{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T00:39:52Z","timestamp":1792629592793,"version":"4.5.0"},"reference-count":39,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2017,7,6]],"date-time":"2017-07-06T00:00:00Z","timestamp":1499299200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Lupus"],"published-print":{"date-parts":[[2018,2]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Pulsed cyclophosphamide or mycophenolate mofetil for lupus nephritis has limited efficacy. We previously reported a case of mixed-class IV\u2009+\u2009V lupus nephritis successfully treated with cyclophosphamide and tacrolimus. This study assessed the efficacy and safety of multitarget therapy with cyclophosphamide and tacrolimus for the treatment of lupus nephritis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In a prospective, single-arm, open label pilot study, we recruited 15 patients aged 18\u201364 years with active lupus nephritis who met the American College of Rheumatology criteria for a diagnosis of systemic lupus erythematosus (1997). The treatment protocol was a starting dose of prednisolone of 0.6\u22121.0\u2009mg\/kg\/day for 2 weeks and then tapered to a maintenance dose, intravenous cyclophosphamide (500\u2009mg biweekly for 3 months) and tacrolimus (3.0\u2009mg\/day). Tacrolimus was continued as maintenance therapy. Complete remission was defined as a spot urine protein\/creatinine ratio of\u2009&lt;\u20090.5\u2009g\/gCr with no active urine casts and a serum creatinine level that was either normal or within 30% of a previously abnormal baseline level. We retrospectively compared results for the study patients with those of 18 historical controls conventionally treated with cyclophosphamide and prednisolone.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>At baseline, the mean patient age was 41.5\u2009\u00b1\u200914.6 years (male:female ratio 2:13), urine protein\/creatinine ratio 3.9\u2009\u00b1\u20092.3\u2009g\/gCr and serum creatinine 84.6\u2009\u00b1\u200934.6\u2009\u00b5mol\/L. Lupus nephritis classifications included classes IV ( n\u2009=\u20098), III\u2009+\u2009V ( n\u2009=\u20091), IV\u2009+\u2009V ( n\u2009=\u20095) and unclassified ( n\u2009=\u20091). Eleven patients completed the treatment protocol and four withdrew. At 6 months, 12 of 15 (80.0%) had achieved complete remission using intention-to-treat analysis, significantly more than historical controls (seven of 18 patients, 38.9%). A transient increase in serum creatinine and gastric symptoms occurred in three cases. One patient withdrew due to cytomegalovirus antigenemia and severe diabetes, and one patient died of thrombotic microangiopathy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Multitarget therapy with cyclophosphamide and tacrolimus can be a therapeutic option for lupus nephritis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical trials registration<\/jats:title>\n                    <jats:p>Combination therapy of tacrolimus and intravenous cyclophosphamide for remission induction of lupus nephritis, UMIN: 000004893, URL: https:\/\/upload.umin.ac.jp\/cgi-open-bin\/ctr\/ctr.cgi?function=brows&amp;action=brows&amp;type=summary&amp;recptno=R000005830&amp;language=E . Date of registration: 18 January 2011.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/0961203317719148","type":"journal-article","created":{"date-parts":[[2017,12,27]],"date-time":"2017-12-27T01:13:44Z","timestamp":1514337224000},"page":"273-282","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":21,"title":["Efficacy and safety of multitarget therapy with cyclophosphamide and tacrolimus for lupus nephritis: a prospective, single-arm, single-centre, open label pilot study in Japan"],"prefix":"10.1177","volume":"27","author":[{"given":"R","family":"Sakai","sequence":"first","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Saitama Medical University, Saitama, Japan"},{"name":"Department of Microbiology and Immunology, Keio University, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T","family":"Kurasawa","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Saitama Medical University, Saitama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E","family":"Nishi","sequence":"additional","affiliation":[{"name":"Institute of Rheumatology, Zenjinkai Shimin-no-Mori Hospital, Miyazaki, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T","family":"Kondo","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Saitama Medical University, Saitama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y","family":"Okada","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Saitama Medical University, Saitama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Shibata","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Saitama Medical University, Saitama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"Nishimura","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Saitama Medical University, Saitama, Japan"},{"name":"Division of Rheumatology, Japan Community Health Care Organization, Saitama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"Chino","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Saitama Medical University, Saitama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Okuyama","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Saitama