{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T18:16:29Z","timestamp":1774980989857,"version":"3.50.1"},"reference-count":45,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2020,5,31]],"date-time":"2020-05-31T00:00:00Z","timestamp":1590883200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000097","name":"National Center for Research Resources","doi-asserted-by":"publisher","award":["RR07122"],"award-info":[{"award-number":["RR07122"]}],"id":[{"id":"10.13039\/100000097","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["TR001420"],"award-info":[{"award-number":["TR001420"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["HL146818"],"award-info":[{"award-number":["HL146818"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["14GRNT20480131"],"award-info":[{"award-number":["14GRNT20480131"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["18TPA34170522"],"award-info":[{"award-number":["18TPA34170522"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["HD047584"],"award-info":[{"award-number":["HD047584"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["HD084227"],"award-info":[{"award-number":["HD084227"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Clinical Hypertension"],"published-print":{"date-parts":[[2020,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Early\u2010life factors including preterm birth and VLBW increase the risk of hypertension, but the mechanisms remain poorly understood. Reductions in the anti\u2010aging protein \u03b1\u2010klotho are associated with hypertension, possibly due to angiotensin (Ang) II activation, but the mechanisms are incompletely understood and clinical evidence is lacking. The association of \u03b1\u2010klotho with the alternative Ang\u2010(1\u20107) pathway, which counteracts Ang II to lower BP, is undescribed. We hypothesized that lower urinary \u03b1\u2010klotho is associated with higher BP and lower urinary Ang\u2010(1\u20107) in preterm\u2010born VLBW young adults. In a cross\u2010sectional analysis of data from a prospective cohort of 141 preterm\u2010born VLBW young adults, we assessed the associations among urinary \u03b1\u2010klotho\/creatinine, Ang II\/creatinine, Ang\u2010(1\u20107)\/creatinine, Ang II\/Ang\u2010(1\u20107), and BP using generalized linear models adjusted for age and hypertensive pregnancy and conducted a sensitivity analysis in 32 term\u2010born young adults. Among those born preterm, lower \u03b1\u2010klotho\/creatinine was associated with higher systolic BP (adjusted <jats:italic>\u03b2<\/jats:italic> (a<jats:italic>\u03b2<\/jats:italic>): \u22122.58\u00a0mm\u00a0Hg, 95% CI \u22124.99 to \u22120.17), lower Ang\u2010(1\u20107)\/creatinine (ln a<jats:italic>\u03b2<\/jats:italic>: 0.1, 0.04\u20100.16), and higher Ang II\/Ang\u2010(1\u20107) (ln a<jats:italic>\u03b2<\/jats:italic>: \u22120.14, \u22120.21 to \u22120.07). In term\u2010born participants, \u03b1\u2010klotho\/creatinine was inversely associated with Ang II\/creatinine (ln a<jats:italic>\u03b2<\/jats:italic>: \u22120.15, \u22120.27 to \u22120.03) and Ang II\/Ang\u2010(1\u20107) (ln a<jats:italic>\u03b2<\/jats:italic>: \u22120.15, \u22120.27 to \u22120.03). In preterm\u2010born young adults with VLBW, lower urinary \u03b1\u2010klotho\/creatinine was associated with higher SBP, lower urinary Ang\u2010(1\u20107)\/creatinine, and higher urinary Ang II\/Ang\u2010(1\u20107). Reduced renal \u03b1\u2010klotho expression could lead to renal Ang\u2010(1\u20107) suppression as a novel mechanism for the development of hypertension among individuals born preterm with VLBW.<\/jats:p>","DOI":"10.1111\/jch.13897","type":"journal-article","created":{"date-parts":[[2020,5,31]],"date-time":"2020-05-31T17:53:51Z","timestamp":1590947631000},"page":"1033-1040","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Lower urinary \u03b1\u2010Klotho is associated with lower angiotensin\u2010(1\u20107) and higher blood pressure in young adults born preterm with very low birthweight"],"prefix":"10.1111","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3204-4142","authenticated-orcid":false,"given":"Andrew M.","family":"South","sequence":"first","affiliation":[{"name":"Department of Pediatrics Wake Forest School of Medicine and Brenner Children's Hospital Winston Salem North Carolina USA"},{"name":"Cardiovascular Sciences Center Wake Forest School of Medicine Winston Salem North Carolina USA"},{"name":"Department of Epidemiology and Prevention Division of Public Health Sciences Wake Forest School of Medicine Winston Salem North Carolina USA"},{"name":"Department of Surgery\u2010Hypertension and Vascular Research Wake Forest School of Medicine Winston Salem North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hossam A.","family":"Shaltout","sequence":"additional","affiliation":[{"name":"Cardiovascular Sciences Center Wake Forest School of Medicine Winston Salem North Carolina USA"},{"name":"Department of Obstetrics and Gynecology Wake Forest School of Medicine Winston Salem North Carolina USA"},{"name":"Department of Pharmacology and Toxicology School of Pharmacy University of Alexandria Alexandria Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"TanYa M.","family":"Gwathmey","sequence":"additional","affiliation":[{"name":"Cardiovascular Sciences Center Wake Forest School of Medicine Winston Salem North Carolina USA"},{"name":"Department of Surgery\u2010Hypertension and Vascular Research Wake Forest School of Medicine Winston Salem North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth T.","family":"Jensen","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Prevention Division of Public Health Sciences Wake Forest School of Medicine Winston Salem North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patricia A.","family":"Nixon","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Wake Forest School of Medicine and Brenner Children's Hospital Winston Salem North Carolina USA"},{"name":"Department of Health and