{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T09:32:03Z","timestamp":1778664723635,"version":"3.51.4"},"reference-count":33,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2019,12,25]],"date-time":"2019-12-25T00:00:00Z","timestamp":1577232000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP19fk0210040"],"award-info":[{"award-number":["JP19fk0210040"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["16H06389"],"award-info":[{"award-number":["16H06389"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Non-alcoholic fatty liver disease (NAFLD) is associated with chronic kidney disease (CKD). The aim of this retrospective study was to determine the risk factors for progression of CKD in patients with biopsy-proven NAFLD including patatin-like phospholipase domain containing 3 (PNPLA3) polymorphism. A total of 344 patients with biopsy-proven NAFLD were enrolled consecutively in this study. Multivariate analysis identified males (odds ratio (OR) 5.46), age (per 1 year, OR 1.07), and FIB-4 index (\u22651.30, OR 3.85) as factors associated with CKD. Of the 154 patients with a baseline estimated glomerular filtration rate (eGFR) \u226560 mL\/min, 30 had a deterioration in CKD stage and 15 developed CKD after 3 years. Multivariate analysis identified diabetes mellitus (OR 2.44) as a risk factor for deterioration in CKD stage, while diabetes mellitus (OR 21.54) and baseline eGFR (per 1 mL\/min OR 0.88) were risk factors for development of CKD. PNPLA3 did not affect the change in eGFR. In NAFLD patients, a high FIB-4 index was associated with CKD to increases in the index linked to reductions in eGFR. In order to prevent development of CKD, an appropriate therapy focusing on renal function is needed for NAFLD patients, especially those with diabetes.<\/jats:p>","DOI":"10.3390\/ijms21010171","type":"journal-article","created":{"date-parts":[[2019,12,25]],"date-time":"2019-12-25T11:07:48Z","timestamp":1577272068000},"page":"171","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["FIB-4 Index and Diabetes Mellitus Are Associated with Chronic Kidney Disease in Japanese Patients with Non-Alcoholic Fatty Liver Disease"],"prefix":"10.3390","volume":"21","author":[{"given":"Yuya","family":"Seko","sequence":"first","affiliation":[{"name":"Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto 6028566, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kohta","family":"Yano","sequence":"additional","affiliation":[{"name":"Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto 6028566, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aya","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto 6028566, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shinya","family":"Okishio","sequence":"additional","affiliation":[{"name":"Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto 6028566, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seita","family":"Kataoka","sequence":"additional","affiliation":[{"name":"Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto 6028566, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keiichiroh","family":"Okuda","sequence":"additional","affiliation":[{"name":"Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto 6028566, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naoki","family":"Mizuno","sequence":"additional","affiliation":[{"name":"Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto 6028566, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masashi","family":"Takemura","sequence":"additional","affiliation":[{"name":"Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto 6028566, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroyoshi","family":"Taketani","sequence":"additional","affiliation":[{"name":"Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto 6028566, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Atsushi","family":"Umemura","sequence":"additional","affiliation":[{"name":"Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto 6028566, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taichiro","family":"Nishikawa","sequence":"additional","affiliation":[{"name":"Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto 6028566, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kanji","family":"Yamaguchi","sequence":"additional","affiliation":[{"name":"Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto 6028566, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michihisa","family":"Moriguchi","sequence":"additional","affiliation":[{"name":"Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto 6028566, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2390-3400","authenticated-orcid":false,"given":"Takeshi","family":"Okanoue","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Saiseikai Suita Hospital, Osaka 5640013, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshito","family":"Itoh","sequence":"additional","affiliation":[{"name":"Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto 6028566, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,12,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1002\/hep.28431","article-title":"Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes","volume":"64","author":"Younossi","year":"2016","journal-title":"Hepatology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1007\/s00535-015-1050-7","article-title":"Japanese Society of Gastroenterology; Japan Society of Hepatology. Evidence-based clinical practice guidelines for nonalcoholic fatty liver disease\/nonalcoholic steatohepatitis","volume":"50","author":"Watanabe","year":"2015","journal-title":"J. Gastroenterol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2005","DOI":"10.1002\/hep.25762","article-title":"The diagnosis and management of non-alcoholic fatty liver disease: Practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association","volume":"55","author":"Chalasani","year":"2012","journal-title":"Hepatology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"S47","DOI":"10.1016\/j.jhep.2014.12.012","article-title":"NAFLD: A multisystem disease","volume":"62","author":"Byrne","year":"2015","journal-title":"J. Hepatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1038\/nrneph.2017.16","article-title":"Non-alcoholic fatty liver disease: An emerging driving force in chronic kidney disease","volume":"13","author":"Targher","year":"2017","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1097\/MEG.0000000000000582","article-title":"Is nonalcoholic fatty liver disease a risk factor for chronic kidney disease?","volume":"28","author":"Ozturk","year":"2016","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Marcuccilli, M., and Chonchol, M. (2016). NAFLD and chronic kidney disease. