Abstract: Objective: To investigate the efficacy and safety of leflunomide (LEF) in the treatment of refractory primary nephrotic syndrome. Methods: Fifty-one patients with refractory nephrotic syndrome, 26 with minor lesions (8 with minimal lesion nephropathy and 16 with mesangial proliferative glomerulonephritis), 16 with membranous nephropathy (MN), 6 with focal segmental glomerulosclerosis (FSGS), and 3 with mesangioproliferative glomerulonephritis (MPGN), were treated by LEF combined with prednisone. The initial dosage of LEF was 50mg/d, 3 days later， 30mg/d, for three months and then the dosage was gradually tapered off. The duration of LEF treatment was 6 to 12 months. Prednisone at a dosage of 20-60mg/d was used at the beginning of the was gradually tapered off. Follow up interviews were regularly conducted. Results: The urine protein was decreased by the combined treatment of LEF/prednisone and the serum albumin significantly elevated among patients with minor lesion and MN (P＜0.001). All patients with minor lesions achieved clinical remission. Fifteen of the twenty-six cases responded within four weeks and seventeen of them obtained complete clinical remission. The dosage of prednisone could be smoothly tapered off among the steroid dependent patients. Eleven of the sixteen patients with MN achieved remission, however, only five responded within four weeks and only three of them achieved complete clinical remission. During the treatment, six patients experienced a transient increase of the urine protein due to infection and spontaneously recovered without an alteration of treatment. Side effects were tolerable. Renal function remained stable during the treatment. Conclusion: LEF is an effective and safe immunosuppressive agent for refractory nephrotic syndrome.

Key words: Refractory nephrotic syndrome, Leflunomide