霉酚酸酯治疗原发性肾病综合征的临床观察

Mycophenolate mofetil in the treatment of primary nephrotic syndrome

目的 研究霉酚酸酯 (MMF)治疗原发性难治性肾病综合征的疗效及其安全性。方法 41例患者经肾活检证实为难治性肾病综合征。其中轻微病变 (包括微小病变肾病和系膜增生性肾小球肾炎 ) 19例 ;膜性肾病 (MN) 18例 ;局灶节段性肾小球硬化症 (FSGS) 3例和膜增殖性肾小球肾炎(MPGN) 1例。采用皮质激素和MMF联合治疗 :MMF初始剂量 1.0～ 2 .0g/d ,3个月后可适当减量 ,疗程至少 6个月 ;口服强的松 2 0～ 6 0mg/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。部分病例在治疗 6个月结束时进行了重复肾活检。结果 MMF联合皮质激素可以使轻微病变和膜性肾病患者尿蛋白定量下降和血清白蛋白上升 (P <0 .0 0 1)。 11/ 19例轻微病变第 4周起效。 12 / 19例获得完全缓解 ,激素依赖者可顺利减量。 6 / 18例MN第 4周起效 ,13/ 18例有效 ,但仅 3例获得临床完全缓解。MPGN和 2 / 3例FSGS患者无效。治疗过程中 4例因感染一过性尿蛋白增加 ,去除诱因后好转 ,不需停止用药。 1例因血红蛋白下降退出观察。其他副作用均可耐受而未影响用药完成观察。治疗前后肾功能无变化。 4例患者重复肾活检证实肾脏病理无明显改变。结论 MMF是治疗难治性原发性肾病综合征有效的免疫抑制剂 。

Objective To investigate the efficacy and safety of mycophenolate mofetil (MMF) on treating refractory primary nephrotic syndrome. Methods Forty one patients with refractory nephrotic syndrome confirmed by renal biopsy, 19 with minor lesion (minimal lesion nephropathy and mesangial proliferative glomerulonephritis), 18 with membranous nephropathy (MN), 3 with focal segmental glomerulosclerosis (FSGS), and one with mesangioproliferative glomerulonephritis (MPGN), were treated by MMF combined with prednisone. The initial dosage of MMF was 1.0～2.0 g/d for three months and then the dosage was tapered gradually. The duration of MMF treatment was at least six months. Prednisone at the dose of 20～60 g/d was used at the beginning of the combined treatment and then the dosage was tapered gradually. Follow up interview was conducted regularly. Four patients were rebiopsyed by the end of observation. Results The combined treatment of MMF/prednisone decreased the urine protein and elevated the serum albumin significantly among patients with minor lesion and MN ( P <0.001). All patients with minor lesion achieved clinical remission. Eleven of the nineteen cases responded within four weeks, and twelve of them obtained complete clinical remission. The dosage of prednisone could be tapered smoothly among the steroid dependent patients. Thirteen of the eighteen patients with MN achieved remission, however only six responded within four weeks and only three of them achieved complete clinical remission. During the treatment, four patients experienced transient increase of urine protein due to infection and recovered spontaneously without alteration of treatment. Side effects were tolerable except one case was withdrawn due to the decrease of hemoglobin. Renal function remained stable during the treatment. No obvious alteration could be found in renal biopsy by the end of treatment among four patients. Conclusion MMF is an effective and safe immunosuppressive agent for refractory nephrotic syndrome.