来氟米特治疗原发性难治性肾病综合征的多中心临床观察

目的：研究来氟米特（LEF）治疗原发性难治性肾病综合征的疗效及其安全性。方法：难治性肾病综合征患者51例，均行肾活检，其中轻微病变26例（微小病变8例、系膜增生性肾小球肾炎18例）；膜性肾病（MN）16例；局灶节段性肾小球硬化症（FSGS）6例；膜增殖性肾小球肾炎（MPGN）3例。采用皮质激素和LEF联合治疗：LEF初始剂量50mg/d，3d后30mg/d，3月后适当减量，疗程6～12个月，同时口服强的松20～60mg/d,在病情许可的条件下适当加快皮质激素的撤药速度。定期随访并记录副作用。结果：LEF联合皮质激素可以使轻微病变和MN患者尿蛋白定量下降和血清白蛋白上升（P＜0.001）。15/26例轻微病变第4周起效；17/26例获得完全缓解，激素依赖者可顺利减量。5/16例MN第4周起效，11/16有效，3例获得临床完全缓解；1例MPGN和2例FSGS患者有效。治疗过程中6例因感染致尿蛋白增加，诱因清除后好转，未停用药；其他副作用均可耐受而未影响用药及观察。治疗前后肾功能无变化。结论：LEF是治疗难治性原发性肾病综合征有效的免疫抑制剂，其副作用是可以耐受的。

Leflunomide in the treatment of refractory primary nephrotic syndrome

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.