title: Tacrolimus versus intravenous pulse cyclophosphamide therapy in Chinese adults with steroid-resistant idiopathic minimal change nephropathy: a multicenter, open-label, nonrandomized cohort trial.
abstract: BACKGROUND
  The treatment of steroid-resistant minimal change nephropathy (SR-MCN) in adults remains a challenge to nephrologists. Although immunosuppressants such as cyclophosphamide (CTX), chlorambucil, and cyclosporin A have been used in these patients, their use has been limited by low remission rates and severe adverse effects. Alternative immunosuppressive treatments for SR-MCN are therefore needed.
  
  
  OBJECTIVE
  The aim of this study was to compare the efficacy of tacrolimus (TAC) with that of intravenous (IV) pulse CTX therapy in the management of SR-MCN and to assess the tolerability of those treatments.
  
  
  METHODS
  This was a nonrandomized, case-matched trial in Chinese adults with SR-MCN. Patients were self-assigned to either: (1) combination therapy with prednisone and oral TAC; or (2) combination therapy with prednisone and IV CTX. TAC was initiated at 0.05 mg/kg/d and was adjusted to maintain a trough blood level of 5 to 10 ng/mL for 1 year. CTX was initiated at 1 g/1.73 m(2) for a total dosage of 10 g/1.73 m(2) over 1 year. In both groups, oral prednisone was initiated at 0.5 mg/kg/d for 3 months but was tapered off to complete cessation by 6 months.
  
  
  RESULTS
  A total of 37 patients were enrolled (21 in the TAC group; 16 in the CTX group), of whom 33 (19 in the TAC group; 14 in the CTX group) completed the study. There were no significant difference in baseline demographic characteristics between the two treatment groups (The TAC group-mean age at onset, 28.8 [11.3]; mean age at trial, 29.6 [11.0]; male, 63.16%; The CTX group-mean age at onset, 34.4 [12.7]; mean age at trial, 35.9 [12.7]; male, 57.14%). The remission rates were 57.9%, 73.7%, and 78.9% in the TAC group and 14.3%, 42.9%, and 50.0% in the CTX group after 2, 4, and 6 months, respectively. The remission rate at 2 months was significantly higher in the TAC group than in the CTX group (P < 0.05). The remission rates during the 1-year therapy and the 1-year follow-up were higher in the TAC group than in the CTX group (Kaplan-Meier curve, log-rank test, P < 0.001). For patients who achieved remission, the mean (SD) time needed for remission was 48.7 (36.0) days in the TAC group and 85.3 (40.6) days in the CTX group (P < 0.05). During the 1-year therapy and 1-year follow-up periods, 6 of the 15 TAC-treated patients and 1 of the 7 CTX-treated patients relapsed (P = 0.35).
  
  
  CONCLUSIONS
  These findings suggest that TAC therapy was effective compared with IV pulse CTX therapy in treating this select group of Chinese adults with SR-MCN. Both agents were well tolerated although TAC seemed to induce remission more rapidly than IV pulse CTX therapy. Australian New Zealand Clinical Trials Registry: study number ACTR 00362050.
authors.affiliation: Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Heng
authors.initials: H
authors.lastname: Li
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Shi
authors.forename: Hong
authors.initials: H
authors.lastname: Shen
authors.forename: Xiayu
authors.initials: X
authors.lastname: Li
authors.forename: Huiping
authors.initials: H
authors.lastname: Wang
authors.forename: Hongmei
authors.initials: H
authors.lastname: Li
authors.forename: Guangbiao
authors.initials: G
authors.lastname: Xu
authors.forename: Jianghua
authors.initials: J
authors.lastname: Chen
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D002681:China; D015331:Cohort Studies; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005938:Glucocorticoids / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007275:Injections, Intravenous; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009402:Nephrosis, Lipoid / Q000188:drug therapy*; D011241:Prednisone / Q000008:administration & dosage / Q000627:therapeutic use; D020551:Pulse Therapy, Drug; D012074:Remission Induction / Q000379:methods; D016559:Tacrolimus / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D055815:Young Adult
chemical_list: D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D003520:Cyclophosphamide; D011241:Prednisone; D016559:Tacrolimus