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Authors Xia T, Zhu S, Wen Y, Gao S, Li M, Tao X, Zhang F, Chen W
Received 16 August 2017
Accepted for publication 27 December 2017
Published 28 February 2018 Volume 2018:12 Pages 417—428
DOI https://doi.org/10.2147/DDDT.S149340
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Amy Norman
Peer reviewer comments 3
Editor who approved publication: Dr Sukesh Voruganti
Background: Nephrotoxicity
of calcineurin inhibitors (CNIs) is the major concern for long-term allograft
survival despite its predominant role in current immunosuppressive regime after
renal transplantation. CNI nephrotoxicity is multifactorial with demographic, environmental,
and pharmacogenetic flexibility, whereas studies indicating risk factors for
CNI nephrotoxicity obtained incomplete or conflicting results.
Methods: A systematic review and meta-analysis of risk factors for CNI
nephrotoxicity was performed on all retrieved studies through a comprehensive
research of network database. Data were analyzed by Review Manager 5.2 with
heterogeneity assessed using the Cochrane Q and I 2 tests. CNI nephrotoxicity was primarily indicated with protocol
biopsy or index-based clinical diagnosis, and the secondary outcome was defined
as delayed graft function.
Results: Twelve observational studies containing a total of 2,849 cases
were identified. Donor age (odds ratio [OR], 1.01; 95% CI, 1.01–1.03; p =0.02), recipient zero-time
arteriosclerosis (OR, 1.44; 95% CI, 1.04–1.99; p =0.03),
and CYP3A5*3/*3 genotype (OR,
2.80; 95% CI, 2.63–2.98; p =0.00) were
confirmed as risk factors for CNI nephrotoxicity. Subgroup and sensitivity
analysis claimed donor age as a significant contributor in Asian and Caucasian
areas.
Conclusion: Older donor age, recipient zero-time arteriosclerosis, and CYP3A5*3/*3 genotype might
add up the risk for CNI nephrotoxicity, which could be interpreted into a
robust biomarker system.
Keywords: calcineurin inhibitor, transplantation, nephrotoxicity, risk factor,
systematic review, meta-analysis