Exercise Science Wake Forest University Winston Salem North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Debra I.","family":"Diz","sequence":"additional","affiliation":[{"name":"Cardiovascular Sciences Center Wake Forest School of Medicine Winston Salem North Carolina USA"},{"name":"Department of Surgery\u2010Hypertension and Vascular Research Wake Forest School of Medicine Winston Salem North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark C.","family":"Chappell","sequence":"additional","affiliation":[{"name":"Cardiovascular Sciences Center Wake Forest School of Medicine Winston Salem North Carolina USA"},{"name":"Department of Surgery\u2010Hypertension and Vascular Research Wake Forest School of Medicine Winston Salem North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa K.","family":"Washburn","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Wake Forest School of Medicine and Brenner Children's Hospital Winston Salem North Carolina USA"},{"name":"Cardiovascular Sciences Center Wake Forest School of Medicine Winston Salem North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,5,31]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000558"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)61766-8"},{"issue":"3","key":"e_1_2_9_4_1","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1053\/j.ajkd.2019.01.001","article-title":"US Renal Data System 2018 annual data report: epidemiology of kidney disease in the United States","volume":"73","author":"Saran R","year":"2019","journal-title":"Am J Kidney Dis"},{"issue":"6","key":"e_1_2_9_5_1","first-page":"e13","article-title":"2017 ACC\/AHA\/AAPA\/ABC\/ACPM\/AGS\/APhA\/ASH\/ASPC\/NMA\/PCNA Guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology\/American Heart Association Task Force on Clinical Practice Guidelines","volume":"71","author":"Whelton PK","year":"2018","journal-title":"Hypertension"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000157171.04054.30"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.022484299"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/36285"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2369-13-155"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.118.11176"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.02700313"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2015.08.004"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1159\/000316703"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000251865.35728.2f"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12913"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)60820-4"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwq440"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-12-0476"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1097\/HJH.0000000000001801"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2018.09.058"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/pr.2016.179"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1542\/pir.16-9-354"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1550-8528.1998.tb00690.x"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.289.19.2560"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2016.03.004"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1114248"},{"key":"e_1_2_9_27_1","volume-title":"Methods of dealing with values below the limit of detection using SAS","author":"Croghan C","year":"2003"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2288-8-70"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1042\/CS20171550"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2010-2357"},{"issue":"5","key":"e_1_2_9_31_1","first-page":"1998","article-title":"Clinic significance of markedly decreased \u03b1\u2010klotho in women with preeclampsia","volume":"8","author":"Fan C","year":"2016","journal-title":"Am J Transl Res"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2018.00797"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2018.05.056"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.4238\/2015.November.30.22"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.116.07709"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajh\/hpw062"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00618.2015"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2012.370"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1998.8943"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2013101033"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2010.08.050"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.118.11397"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1385\/ENDO:18:3:239"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1097\/HJH.0000000000000251"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature25451"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2010121251"}],"container-title":["The Journal of Clinical Hypertension"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjch.13897","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jch.13897","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/jch.13897","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jch.13897","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T09:29:00Z","timestamp":1693992540000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jch.13897"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5,31]]},"references-count":45,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2020,6]]}},"alternative-id":["10.1111\/jch.13897"],"URL":"https:\/\/doi.org\/10.1111\/jch.13897","archive":["Portico"],"relation":{},"ISSN":["1524-6175","1751-7176"],"issn-type":[{"value":"1524-6175","type":"print"},{"value":"1751-7176","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,5,31]]},"assertion":[{"value":"2020-02-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-04-20","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-05-31","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}