Elsevier

Transplantation Proceedings

Volume 46, Issue 1, January–February 2014, Pages 66-74
Transplantation Proceedings

New vistas in transplantation
Renal transplantation
Sirolimus for Treatment of Autosomal-Dominant Polycystic Kidney Disease: A Meta-Analysis of Randomized Controlled Trials

https://doi.org/10.1016/j.transproceed.2013.10.040Get rights and content

Abstract

Background

Autosomal-dominant polycystic kidney disease (ADPKD) is the most common form of cystic kidney disease. The mammalian target of rapamycin (mTOR) pathway is associated with progressive kidney enlargement. The drug sirolimus suppresses mTOR signaling but plays an uncertain role in the treatment of ADPKD. The objective of our study was to conduct a meta-analysis of randomized controlled trials (RCTs) to present an objective appraisal of the efficacy and safety of sirolimus therapy in patients with ADPKD.

Methods

We conducted a meta-analysis of RCTs performed in adults with ADPKD, and compared the effect of sirolimus on total kidney volume (TKV), glomerular filtration rate (GFR), cyst volume, and daily urinary protein excretion. Safety was evaluated based on analysis of blood pressure, lipid profile, complete blood count, infection, and other reported adverse events.

Results

Four RCTs were included. The sirolimus therapy group had smaller TKV than the control group. The mean difference (MD) of TKV post-treatment compared with the control group was −234.74 (P = .01). However, GFR did not reach a statistically significant difference between groups. Standard mean difference (SMD) of GFR after therapy was 0.24 (95% confidence interval [CI], 0.05–0.52; P = .11), but sirolimus seemed to increase urine protein excretion (P = .002). There was no statically significant difference in leukocytes, hemoglobin, platelets, and blood pressure between groups. Aphthous stomatits and pharyngitis are reported more commonly in the sirolimus therapy group compared with the control group (P < .000001).

Conclusions

In ADPKD patients, treatment with sirolimus is safe and can effectively slow kidney growth, but it seems not to slow down the decrease of GFR.

Section snippets

Literature Search and Screen

A comprehensive literature search was undertaken using PUBMED, EMBASE, and Cochrane Library up to March 2013. Search terms including medical subject heading words and text words were related to exposure (Table 1). No publication year or publication language restrictions were applied. References of the identified relevant studies were scrutinized. RCTs of ADPKD patients with GFR >30 mL/min/1.73 m2 treated with sirolimus compared with conventional or placebo treatment were included. We excluded

Literature Search and Characteristics of Studies

A total of 4 RCTs [7], [8], [9], [10] fulfilled eligibility criteria extracted from 92 potentially relevant articles. The detailed steps were in the flow diagram for meta-analysis presented in Figure 1. Characteristics of included RCTs are presented in Table 2. There are 183 early-stage ADPKD patients included in these 4 RCTs. Length of follow-up ranged from 6 to 24 months.

Study Quality

Risk of bias was accessed through a domain-based evaluation tool recommended by the Cochrane Collaboration, which includes

Discussion

With the increasing understanding of the links between the molecular mechanisms of ADPKD and the mTOR signaling pathway, mTOR inhibiters, especially sirolimus, have become a focus of attention in novel therapies for ADPKD. Of 24 interventional trials for ADPKD currently registered with clinicaltrials.gov, 8 studies are about mTOR inhibiters [11]. The aim of this meta-analysis was to determine whether sirolimus could slow the progression of ADPKD and preserve the patients' renal function.

ADPKD

References (18)

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Cited by (0)

Y.-M.L. and Y.S. contributed equally to this work as co-first authors.

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