title: Short-term outcomes of induction therapy with tacrolimus versus cyclophosphamide for active lupus nephritis: A multicenter randomized clinical trial.
abstract: BACKGROUND
  Intravenous cyclophosphamide with prednisone is an effective treatment for lupus nephritis, but with significant toxicities. We compared the efficacy and safety of tacrolimus versus intravenous cyclophosphamide as induction therapy.
  
  
  METHODS
  Multicenter noninferiority randomized controlled trial.
  
  
  METHODS
  81 patients with biopsy-proven lupus nephritis from 9 nephrology centers in China from 2006-2008.
  
  
  METHODS
  Prednisone and either tacrolimus (n = 42) or intravenous cyclophosphamide (n = 39) for 6 months. Tacrolimus was started at 0.05 mg/kg/d and titrated to achieve a trough blood concentration of 5-10 ng/mL. Intravenous cyclophosphamide was initiated at 750 mg/m² of body surface area, then adjusted to 500-1,000 mg/m² every 4 weeks for a total of 6 pulse treatments.
  
  
  METHODS
  The primary outcome was complete remission (proteinuria with protein excretion <0.3 g/24 h, serum albumin ≥3.5 g/dL, normal urinary sediment, and normal or stable serum creatinine level) at 6 months. Response (complete or partial remission), clinical parameters, and adverse effects were secondary end points.
  
  
  RESULTS
  After the 6-month induction therapy, the tacrolimus group achieved higher cumulative probabilities of complete remission and response (52.4% vs 38.5% and 90.5% vs 82.1%, respectively) than the intravenous cyclophosphamide group, but differences were not statistically significant (log-rank test, P = 0.2 and P = 0.7, respectively). Proteinuria [corrected] was significantly decreased in tacrolimus- versus intravenous cyclophosphamide-treated patients after the first month of treatment, even with adjustment for baseline proteinuria (protein excretion, 1.76 vs 2.40 g/d; P = 0.02 for the log-transformed analysis). [corrected] After treatment, serum creatinine levels and estimated glomerular filtration rates were not significantly different between treatment groups. Adverse effects, such as leukopenia and gastrointestinal symptoms, were less frequent in the tacrolimus group.
  
  
  CONCLUSIONS
  Nonblinded, small sample size, and short duration of follow-up.
  
  
  CONCLUSIONS
  In conjunction with prednisone, induction therapy with tacrolimus is at least as efficacious as intravenous cyclophosphamide and prednisone in producing complete remission of lupus nephritis and has a more favorable safety profile.
authors.affiliation: Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Xueqing
authors.initials: X
authors.lastname: Tang
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Liu
authors.forename: Weiying
authors.initials: W
authors.lastname: Chen
authors.forename: Ping
authors.initials: P
authors.lastname: Fu
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.forename: Yunhua
authors.initials: Y
authors.lastname: Liao
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Yang
authors.forename: Jinli
authors.initials: J
authors.lastname: Zhang
authors.forename: Jian
authors.initials: J
authors.lastname: Chen
authors.forename: Tanqi
authors.initials: T
authors.lastname: Lou
authors.forename: Junzhou
authors.initials: J
authors.lastname: Fu
authors.forename: Yaozhong
authors.initials: Y
authors.lastname: Kong
authors.forename: Zhengrong
authors.initials: Z
authors.lastname: Liu
authors.forename: An
authors.initials: A
authors.lastname: Fan
authors.forename: Shaoqi
authors.initials: S
authors.lastname: Rao
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Li
authors.forename: Xueqing
authors.initials: X
authors.lastname: Yu
mesh_terms: D000328:Adult; D000893:Anti-Inflammatory Agents / Q000009:adverse effects / Q000627:therapeutic use; D002681:China; D003404:Creatinine / Q000097:blood; D003520:Cyclophosphamide / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D008181:Lupus Nephritis / Q000097:blood / Q000188:drug therapy* / Q000652:urine; D008297:Male; D011241:Prednisone / Q000009:adverse effects / Q000627:therapeutic use; D011507:Proteinuria / Q000652:urine; D012074:Remission Induction; D012189:Retrospective Studies; D016559:Tacrolimus / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D007166:Immunosuppressive Agents; D003520:Cyclophosphamide; D003404:Creatinine; D011241:Prednisone; D016559:Tacrolimus