title: Outcomes of tacrolimus therapy in adults with refractory membranous nephrotic syndrome:  a prospective, multicenter clinical trial.
abstract: BACKGROUND
  The treatment of adult refractory idiopathic membranous nephropathy with steroid and other immunosuppressant-resistant nephrotic syndrome can be a significant challenge. The authors investigated the efficacy and safety of tacrolimus (TAC) as a promising regimen.
  
  
  METHODS
  A prospective, multicenter trial was conducted in 9 nephrology centers from 2006 to 2008. Fourteen patients were enrolled. In conjunction with prednisone, TAC was started at 0.05 mg/kg/d, titrated to achieve a trough blood level of 5 to 10 ng/mL for the first 6 months, then reduced to 4 to 6 ng/mL for the subsequent 6 months. The primary endpoints included complete or partial remission. Secondary endpoints included relapse, change of clinical parameters and adverse events.
  
  
  RESULTS
  After 12 months, complete remission was achieved in 35.7% of patients and partial remission in 42.9%, yielding a response rate of 78.6%. Proteinuria, serum albumin, cholesterol, triglyceride and low-density lipoprotein were improved significantly (P < 0.001, P < 0.001, P = 0.002, P = 0.01, P = 0.004, respectively). Proteinuria and serum albumin were significantly improved (42.0% ± 13.2%, P = 0.02; 15.2% ± 4.5%, P = 0.01, respectively) even after the first month of treatment. One patient relapsed during the subsequent 6 months of follow-up. Adverse events included 2 cases of infection and 1 case each of hyperglycemia, hand tremor, sudden death (nondrug related) and diarrhea.
  
  
  CONCLUSIONS
  TAC plus prednisone may be an alternative therapeutic option for steroid and general immunosuppressant-resistant membranous nephrotic syndrome patients, with a favorable safety profile. However, given the limitation of a small number of patients in this trial, further study with a larger number and longer follow-up is needed.
authors.affiliation: Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Key Laboratory of Nephrology, Ministry of Health, Guangzhou, China. vvchen66@gmail.com
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Liu
authors.forename: Yunhua
authors.initials: Y
authors.lastname: Liao
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Yang
authors.forename: Jian
authors.initials: J
authors.lastname: Chen
authors.forename: Junzhou
authors.initials: J
authors.lastname: Fu
authors.forename: Jinli
authors.initials: J
authors.lastname: Zhang
authors.forename: Yaozhong
authors.initials: Y
authors.lastname: Kong
authors.forename: Ping
authors.initials: P
authors.lastname: Fu
authors.forename: Tanqi
authors.initials: T
authors.lastname: Lou
authors.forename: Zhengrong
authors.initials: Z
authors.lastname: Liu
authors.forename: Yulian
authors.initials: Y
authors.lastname: Ji
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Li
authors.forename: Xueqing
authors.initials: X
authors.lastname: Yu
mesh_terms: D000328:Adult; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D009404:Nephrotic Syndrome / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D011241:Prednisone / Q000008:administration & dosage; D011446:Prospective Studies; D016559:Tacrolimus / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D011241:Prednisone; D016559:Tacrolimus