eGFR change in the sub-cohort.
Conclusion: In PWH, plasma biomarkers reflecting impaired kidney tubular health were independently associated with RKFD and may be useful prognosticators of adverse kidney outcomes.
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Publishing the very latest ground breaking research on HIV and AIDS. Read by all the top clinicians and researchers, AIDS has the highest impact of all AIDS-related journals. With 18 issues per year, AIDS guarantees the authoritative presentation of significant advances. The Editors, themselves noted international experts who know the demands of your work, are committed to making AIDS the most distinguished and innovative journal in the field. Submitted articles undergo a preliminary review by the editor. Some articles may be returned to authors without further consideration. Those being considered for publication will undergo further assessment and peer-review by the editors and those invited to do so from a reviewer pool.
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