Westhoff T H, Schmidt S, Zidek W, Beige J, van der Giet M
Medical Clinic IV, Nephrology, Charité, Campus Benjamin Franklin, Berlin, Germany.
Clin Nephrol. 2006 Jun;65(6):393-400. doi: 10.5414/cnp65393.
Steroid resistance and steroid dependence constitute a major problem in the treatment of minimal-change disease and focal segmental glomerulosclerosis (FSGS). Cyclophosphamide and cyclosporine are well-established alternative immunomodulating agents, whereas data on FK 506 (tacrolimus) are rare.
The present work provides data from 10 patients of an open, monocentric, non-randomized, prospective trial. Five patients with steroid-dependent minimal-change nephrotic syndrome, 1 patient with steroid-refractory minimal-change disease and 4 patients with steroid-refractory FSGS were started on tacrolimus at trough levels of 5 10 microg/l. In case of steroid-dependence, prednisolone was tapered off in presence oftacrolimus within one month.
Within 6 months, complete remission was achieved in 5 patients (50%) and partial remission in 4 patients (40%), yielding a final response rate of 90%. One patient was primarily resistent to tacrolimus (steroid-refractory minimal-change), another patient became secondarily resistant to tacrolimus after an initial remission (steroid-refractory FSGS). Average proteinuria significantly decreased by 77% from 9.5 +/- 1.4 - 2.2 +/- 1.1 g/day (p < 0.01). Serum protein significantly raised from 55.0 +/- 1.9 - 64.6 +/- 1.9 g/l (p < 0.01). Tacrolimus induced non-significant increases of blood glucose (4.9 +/- 0.1 - 5.1 +/- 0.2 mmol/l), systolic blood pressure (131.4 +/- 7.1 - 139.0 +/- 7.6 mmHg) and creatinine (93.2 +/- 13.9 103.2 +/- 15.3 mmol/l). Five patients have been tapered off tacrolimus so far, nephrotic syndrome relapsed in 4 of them (80%). Relapse occurred at tacrolimus levels between 2.6 and 6.9 ng/ml.
Our data suggest that tacrolimus may be a promising alternative to cyclosporine both in steroid-resistant and steroid-dependent nephrotic syndrome.
类固醇抵抗和类固醇依赖是微小病变病和局灶节段性肾小球硬化症（FSGS）治疗中的主要问题。环磷酰胺和环孢素是公认的替代免疫调节剂，而关于FK 506（他克莫司）的数据很少。
本研究提供了一项开放、单中心、非随机、前瞻性试验中10例患者的数据。5例类固醇依赖型微小病变肾病综合征患者、1例类固醇抵抗型微小病变病患者和4例类固醇抵抗型FSGS患者开始使用他克莫司，谷浓度为5～10μg/L。对于类固醇依赖型患者，在使用他克莫司的情况下，泼尼松龙在1个月内逐渐减量。
6个月内，5例患者（50%）完全缓解，4例患者（40%）部分缓解，最终缓解率为90%。1例患者对他克莫司原发性耐药（类固醇抵抗型微小病变），另1例患者在初始缓解后对他克莫司继发性耐药（类固醇抵抗型FSGS）。平均蛋白尿从9.5±1.4g/天显著下降77%至2.2±1.1g/天（p<0.01）。血清蛋白从55.0±1.9g/L显著升高至64.6±1.9g/L（p<0.01）。他克莫司使血糖（4.9±0.1mmol/L至5.1±0.2mmol/L）、收缩压（131.4±7.1mmHg至139.0±7.6mmHg）和肌酐（93.2±13.9mmol/L至103.2±15.3mmol/L）有非显著性升高。目前5例患者已停用他克莫司，其中4例（80%）肾病综合征复发。复发发生在他克莫司浓度为2.6至6.9ng/ml之间。
我们的数据表明，他克莫司在类固醇抵抗型和类固醇依赖型肾病综合征中可能是环孢素的一种有前景的替代药物。
