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

  • Nephrology - Original Paper
  • Published:
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Abstract

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 5–10 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.

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.

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Acknowledgments

We thank Prof. Richard Johnson (University of Colorado, Denver, CO, USA) for his critical comments and inputs to this study and manuscript. The data were presented in part in poster form at the APCN 2010, JUN 5–8, Seoul, Korea. This work was supported by grants from National Natural Science Foundation of China (Nos. 30971378, 30871166). Dr. Wei Chen was supported by her grant from Outstanding Young Teachers Foundation of Sun Yat-sen University (09ykpy23), ISN Fellowship, and Scientific and Technologic Committee of Guangdong province (Nos. 2009B030801129, 2005B30701002). Dr Xueqing Yu was supported by Sun Yat-sen University Clinical Research 5010 Program, International Joint Research Program of Ministry of Science and Technology of China (No. 2009DFA32820), and the 973 project (2011CB50400050).

Conflict of interest

Astellas Pharmaceuticals supplied the tacrolimus used in this study, but it played no role in the design and conduct of this study as well as in the analysis and the interpretation of results. Writing and publication of the manuscript were not contingent on the approval of Astellas Pharmaceuticals.

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Authors and Affiliations

  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

    Li Fan, Qinghua Liu, Zhibin Li, Yulian Ji, Xueqing Yu & Wei Chen

  2. Department of Nephrology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China

    Yunhua Liao & Zhenhua Yang

  3. Epidemiology Research Unit, Translational Medicine Research Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China

    Zhibin Li

  4. Department of Nephrology, Fuzhou General Hospital, Fuzhou, China

    Jian Chen

  5. Department of Nephrology, The First Municipal People’s Hospital of Guangzhou, Guangzhou, China

    Junzhou Fu

  6. Department of Nephrology, The People’s Hospital of Yunnan Province, Kunming, China

    Jinli Zhang

  7. Department of Nephrology, The First Municipal People’s Hospital of Foshan, Foshan, China

    Yaozhong Kong

  8. Department of Nephrology, The West China Hospital of Sichuan University, Chengdu, China

    Ping Fu

  9. Department of Nephrology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China

    Tanqi Lou

  10. Department of Nephrology, The Nanfang Hospital, Southern Medical University, Guangzhou, China

    Zhengrong Liu

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  1. Li Fan
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  2. Qinghua Liu
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  15. Wei Chen
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Correspondence to Wei Chen.

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Fan, L., Liu, Q., Liao, Y. et al. Tacrolimus is an alternative therapy option for the treatment of adult steroid-resistant nephrotic syndrome: a prospective, multicenter clinical trial. Int Urol Nephrol 45, 459–468 (2013). https://doi.org/10.1007/s11255-012-0205-1

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