ObjectiveThe purpose of this study was to assess the efficacy,safety and optimal dose of tacrolimus monotherapy in patients with refractory lupus nephritis(LN) who were resistant to cyclophosphamide(CYC).MethodsA total of 14 LN patients (2 men and 12 women) with persistent proteinuria who were resistant to CYC treatment more than 8 g for half a year were enrolled.Tacrolimus was initiated at 2 mg/d (patient weight＜60 kg) or 3 mg/d(patient weight≥60 kg) which was administered in two divided doses.Prospective data on daily proteinuria,serum album level and serologic lupus activity were collected and followed for 6 months.ANOVA and Pearson correlation analysis were used for statistical analysis.Results Mean age at baseline was(30±9) years.Mean urinary protein decreased significantly from(6.2±5.1) g at baseline to (1.1±0.9) g at 6 months (F=16.21,P＜0.01).Mean serum album level increased significantly from (27.9±9.7) g/L at baseline to(37.8±2.2) g/L at 6 months(F=16.71,P＜0.01 ).Complete or partial response was observed in 86％ of patients receiving tacrolimus therapy.The effective dosage in this study was 0.03-0.06mg·kg-1·d-1 of the patients who had complete response or partial response to tacrolimus.The tacrolimus level in partially and completely responding patients was less than 3 ng/ml.There was no significant difference among blood tacrolimus levels of complete,partial,and no response patients [(1.6-±0.4),(2.0±0.6) and (22±1.1) ng/nl],respectively).No definite correlation was found between efficacy and tacrolimus level.Tacrolimus was well tolerated at current dose,besides one with new onset hypertension and one with alopecia.ConclusionOur results suggest that tacrolimus at low dosage and serum level is potentially effective and safe for the treatment　of patients with LN and persistent proteinuria resistant to CYC.The optimal dosage of tacrolimus for LN may　be 0.03-0.06 mg·kg-1·d-1.