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17040562"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/j.jhep.2016.04.005","article-title":"Non-alcoholic fatty liver disease and cardiovascular risk: Pathophysiological mechanisms and implications","volume":"65","author":"Francque","year":"2016","journal-title":"J. Hepatol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.metabol.2017.11.003","article-title":"Nonalcoholic fatty liver disease increases risk of incident chronic kidney disease: A systematic review and meta-analysis","volume":"79","author":"Mantovani","year":"2018","journal-title":"Metabolism"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.2169\/internalmedicine.50.5043","article-title":"The development of chronic kidney disease in Japanese patients with non-alcoholic fatty liver disease","volume":"50","author":"Arase","year":"2011","journal-title":"Intern. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1564","DOI":"10.1681\/ASN.2007101155","article-title":"Increased risk of CKD among type 2 diabetics with nonalcoholic fatty liver disease","volume":"19","author":"Targher","year":"2008","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1729","DOI":"10.2337\/dc13-2704","article-title":"Nonalcoholic fatty liver disease is independently associated with an increased incidence of chronic kidney disease in patients with type 1 diabetes","volume":"37","author":"Targher","year":"2014","journal-title":"Diabetes Care"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1016\/j.metabol.2007.11.022","article-title":"Nonalcoholic fatty liver disease predicts chronic kidney disease in nonhypertensive and nondiabetic Korean men","volume":"57","author":"Chang","year":"2008","journal-title":"Metabolism"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1274","DOI":"10.1016\/j.jhep.2017.08.024","article-title":"Development of chronic kidney disease in patients with non-alcoholic fatty liver disease: A cohort study","volume":"67","author":"Sinn","year":"2017","journal-title":"J. Hepatol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1016\/j.metabol.2010.07.022","article-title":"Nonalcoholic steatohepatitis and increased risk of chronic kidney disease","volume":"60","author":"Yasui","year":"2011","journal-title":"Metabolism"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1053\/j.ajkd.2018.02.362","article-title":"Obesity, Metabolic Abnormality, and Progression of CKD","volume":"72","author":"Yun","year":"2018","journal-title":"Am. J. Kidney Dis."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Kittiskulnam, P., Thokanit, N.S., Katavetin, P., Susanthitaphong, P., Srisawat, N., Praditpornsilpa, K., and Eiam-Ong, S. (2018). The magnitude of obesity and metabolic syndrome among diabetic chronic kidney disease population: A nationwide study. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0196332"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"578","DOI":"10.2215\/CJN.08980914","article-title":"Metabolically healthy obesity and risk of incident CKD","volume":"10","author":"Hashimoto","year":"2015","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1038\/sj.ki.5002017","article-title":"Risk factors for chronic kidney disease in a community-based population: A 10-year follow-up study","volume":"71","author":"Yamagata","year":"2007","journal-title":"Kidney Int."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2166","DOI":"10.2215\/CJN.05050610","article-title":"Relationship between kidney function and liver histology in subjects with nonalcoholic steatohepatitis","volume":"5","author":"Targher","year":"2010","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1016\/j.metabol.2009.12.012","article-title":"Microalbuminuria in nondiabetic patients with nonalcoholic fatty liver disease: Association with liver fibrosis","volume":"59","author":"Yilmaz","year":"2010","journal-title":"Metabolism"},{"key":"ref_22","unstructured":"Chen, P.C., Kao, W.Y., Cheng, Y.L., Wang, Y.J., Hou, M.C., Wu, J.C., and Su, C.W. (2019). The correlation between fatty liver disease and chronic kidney disease. J. Formos. Med. Assoc."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1291\/hypres.31.433","article-title":"Slower decline of glomerular filtration rate in the Japanese general population: A longitudinal 10-year follow-up study","volume":"31","author":"Imai","year":"2008","journal-title":"Hypertens. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1971","DOI":"10.1016\/j.biochi.2013.07.017","article-title":"Ectopic lipid accumulation: A potential cause for metabolic disturbances and a contributor to the alteration of kidney function","volume":"95","author":"Alix","year":"2013","journal-title":"Biochimie"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1681\/ASN.2009080820","article-title":"Mechanisms linking obesity, chronic kidney disease, and fatty liver disease: The roles of fetuin-A, adiponectin, and AMPK","volume":"21","author":"Ix","year":"2010","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1161\/HYPERTENSIONAHA.111.175315","article-title":"Fatty kidney, hypertension, and chronic kidney disease: The Framingham Heart Study","volume":"58","author":"Foster","year":"2011","journal-title":"Hypertension"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3803\/EnM.2014.29.1.1","article-title":"Ectopic fat assessment focusing on cardiometabolic and renal risk","volume":"29","author":"Lim","year":"2014","journal-title":"Endocrinol. Metab."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Sun, D.Q., Zheng, K.I., Xu, G., Ma, H.L., Zhang, H.Y., Pan, X.Y., and Chen, Y.P. (2019). PNPLA3 rs738409 is associated with renal glomerular and tubular injury in NAFLD patients with persistently normal ALT levels. Liver Int., 13.","DOI":"10.1111\/liv.14251"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2473","DOI":"10.1056\/NEJMra054415","article-title":"Assessing kidney function\u2013measured and estimated glomerular filtration rate","volume":"354","author":"Stevens","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1053\/j.ajkd.2008.12.034","article-title":"Collaborators developing the Japanese equation for estimated GFR. Revised equations for estimated GFR from serum creatinine in Japan","volume":"53","author":"Matsuo","year":"2009","journal-title":"Am. J. Kidney Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1016\/S0016-5085(99)70506-8","article-title":"Nonalcoholic fatty liver diseases: A spectrum of clinical and pathological severity","volume":"116","author":"Matteoni","year":"1999","journal-title":"Gastroenterology"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1002\/hep.20701","article-title":"Design and validation of a histological scoring system for nonalcoholic fatty liver disease","volume":"41","author":"Kleiner","year":"2005","journal-title":"Hepatology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2467","DOI":"10.1111\/j.1572-0241.1999.01377.x","article-title":"Nonalcoholic steatohepatitis: A proposal for grading and staging the histological lesions","volume":"94","author":"Brunt","year":"1999","journal-title":"Am. J. Gastroenterol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/1\/171\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:45:43Z","timestamp":1760190343000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/1\/171"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12,25]]},"references-count":33,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,1]]}},"alternative-id":["ijms21010171"],"URL":"https:\/\/doi.org\/10.3390\/ijms21010171","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,12,25]]}}}