{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T20:30:12Z","timestamp":1740169812683,"version":"3.37.3"},"reference-count":21,"publisher":"Wiley","license":[{"start":{"date-parts":[[2019,11,11]],"date-time":"2019-11-11T00:00:00Z","timestamp":1573430400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Zhejiang Provincial Health Commission","award":["2019309067","81671594","81571591"],"award-info":[{"award-number":["2019309067","81671594","81571591"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2019309067","81671594","81571591"],"award-info":[{"award-number":["2019309067","81671594","81571591"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2019309067","81671594","81571591"],"award-info":[{"award-number":["2019309067","81671594","81571591"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2019309067","81671594","81571591"],"award-info":[{"award-number":["2019309067","81671594","81571591"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["BioMed Research International"],"published-print":{"date-parts":[[2019,11,11]]},"abstract":"<jats:p>Human epididymis protein 4 (HE4) is an available tumor biomarker mainly for detecting ovarian cancer. However, it is unknown whether it can be a novel indicator for diagnosis of diabetic kidney disease (DKD). The aim of this study was to investigate the possibility of serum HE4 as a novel biomarker for DKD in patients with type 2 diabetes mellitus (T2DM). We enrolled 236 patients with T2DM and 82 healthy individuals. Serum HE4 was detected by ARCHITECT i2000 and compared between T2DM patients and healthy controls. The relationships between various variables and HE4 were analyzed by univariate or multivariate linear regression analyses. The receiver operating characteristic (ROC) curve was constructed to assess the diagnostic performance of HE4 for DKD. The association between HE4 and DKD was analyzed by logistic regression analysis. The serum HE4 level was significantly increased in T2DM patients (median, interquartile range (IQR), 69.7, 46.5\u2013153.9, pM) compared with healthy control (median, IQR, 40.3 33.2\u201346.3, pM) (<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M1\"><mml:mrow><mml:mi>P<\/mml:mi><mml:mo>&lt;<\/mml:mo><mml:mn>0.001<\/mml:mn><\/mml:mrow><\/mml:math>). Furthermore, it was higher in those with DKD (median, IQR, 211.1, 141.6\u2013367.4, pM) than those without DKD (median, IQR, 55.5, 42.7\u201379.6, pM) (<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M2\"><mml:mrow><mml:mi>P<\/mml:mi><mml:mo>&lt;<\/mml:mo><mml:mn>0.001<\/mml:mn><\/mml:mrow><\/mml:math>). The multivariable analysis showed that age, eGFR, HDL, CRP, and urea significantly independently correlated with HE4 level, while other variables did not. The ROC curve showed that the diagnostic performance of serum HE4 for DKD with 82.9\u2009pM as the optimal cutoff value was good (AUC\u2009=\u20090.917, 95% CI: 0.872\u20130.961, <mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M3\"><mml:mrow><mml:mi>P<\/mml:mi><mml:mo>&lt;<\/mml:mo><mml:mn>0.001<\/mml:mn><\/mml:mrow><\/mml:math>, with a sensitivity and specificity of 92.1% and 76.9%, respectively) in T2DM patients. Multivariable logistic regression analysis showed that increased HE4 level was a significant, independent risk factor for DKD (OR, 95% CI, 57.7, 3.0\u20131112.9, <mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M4\"><mml:mrow><mml:mi>P<\/mml:mi><mml:mo>&lt;<\/mml:mo><mml:mn>0.001<\/mml:mn><\/mml:mrow><\/mml:math>) after adjusting for factors associated with HE4. Increased serum HE4 level is associated with decreased renal function and increased risks of DKD in patients with DM. It displays a good diagnostic value for DKD.<\/jats:p>","DOI":"10.1155\/2019\/4831459","type":"journal-article","created":{"date-parts":[[2019,11,11]],"date-time":"2019-11-11T18:33:39Z","timestamp":1573497219000},"page":"1-6","source":"Crossref","is-referenced-by-count":4,"title":["Serum Human Epididymis Protein 4 is Associated with Renal Function and Diabetic Kidney Disease in Patients with Type 2 Diabetes Mellitus"],"prefix":"10.1155","volume":"2019","author":[{"given":"Miaomiao","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, Huangyan Hospital Affiliated to Wenzhou Medical University, Taizhou First People\u2019s Hospital, Wenzhou, Zhejiang, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bing","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Huangyan Hospital Affiliated to Wenzhou Medical University, Taizhou First People\u2019s Hospital, Wenzhou, Zhejiang, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Huangyan Hospital Affiliated to Wenzhou Medical University, Taizhou First People\u2019s Hospital, Wenzhou, Zhejiang, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Diagnostics, Shanghai Changzheng Hospital, Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7545-642X","authenticated-orcid":true,"given":"Zaixing","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Huangyan Hospital Affiliated to Wenzhou Medical University, Taizhou First People\u2019s Hospital, Wenzhou, Zhejiang, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","reference":[{"key":"1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(17)30058-2"},{"key":"2","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2013.10.048"},{"key":"3","doi-asserted-by":"publisher","DOI":"10.1007\/s11892-019-1133-6"},{"key":"4","doi-asserted-by":"publisher","DOI":"10.1038\/s41581-018-0001-y"},{"key":"5","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod45.2.350"},{"key":"6","doi-asserted-by":"publisher","DOI":"10.1080\/14737140.2017.1360138"},{"key":"7","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.epi-14-0447"},{"key":"8","doi-asserted-by":"publisher","DOI":"10.1002\/jcla.21954"},{"key":"9","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2018.04.048"},{"key":"10","doi-asserted-by":"publisher","DOI":"10.1258\/acb.2011.011258"},{"key":"11","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.11682"},{"key":"12","doi-asserted-by":"publisher","DOI":"10.1093\/labmed\/lmx036"},{"key":"13","doi-asserted-by":"publisher","DOI":"10.1007\/s11255-018-1930-x"},{"key":"14","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2012.07.005"},{"key":"15","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2013.243"},{"key":"16","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-150-9-200905050-00006"},{"key":"17","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2014.08.001"},{"key":"18","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardfail.2016.05.002"},{"key":"19","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinbiochem.2013.08.019"},{"key":"20","doi-asserted-by":"publisher","DOI":"10.1016\/j.chest.2016.04.006"},{"key":"21","doi-asserted-by":"publisher","DOI":"10.2337\/dc16-1246"}],"container-title":["BioMed Research International"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/downloads.hindawi.com\/journals\/bmri\/2019\/4831459.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/bmri\/2019\/4831459.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/bmri\/2019\/4831459.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,11,11]],"date-time":"2019-11-11T18:33:44Z","timestamp":1573497224000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.hindawi.com\/journals\/bmri\/2019\/4831459\/"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11,11]]},"references-count":21,"alternative-id":["4831459","4831459"],"URL":"https:\/\/doi.org\/10.1155\/2019\/4831459","relation":{},"ISSN":["2314-6133","2314-6141"],"issn-type":[{"type":"print","value":"2314-6133"},{"type":"electronic","value":"2314-6141"}],"subject":[],"published":{"date-parts":[[2019,11,11]]}}}