Abstract: Objective To investigate the efficacy and adverse effects of sequential mycophenolate mafetil (MMF) after 3 months and 6 months of cyclophosphamide (CTX) in children with type Ⅲ or Ⅳ lupus nephritis (LN).Methods This is a non-randomized controlled trial. The objects were children with type Ⅲ or Ⅳ LN. Parents of these children were fully aware of the benefits and adverse effects of sequential MMF after 3 months (group A) and 6 months (group B) of CTX induction therapy. According to the parents' decision, these children were divided into group A and B. The efficacy and adverse events of the two groups were followed up for 1 year. The main outcome indicators of efficacy are as follows. Complete remission: blood routine, renal function, albumin, erythrocyte sedimentation rate are normal and C3≥0.73 g·L^-1, C4≥0.1 g·L^-1, anti-ds-DNA antibody is negative with two methods of immunofluorescence and ELISA. At the same time, 24 h urine protein should be lower than150 mg. Partial remission: Any one of the following is achieved:①24 h urine protein is 50% lower than that before treatment, and the total amount is <3.5 g·24 h^-1.②Serum creatinine and urine protein/creatinine are improved by 50%.③Serum creatinine is improved by 50% and urinary protein/creatinine is <1.0. And laboratory tests are improved compared to before the treatment.Results Thirty three children were retrospectively analyzed. All the children were admitted to the Peking Union Medical College Hospital from January 2012 to January 2018. The age of onset, age of kidney biopsy, gender, season of onset, living environment, type of renal pathology, incidence of family history were similar in two groups. The efficacy and side effects have no significant difference between the two groups, at the end of treatment (3 months in group A, 6 months in group B) and 12 months after treatment. There was no significant difference in efficacy at 3 months between two groups. There was no significant difference in efficacy at 6 months and 1 year between two groups. At 3 months, the cumulative dose of CTX (mg·kg^-1) were (94.0±20.5) and (104.1±34.8) respectively in group A and B. There was no significant difference (P=0.39). There was no correlation between the mean CTX cumulative amount and the efficacy at 3 months and 6 months(r= 0.95, P= 0.051). There was no significant difference in the incidence of adverse events between the two groups. The adverse events were mainly white blood cell reduction, infection, gastrointestinal discomfort and irregular menstruation. Hair loss and hemorrhagic cystitis did not happen because of CTX.Conclusions equencing of MMF after 3 months or 6 months of CTX treatment has no effect on efficacy and adverse effects for children with proliferative lupus nephritis.

Key words: Cyclophosphamide, Mycophenolate mofetil, Proliferative lupus nephritis in children, Remission induction therapy