{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T01:43:34Z","timestamp":1791855814521,"version":"4.3.4"},"reference-count":38,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","funder":[{"DOI":"10.13039\/501100004948","name":"Astellas Pharma","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004948","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["JASN"],"published-print":{"date-parts":[[2021,1]]},"abstract":"\n Significance Statement<\/jats:title>\n Steroid resistance, relapse, and side effects are common issues in use of high-dose steroids as first-line treatment for adult minimal change nephrotic syndrome. Tacrolimus is used as a steroid-sparing immunosuppressant to reduce adverse effects of long-term or repeated steroid treatment, but no large-scale randomized study has compared combined tacrolimus and low-dose steroid with high-dose steroid in treating minimal change nephrotic syndrome in adults. In this open-label randomized trial, the authors found that treatment with tacrolimus plus low-dose steroid was noninferior to high-dose steroid for complete remission at 8 weeks, and that treatment with a maintenance dose of tacrolimus during steroid tapering reduced the relapse rate, with no clinically-relevant safety differences. This indicates that tacrolimus is an effective alternative to high-dose steroids in this disease, although investigation into long-term safety is warranted.<\/jats:p>\n <\/jats:sec>\n \n Background<\/jats:title>\n Tacrolimus is used as a steroid-sparing immunosuppressant in adults with minimal change nephrotic syndrome. However, combined treatment with tacrolimus and low-dose steroid has not been compared with high-dose steroid for induction of clinical remission in a large-scale randomized study.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n In this 24-week open-label noninferiority study, we randomized 144 adults with minimal change nephrotic syndrome to receive 0.05 mg\/kg twice-daily tacrolimus plus once-daily 0.5 mg\/kg prednisolone, or once-daily 1 mg\/kg prednisolone alone, for up to 8 weeks or until achieving complete remission. Two weeks after complete remission, we tapered the steroid to a maintenance dose of 5\u20137.5 mg\/d in both groups until 24 weeks after study drug initiation. The primary end point was complete remission within 8 weeks (urine protein: creatinine ratio <0.2 g\/g). Secondary end points included time until remission and relapse rates (proteinuria and urine protein: creatinine ratio >3.0 g\/g) after complete remission to within 24 weeks of study drug initiation.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Complete remission within 8 weeks occurred in 53 of 67 patients (79.1%) receiving tacrolimus and low-dose steroid and 53 of 69 patients (76.8%) receiving high-dose steroid; this difference demonstrated noninferiority, with an upper confidence limit below the predefined threshold (20%) in both intent-to-treat (11.6%) and per-protocol (17.0%) analyses. Groups did not significantly differ in time until remission. Significantly fewer patients relapsed on maintenance tacrolimus (3\u20138 ng\/ml) plus tapered steroid versus tapered steroid alone (5.7% versus 22.6%, respectively;\n P<\/jats:italic>\n =0.01). There were no clinically relevant safety differences.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n Combined tacrolimus and low-dose steroid was noninferior to high-dose steroid for complete remission induction in adults with minimal change nephrotic syndrome. Relapse rates were significantly lower with maintenance tacrolimus and steroid compared with steroid alone. No clinically-relevant differences in safety findings were observed.<\/jats:p>\n <\/jats:sec>","DOI":"10.1681\/asn.2019050546","type":"journal-article","created":{"date-parts":[[2020,11,9]],"date-time":"2020-11-09T21:55:18Z","timestamp":1604958918000},"page":"199-210","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":34,"title":["Comparison of the Efficacy and Safety of Tacrolimus and Low-Dose Corticosteroid with High-Dose Corticosteroid for Minimal Change Nephrotic Syndrome in Adults"],"prefix":"10.1681","volume":"32","clinical-trial-number":[{"clinical-trial-number":"nct01763580","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Ho Jun","family":"Chin","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea"},{"name":"Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong-Wan","family":"Chae","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong Chul","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4015-0284","authenticated-orcid":false,"given":"Won Suk","family":"An","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Dong-A University College of Medicine, Busan, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ChunGyoo","family":"Ihm","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Kyunghee University Medical Center, Seoul, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong-Chan","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, St Vincent Hospital, Suwon, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5034-0527","authenticated-orcid":false,"given":"Sung Gyun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Hallym University Sacred Heart Hospital, Anyang, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong-Lim","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong-Soo","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, The Catholic University of Korea, Seoul St. Mary\u2019s Hospital, Seoul, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoon-Goo","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Medicine, Samsung Medical Centre, Sungkyunkwan University School of Medicine, Seoul, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ho Seok","family":"Koo","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Inje University Seoul Paik Hospital, Seoul, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung Eun","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Medicine, Samsung Medical Centre, Sungkyunkwan University School of Medicine, Seoul, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kang Wook","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Chungnam National University Hospital, Daejeon, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9429-9602","authenticated-orcid":false,"given":"Jieun","family":"Oh","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Kangdong Sacred Heart Hospital, Seoul, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8737-0084","authenticated-orcid":false,"given":"Jung Hwan","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Konkuk University Medical Center, Seoul, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongsi","family":"Jiang","sequence":"additional","affiliation":[{"name":"Medical Affairs Asia Oceania, Astellas Pharma Singapore Pte. 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