Medical University, Saitama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H","family":"Takei","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Saitama Medical University, Saitama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H","family":"Nagasawa","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Saitama Medical University, Saitama, Japan"},{"name":"Nagasawa Clinic, Saitama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"Amano","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Saitama Medical University, Saitama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2017,7,6]]},"reference":[{"key":"bibr1-0961203317719148","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2008101028"},{"key":"bibr2-0961203317719148","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa043731"},{"key":"bibr3-0961203317719148","doi-asserted-by":"publisher","DOI":"10.1177\/0961203308089428"},{"key":"bibr4-0961203317719148","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfr484"},{"key":"bibr5-0961203317719148","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(199805)41:5<831::AID-ART9>3.0.CO;2-1"},{"key":"bibr6-0961203317719148","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-91-2-221"},{"key":"bibr7-0961203317719148","doi-asserted-by":"publisher","DOI":"10.1016\/j.rdc.2014.04.005"},{"key":"bibr8-0961203317719148","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2007121272"},{"key":"bibr9-0961203317719148","doi-asserted-by":"publisher","DOI":"10.7326\/M14-1030"},{"key":"bibr10-0961203317719148","doi-asserted-by":"publisher","DOI":"10.3109\/14397595.2013.844397"},{"key":"bibr11-0961203317719148","doi-asserted-by":"publisher","DOI":"10.1177\/0961203314528553"},{"key":"bibr12-0961203317719148","doi-asserted-by":"publisher","DOI":"10.1177\/0961203312458468"},{"key":"bibr13-0961203317719148","doi-asserted-by":"publisher","DOI":"10.1007\/s10157-012-0632-4"},{"key":"bibr14-0961203317719148","doi-asserted-by":"publisher","DOI":"10.1177\/0961203310365714"},{"key":"bibr15-0961203317719148","doi-asserted-by":"publisher","DOI":"10.1177\/0961203313502864"},{"key":"bibr16-0961203317719148","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfq322"},{"key":"bibr17-0961203317719148","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2012-202844"},{"key":"bibr18-0961203317719148","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2016040415"},{"key":"bibr19-0961203317719148","doi-asserted-by":"publisher","DOI":"10.3109\/14397595.2015.1031444"},{"key":"bibr20-0961203317719148","doi-asserted-by":"publisher","DOI":"10.3109\/s10165-012-0645-6"},{"key":"bibr21-0961203317719148","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(92)92292-N"},{"key":"bibr22-0961203317719148","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2012-201940"},{"key":"bibr23-0961203317719148","doi-asserted-by":"publisher","DOI":"10.2169\/internalmedicine.52.9366"},{"key":"bibr24-0961203317719148","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780400928"},{"key":"bibr25-0961203317719148","doi-asserted-by":"publisher","DOI":"10.1002\/art.10461"},{"key":"bibr26-0961203317719148","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780350606"},{"key":"bibr27-0961203317719148","doi-asserted-by":"publisher","DOI":"10.1097\/01.ASN.0000108969.21691.5D"},{"key":"bibr28-0961203317719148","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(83)90338-8"},{"key":"bibr29-0961203317719148","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfw068"},{"key":"bibr30-0961203317719148","doi-asserted-by":"publisher","DOI":"10.1002\/art.21263"},{"key":"bibr31-0961203317719148","doi-asserted-by":"publisher","DOI":"10.1016\/j.semarthrit.2011.05.008"},{"key":"bibr32-0961203317719148","doi-asserted-by":"publisher","DOI":"10.1002\/anr.1780320911"},{"key":"bibr33-0961203317719148","doi-asserted-by":"publisher","DOI":"10.1053\/ajkd.2000.17690"},{"key":"bibr34-0961203317719148","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kep346"},{"key":"bibr35-0961203317719148","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/ken335"},{"key":"bibr36-0961203317719148","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2013-204385"},{"key":"bibr37-0961203317719148","doi-asserted-by":"publisher","DOI":"10.3109\/14397595.2015.1060665"},{"key":"bibr38-0961203317719148","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/ket462"},{"key":"bibr39-0961203317719148","doi-asserted-by":"publisher","DOI":"10.1002\/acr.22574"}],"container-title":["Lupus"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0961203317719148","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/0961203317719148","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0961203317719148","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T23:18:26Z","timestamp":1777677506000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/0961203317719148"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,7,6]]},"references-count":39,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2018,2]]}},"alternative-id":["10.1177\/0961203317719148"],"URL":"https:\/\/doi.org\/10.1177\/0961203317719148","relation":{},"ISSN":["0961-2033","1477-0962"],"issn-type":[{"value":"0961-2033","type":"print"},{"value":"1477-0962","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,7,6]]}}}