Tacrolimus is an alternative therapy option for the treatment of adult steroid-resistant nephrotic syndrome: a prospective, multicenter clinical trial

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• 作者：Li Fan (1)
  Qinghua Liu (1)
  Yunhua Liao (2)
  Zhibin Li (1) (3)
  Yulian Ji (1)
  Zhenhua Yang (2)
  Jian Chen (4)
  Junzhou Fu (5)
  Jinli Zhang (6)
  Yaozhong Kong (7)
  Ping Fu (8)
  Tanqi Lou (9)
  Zhengrong Liu (10)
  Xueqing Yu (1)
  Wei Chen (1)
  
• 关键词：Tacrolimus ; Nephrotic syndrome ; Steroid ; resistant ; Refractory ; Glomerulonephritis
• 刊名：International Urology and Nephrology
• 出版年：2013
• 出版时间：April 2013
• 年：2013
• 卷：45
• 期：2
• 页码：459-468
• 全文大小：273KB
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• 作者单位：Li Fan (1)
  Qinghua Liu (1)
  Yunhua Liao (2)
  Zhibin Li (1) (3)
  Yulian Ji (1)
  Zhenhua Yang (2)
  Jian Chen (4)
  Junzhou Fu (5)
  Jinli Zhang (6)
  Yaozhong Kong (7)
  Ping Fu (8)
  Tanqi Lou (9)
  Zhengrong Liu (10)
  Xueqing Yu (1)
  Wei Chen (1)
  
  1. 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
  2. Department of Nephrology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
  3. Epidemiology Research Unit, Translational Medicine Research Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
  4. Department of Nephrology, Fuzhou General Hospital, Fuzhou, China
  5. Department of Nephrology, The First Municipal People’s Hospital of Guangzhou, Guangzhou, China
  6. Department of Nephrology, The People’s Hospital of Yunnan Province, Kunming, China
  7. Department of Nephrology, The First Municipal People’s Hospital of Foshan, Foshan, China
  8. Department of Nephrology, The West China Hospital of Sichuan University, Chengdu, China
  9. Department of Nephrology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
  10. Department of Nephrology, The Nanfang Hospital, Southern Medical University, Guangzhou, China
  
• ISSN：1573-2584

文摘

Background 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. Methods 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 5-0?ng/ml for the first 6?months and 4-?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 ?.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 ?.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. Results 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. Conclusions 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.