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To date, few studies have been published using multiple combination therapy of immunosuppressive reagents for children with calcineurin inhibitor\u2010resistant or \u2010intolerant nephrotic syndrome.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Eighteen consecutive children with steroid\u2010 and tacrolimus (TAC)\u2010resistant (<jats:italic>n<\/jats:italic>\u2009=\u200910) or TAC\u2010sensitive but frequent relapsing nephrotic syndrome (<jats:italic>n<\/jats:italic>\u2009=\u20098) were randomly recruited in the present study. All of them received further triple\u2010combination therapy by cyclophosphamide (CTX, <jats:italic>n<\/jats:italic>\u2009=\u20096), mycophenolate mofetil (MMF, <jats:italic>n<\/jats:italic>\u2009=\u20095) or leflunomide (LEF, <jats:italic>n<\/jats:italic>\u2009=\u20097). Their clinical data were collected and efficacy of triple\u2010combination therapy was evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared with previous double\u2010combination therapy of prednisone (Pre) and TAC, the short\u2010term <jats:italic>remission<\/jats:italic> rate in all 18 patients was significantly improved after the triple\u2010combination therapy, while the frequent relapse rate in the following 12\u2009months was also significantly decreased. Among three different subgroups with CTX, MMF or LEF therapy, no significant difference was found in short\u2010term remission rate and the relapse rate within 1\u2009year follow up by Kaplan\u2013Meier plot.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Triple\u2010combination therapy with Pre\u2009+\u2009TAC\u2009+\u2009CTX\/MMF\/LEF is effective for short\u2010term response and 1\u2009year remission, without significant additional side\u2010effects seen in children with steroid\u2010resistant and tacrolimus\u2010resistant or tacrolimus\u2010sensitive but frequently relapsing nephrotic syndrome. Further study for evaluating long\u2010term efficacy and safety of triple\u2010combination therapy with Pre\u2009+\u2009TAC\u2009+\u2009CTX\/MMF\/LEF would be necessary for these patients.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nep.12351","type":"journal-article","created":{"date-parts":[[2014,10,14]],"date-time":"2014-10-14T07:47:37Z","timestamp":1413272857000},"page":"18-24","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Triple immunosuppressive therapy in steroid\u2010resistant nephrotic syndrome children with tacrolimus resistance or tacrolimus sensitivity but frequently relapsing"],"prefix":"10.1111","volume":"20","author":[{"given":"Boying","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Nephrology The Children's Hospital of Zhejiang University School of Medicine  Hangzhou China"},{"name":"Department of Pediatrics Ningbo Yinzhou People's Hospital  Ningbo China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianhua","family":"Mao","sequence":"additional","affiliation":[{"name":"Department of Nephrology The Children's Hospital of Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huijun","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Nephrology The Children's Hospital of Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haidong","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Nephrology The Children's Hospital of Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingjing","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Nephrology The Children's Hospital of Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aimin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Nephrology The Children's Hospital of Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weizhong","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Nephrology The Children's Hospital of Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiang","family":"Shu","sequence":"additional","affiliation":[{"name":"Department of Nephrology The Children's Hospital of Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lizhong","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Nephrology The Children's Hospital of Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,12,23]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00467-005-2097-0"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1981.209"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00467-012-2304-8"},{"key":"e_1_2_6_5_1","first-page":"72","article-title":"Guide interpretation for children with steroid resistant nephrotic syndrome","volume":"48","author":"Xia ZK","year":"2010","journal-title":"Chin. 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