title: Long-term tacrolimus-based immunosuppressive treatment for young patients with lupus nephritis: a prospective study in daily clinical practice.
abstract: BACKGROUND
  The optimal long-term treatment for lupus nephritis (LN) in pubertal patients remains to be determined. Tacrolimus (Tac) inhibits T cell activation, and is therefore expected to be effective in patients with LN. However, little has been published about the long-term efficacy and safety of Tac-based immunosuppressive treatment of young patients with LN in daily clinical practice.
  
  
  METHODS
  Nineteen consecutive patients with biopsy-proven LN were recruited for an open-label, prospective, long-term Tac-based treatment regimen. Tac was administered once daily at a dose of 3 mg as induction- or reinduction-maintenance treatment. Four patients (21%) with new-onset LN received mizoribine at a dose of 150 mg once daily in addition to Tac. Treatment outcomes were defined by the European Consensus Lupus Activity Measurement (ECLAM) index, urinary protein/creatinine ratio (Up/cr), serum creatinine and serological lupus markers (complement C3, complement hemolytic activity, CH50, and anti-dsDNA antibody titer). Data on these parameters were collected prospectively. The median follow-up was 42 months.
  
  
  RESULTS
  Baseline characteristics of the patients were as follows: mean age, 18 years; Up/cr, 0.89 ± 1.17; serum C3, 68.1 ± 23.2 mg/dl (normal, 79-152 mg/dl); serum CH50, 26.4 ± 10.5 U/ml (normal, 23-46 U/ml); serum anti-dsDNA antibody titer, 69.3 ± 67.5 IU/ml (normal, <12.0 IU/ml); serum creatinine, 0.55 ± 0.18 mg/dl, and ECLAM index, 4.6 ± 1.9. Despite gradually tapering the dose of concomitantly administered prednisolone, a marked improvement compared with baseline values was observed in all outcome measures as early as 3 months after the initiation of treatment, and the favorable changes persisted throughout the treatment period in most of the patients. Sustained improvements in the outcome measures compared with the baseline values were confirmed after a mean of 42 months of treatment: ECLAM index, 1.1 ± 1.1; serum CH50, 36.0 ± 12.8 U/ml, anti-dsDNA antibody titer, 22.5 ± 26.5 IU/ml (all p < 0.01); Up/cr ratio, 0.35 ± 0.58, and serum C3 level, 79.7 ± 17.6 mg/dl (both p < 0.05). Serum creatinine level remained within the normal range in all the study participants. Complete response was achieved in 12 patients (63%), and a partial response was achieved in 5 patients (26%). The remaining 2 patients showed no response. No serious adverse effects were observed.
  
  
  CONCLUSIONS
  The data suggest that long-term, relatively low-dose Tac-based immunosuppressive treatment is beneficial and has low cytotoxicity, and therefore represents an attractive option for the treatment of young patients with LN in daily clinical practice. Further studies involving a larger number of patients are needed to confirm these results.
authors: Department of Pediatrics, Hirosaki University Hospital, Hirosaki, Japan. hirotana@cc.hirosaki-u.ac.jp
authors: Hiroshi
authors: H
authors: Tanaka
authors: Shojiro
authors: S
authors: Watanabe
authors: Tomomi
authors: T
authors: Aizawa-Yashiro
authors: Eishin
authors: E
authors: Oki
authors: Naonori
authors: N
authors: Kumagai
authors: Kazushi
authors: K
authors: Tsuruga
authors: Etsuro
authors: E
authors: Ito
mesh_terms: D000293:Adolescent; D002648:Child; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007564:Japan; D008137:Longitudinal Studies; D008181:Lupus Nephritis / Q000175:diagnosis* / Q000188:drug therapy*; D008297:Male; D016559:Tacrolimus / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D016559:Tacrolimus