Department of Nephrology, The First Affiliated Hospital, Key Laboratory of Nephrology, Ministry of Health of China, Sun Yat-sen University, 58# Zhongshan Road II, Guangzhou 510080, China.
Int Urol Nephrol. 2013 Apr;45(2):459-68. doi: 10.1007/s11255-012-0205-1. Epub 2012 Jun 9.
The optimal therapy for adult steroid-resistant nephrotic syndrome (SRNS) remains a therapeutic challenge. We investigated the efficacy and safety of tacrolimus as a promising regimen in Chinese adult patients.
A prospective, multicenter trial was conducted in 9 nephrology centers from 2006 to 2008, in patients with SRNS (defined as failure to respond to 1 mg/kg/day of prednisone for 8, and 16 weeks, in focal segmental glomerulosclerosis). Patients were treated with tacrolimus (TAC) plus prednisone for 12 months. TAC dose was titrated to achieve a target trough blood concentration of 5-10 ng/ml for the first 6 months and 4-6 ng/ml for the subsequent 6 months. The primary outcomes included complete or partial remission [complete remission (CR): proteinuria <0.3 g/24 h, with serum albumin ≥ 3.5 g/dl and stable renal function; partial remission (PR): proteinuria between 0.3 and 3.5 g/24 h and a decrease of at least 50 % from the baseline level, with serum albumin ≥ 3.0 g/dl and stable renal function]. Secondary end-points included relapse rate, changes of clinical parameters (proteinuria, serum albumin, and lipid profile) and adverse events.
Twenty-four patients with SRNS were enrolled. After 6 months of therapy, CR was achieved in 58.3 % of patients and PR in 16.7 %, yielding a final response rate of 75.0 %. The decrease in proteinuria was 43.1 ± 17.5 % after the first month of treatment (P < 0.001). Complete or PR was achieved in 6 of 8 patients with minimal change disease, 4 of 6 patients with mesangioproliferative glomerulonephritis (MsPGN), 6 of 7 patients with focal segmental glomerulosclerosis (FSGS), and all 2 patients with IgA nephropathy. Two patients (1 with MsPGN and 1 with FSGS) experienced relapses during the subsequent 6 months of follow-up. Adverse events included infection, hand tremor, diarrhea, acute reversible or persistent nephrotoxicity.
In conjunction with prednisone, TAC may be an alternative therapeutic regimen for adult SRNS patients. However, adverse events in these patients should be carefully monitored, especially at the beginning of treatment. Randomized controlled trials with longer follow-up are warranted.
成人激素抵抗型肾病综合征（SRNS）的最佳治疗方法仍然是一个治疗挑战。我们研究了他克莫司作为一种有前途的方案在中国成年患者中的疗效和安全性。
2006 年至 2008 年，9 个肾病中心进行了一项前瞻性、多中心试验，纳入了 SRNS 患者（定义为对 1mg/kg/天的泼尼松治疗 8 周和 16 周无反应，局灶节段性肾小球硬化）。患者接受他克莫司（TAC）加泼尼松治疗 12 个月。TAC 剂量滴定，使目标谷浓度在最初 6 个月达到 5-10ng/ml，随后 6 个月达到 4-6ng/ml。主要结局包括完全或部分缓解[完全缓解（CR）：蛋白尿<0.3g/24h，血清白蛋白≥3.5g/dl 且肾功能稳定；部分缓解（PR）：蛋白尿 0.3-3.5g/24h，较基线水平下降至少 50%，血清白蛋白≥3.0g/dl 且肾功能稳定]。次要终点包括复发率、临床参数（蛋白尿、血清白蛋白和血脂谱）变化和不良事件。
24 例 SRNS 患者入组。治疗 6 个月后，58.3%的患者达到 CR，16.7%的患者达到 PR，总缓解率为 75.0%。治疗第 1 个月蛋白尿下降 43.1±17.5%（P<0.001）。微小病变性肾病患者中 6 例达到 CR，6 例达到 PR；系膜增生性肾小球肾炎患者中 4 例达到 CR，6 例达到 PR；局灶节段性肾小球硬化患者中 7 例达到 CR，2 例达到 PR；IgA 肾病患者中 2 例达到 CR。2 例患者（1 例系膜增生性肾小球肾炎，1 例局灶节段性肾小球硬化）在随后的 6 个月随访中复发。不良事件包括感染、手震颤、腹泻、急性可逆或持续肾毒性。
与泼尼松联合应用时，他克莫司可能是成人 SRNS 患者的另一种治疗方案。然而，应密切监测这些患者的不良事件，尤其是在治疗开始时。需要进行随访时间更长的随机对照试验。
