title: Efficacy and safety of tacrolimus for induction therapy in patients with active lupus nephritis.
abstract: After the completion of a double-blind placebo-controlled trial, tacrolimus (TAC) was approved for the treatment of lupus nephritis (LN) in Japan. However, the approved maximal dose, 3 mg/day, is almost half the dose used for induction therapy outside Japan. In this study, we retrospectively evaluated the efficacy and safety of low-dose TAC (≤3 mg/day) for induction therapy in 13 adult patients (2 men and 11 women) with active LN. Eight patients were treated for LN flares. Twelve patients underwent renal biopsies: 8 with class IV, 2 with class III + V, 1 with class IV + V, and 1 with class V renal histology, according to the International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification. The mean initial doses of prednisone and TAC were 34.6 ± 14.5 and 2.7 ± 0.6 mg/day, respectively. All the patients achieved a complete remission (CR) at 7.7 ± 6.7 months (mean ± SD) after the last administration of TAC, except for 2 patients who discontinued TAC treatment; 1 because of worsening systemic lupus erythematosus and 1 because of hypertension. Two patients experienced a flare-up after achieving CR. The mean blood TAC concentration 12 h after the last administration (C12) was significantly lower among the patients with flare-ups than among those with a sustained CR (1.5 ± 1.5 vs. 5.1 ± 1.9 ng/mL, P = 0.034). These data showed that low-dose TAC was effective for induction therapy in patients with active LN, although a lower TAC concentration may be associated with a poor outcome.
authors.affiliation: Department of Medicine and Clinical Science, Gunma University Graduate School of Medicine, 3-39-22 Showa, Maebashi, Gunma 371-8511, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Takahashi
authors.forename: Keiju
authors.initials: K
authors.lastname: Hiromura
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Sakurai
authors.forename: Takayuki
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Ikeuchi
authors.forename: Akito
authors.initials: A
authors.lastname: Maeshima
authors.forename: Yoriaki
authors.initials: Y
authors.lastname: Kaneko
authors.forename: Takashi
authors.initials: T
authors.lastname: Kuroiwa
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Nojima
mesh_terms: D000305:Adrenal Cortex Hormones / Q000008:administration & dosage; D000328:Adult; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006977:Hypertension, Renal / Q000139:chemically induced / Q000188:drug therapy; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D008181:Lupus Nephritis / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011507:Proteinuria / Q000188:drug therapy; D012074:Remission Induction; D012189:Retrospective Studies; D016559:Tacrolimus / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood
chemical_list: D000305:Adrenal Cortex Hormones; D047228:Angiotensin II Type 1 Receptor Blockers; D007166:Immunosuppressive Agents; D016559:Tacrolimus