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Use of mammalian target of rapamycin inhibitors in patient with autosomal dominant polycystic kidney disease: an updated meta-analysis

  • Nephrology - Original Paper
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Abstract

Purpose

Mammalian target of rapamycin (mTOR) inhibitors were previously considered a potential therapy for autosomal dominant polycystic kidney disease (ADPKD), but prior studies remained controversial about their efficacy. We performed an updated meta-analysis regarding the therapeutic and adverse effects of mTOR inhibitors in patients with ADPKD.

Methods

We systematically searched Cochrane Library, PubMed, EMBASE, and Medline for randomized controlled trials (RCTs) comparing mTOR inhibitors to placebo in ADPKD patients up to August 2019. We calculated weighted mean differences (WMDs) for total kidney volume (TKV), estimated glomerular filtration rates (eGFRs), and weighted odds ratios (ORs) for treatment-related complications between the treatment and the placebo groups, using the random effects model.

Results

We retrieved a total of 9 RCTs enrolling 784 ADPKD patients receiving rapamycin, sirolimus, or everolimus between 2009 and 2016. The WMDs of TKV and eGFR from baseline to the last measurement were − 31.54 mL (95% confidence interval [CI] − 76.79 to 13.71 mL) and 2.81 mL/min/1.73 m2 (95% CI − 1.85 to 7.46 mL/min/1.73 m2), respectively. Patients receiving mTOR inhibitors had a significantly increased risk of any adverse effects (OR 5.92, 95% CI 3.53–9.94), with the most common ones being aphthous stomatitis (OR 15.45, 95% CI 9.68–24.66) and peripheral edema (OR 3.49, 95% CI 1.31–9.27) compared to placebo users.

Conclusions

mTOR inhibitors did not significantly influence renal progression in patients with ADPKD, but were associated with a higher risk of complications. Whether mTOR inhibitors can be an add-on option or second-line agents remain undetermined.

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Data availability

The datasets generated during and/or analyzed during the current study are not publicly available but are available from the corresponding author on reasonable request.

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Funding

The study was financially sponsored by Taipei Medical University Shuang-Ho Hospital. The sponsors have no role in the study design, data collection, analysis, and result interpretation of this study.

Author information

Author notes

  1. Chun-Hung Lin and Mei-Yi Wu contributed equally to this work.

Authors and Affiliations

  1. Department of Orthopedics, Far Eastern Memorial Hospital, New Taipei City, Taiwan

    Chun-Hung Lin

  2. Department of Internal Medicine, National Taiwan University Hospital BeiHu Branch, National Taiwan University College of Medicine, Taipei, Taiwan

    Chia-Ter Chao

  3. Graduate Institute of Toxicology, National Taiwan University College of Medicine, No. 1, Section 1 Jen-Ai Rd., Taipei, 10051, Taiwan

    Chia-Ter Chao

  4. Department of Nephrology, Taipei Medical University-Shuang Ho Hospital, Taipei, Taiwan

    Mei-Yi Wu & Mai-Szu Wu

  5. Division of Nephrology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

    Mei-Yi Wu & Mai-Szu Wu

  6. Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan

    Mei-Yi Wu & Wei-Cheng Lo

  7. Department of Primary Care Medicine, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan

    Mei-Yi Wu

  8. School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

    Tsu-Chen Lin

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  1. Chun-Hung Lin
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Contributions

Study design: CHL, MYW, WCL; data analysis: CHL, WCL, TCL; article drafting: CHL, MYW, WCL, TCL, CTC; all authors approved the final version of the manuscript.

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Correspondence to Chia-Ter Chao.

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Lin, CH., Chao, CT., Wu, MY. et al. Use of mammalian target of rapamycin inhibitors in patient with autosomal dominant polycystic kidney disease: an updated meta-analysis. Int Urol Nephrol 51, 2015–2025 (2019). https://doi.org/10.1007/s11255-019-02292-1

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  • DOI: https://doi.org/10.1007/s11255-019-02292-1

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