小剂量环孢素A联合小剂量激素治疗原发性肾病综合征疗效观察

Preliminary observation of low-dose cyclosporine A combined with low-dose prednisone in treatment of patients with primary nephrotic syndrome

目的观察小剂量环孢素A(CsA)联合小剂量强的松在原发性肾病综合征治疗中的疗效、不良反应及其与足量强的松的比较。方法 67例原发性肾病综合征均经肾活检病理检查证实,前瞻性非随机观察18个月以上。治疗组(n=41):小剂量CsA联合小剂量强的松,其中难治性肾病综合征8例,强的松0.5mg·kg-1·d-1+CsA2.5mg·kg-1·d-1,强的松最大剂量30mg/d,连服2～3个月后每隔2～4周强的松、CsA在原剂量基础上交替递减10%或持续应用原剂量。对照组(n=26):足量强的松组,强的松1.0mg·kg-1·d-1,强的松最大剂量60mg/d,连服2～3个月后每隔2～4周在原剂量基础上递减10%。其中10例联合环磷酰胺(CTX)治疗,CTX0.8g·次-1·月-1,加入生理盐水500ml静脉滴注,或口服0.1g/d,CTX总量6.0～8.0g。观察两组治疗前、治疗3、6、9、12、18个月24h尿蛋白定量(MTP)、肝功能(TP、ALB、ALT)、肾功能(Cr、UA)、血糖、血脂(TC、LDL)及不良反应。结果两组患者治疗后MTP及ALB水平较治疗前均明显好转(P<0.01),治疗18个月后治疗组和对照组总有效率(显效+有效)分别为80.5%和84.6%,两组间无统计学差异(P>0.05)。治疗组12个月时完全缓解率有升高趋势(P<0.01),但18个月后又降至正常,28例显效患者18个月后停CsA随访3年中有5例(17.9%)复发,复发后再次治疗仍然有效。治疗组不良反应:齿龈增生1例,血压升高4例,血尿酸升高6例,停药后或用药均可控制。结论与足量强的松治疗原发性肾病综合征比较,小剂量CsA联合小剂量强的松具有等同疗效,又可减少CsA及激素毒副作用,为治疗原发性肾病综合征提供了一个比较经济有效安全的方法。

Objective To evaluate the efficacy and safety of combining low-dose cyclosporine A（CsA） and prednisone in induction therapy for patients with primary nephrotic syndrome （PNS）,and their comparison with furl amount of prednisone.Methods 67 cases of PNS were confirmed by renal biopsy examination and prospective nonrandomized analyzed for more than 18 months.Treatment group：low-dose CsA combined low-dose prednisone,41 cases,including 8 cases of refractory nephrotic syndrome.Patients were treated with CsA 2.5 mg · kg-1 · d-1 combined with prednisone 0.5 mg · kg-1 · d-1 （maximum dose of prednisone 30 mg/d）.After 2 to 3 months,dose of prednisone and CsA turn down 10％ every 2 to 4 weeks or continuous application of the original dose.Control group：enough prednisone,26 patients,patients were treated with prednisone 1.0 mg · kg-1 · d-1 （maximum dose of prednisone 60 mg/d）.After 2 to 3 months,dose of prednisone turn down 10％ every 2 to 4 weeks.10 cases combined with cyclophosphamide（CTX） treatment（CTX 0.8 g/month in 500 ml normal saline intravenous or oral 0.1 g/d,CTX total 6.0-8.0 g）.Clinical parameters （MTP,ALB,ALT,CR,UA,GLU,TC and LDL） and adverse effects were estimated before and after therapy.Results MTP and ALB levels were significantly improved in both groups （P ＜0.01） after treatment.The total effective rates were 80.5％ and 84.6％ after 18 months（P ＞0.05）.The creatinine in treatment group tended to increase after 12 months of treatment （P ＜ 0.01）,but returned to normal after 18 months.5 cases （17.9％） recurrened in 28 cured cases after stopping CsA up for 3 years.Some adverse effects （gingival hyperplasia,hypertension,increase of serum uric acid increased） occurred during CsA therapy,but could be easily controlled.Conclusions Low-dose CsA combined low-dose prednisone is adequate efficient for treatment of primary nephrotic syndrome compared to that with the enough prednisone.At the same time reducing the side effects of CsA and corticosteroids which provides a more safe and cost-effective way for the treatment of primary nephrotic syndrome.