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

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.

• Authors: Chun-Hung Lin, Chia-Ter Chao, Mei-Yi Wu, Wei-Cheng Lo, Tsu-Chen Lin, Mai-Szu Wu
• Journal: International urology and nephrology (Int Urol Nephrol) Vol. 51 Issue 11 Pg. 2015-2025 (Nov 2019) ISSN: 1573-2584 [Electronic] Netherlands
• PMID: 31578673 (Publication Type: Journal Article, Meta-Analysis)

Chemical References

• TOR Serine-Threonine Kinases

Topics

• Humans
• Polycystic Kidney, Autosomal Dominant (drug therapy)
• TOR Serine-Threonine Kinases (adverse effects, antagonists & inhibitors)
• Treatment Outcome