Low-dose tacrolimus in treating lupus nephritis refractory to cyclophosphamide: a prospective cohort study

Clin Exp Rheumatol. Jan-Feb 2013;31(1):62-8. Epub 2012 Aug 30.


Objectives: This study aims to assess the efficacy and safety of low-dose tacrolimus therapy in patients with refractory lupus nephritis (LN) who were resistant to cyclophosphamide (CYC).

Methods: A total of 26 LN patients (4 men and 22 women) with persistent proteinuria who were resistant to CYC treatment (>8 g in less than 6 months) were enrolled. Tacrolimus was initiated at 2 mg/day (if patient weight <60 kg) or 3mg/day (if patient weight ≥60 kg), administered in two divided doses. Prospective data on daily proteinuria, serum albumin level, and serologic lupus activity were collected for 6 months.

Results: Mean age at baseline was 29.36±9.45 years. Mean urinary protein significantly decreased from 6.91±4.50 g at baseline to 1.11±1.10 g at 6 months (p<0.001). Mean serum album level significantly increased from 25.56±7.94 g/L at baseline to 38.12±2.42 g/L at 6 months (p<0.001). Mean systemic lupus erythematosus disease activity index (SLEDAI) score decreased from 11.42±6.74 at baseline to 3.61±2.73 at 6 months (p<0.001). Complete or partial response was observed in 88.46% of patients receiving tacrolimus therapy at 6 months. Twenty-one patients achieved partial or complete remission in two months. There was no significant difference among tacrolimus levels for patients with complete, partial, or no response. The effective dosage in this study was 2-3 mg/day for patients with complete or partial response to tacrolimus. Tacrolimus was well tolerated at the administered dose, though one patient developed severe lung infection.

Conclusions: Our results suggested tacrolimus at low dosage and serum level to be potentially effective and safe for treatment in patients with LN resistant to sufficient CYC therapy. A tacrolimus dosage of 2-3 mg daily appears to be effective and safe.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Analysis of Variance
  • Biomarkers / blood
  • Cyclophosphamide / administration & dosage*
  • Drug Resistance*
  • Female
  • Humans
  • Immunosuppressive Agents / administration & dosage*
  • Immunosuppressive Agents / adverse effects
  • Linear Models
  • Lupus Nephritis / blood
  • Lupus Nephritis / complications
  • Lupus Nephritis / diagnosis
  • Lupus Nephritis / drug therapy*
  • Male
  • Prospective Studies
  • Proteinuria / drug therapy
  • Proteinuria / etiology
  • Remission Induction
  • Serum Albumin / metabolism
  • Serum Albumin, Human
  • Severity of Illness Index
  • Tacrolimus / administration & dosage*
  • Tacrolimus / adverse effects
  • Time Factors
  • Treatment Failure
  • Young Adult


  • ALB protein, human
  • Biomarkers
  • Immunosuppressive Agents
  • Serum Albumin
  • Cyclophosphamide
  • Tacrolimus
  • Serum Albumin, Human