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

Chun Hung Lin, Chia Ter Chao*, Mei Yi Wu, Wei Cheng Lo, Tsu Chen Lin, Mai Szu Wu

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

11 Scopus citations

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.

Original languageEnglish
Pages (from-to)2015-2025
Number of pages11
JournalInternational Urology and Nephrology
Volume51
Issue number11
DOIs
StatePublished - 01 11 2019
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2019, Springer Nature B.V.

Keywords

  • Autosomal dominant polycystic kidney disease
  • End-stage renal disease
  • Estimated glomerular filtration rate
  • Mammalian target of rapamycin
  • Total kidney volume

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