• Journal of critical care · Apr 2018

    Review Meta Analysis

    Genetic variants and acute kidney injury: A review of the literature.

    • Daniel B Larach, Milo C Engoren, Ellen M Schmidt, and Michael Heung.
    • Department of Anesthesiology, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: dlarach@med.umich.edu.
    • J Crit Care. 2018 Apr 1; 44: 203-211.

    PurposeLimited data exists on potential genetic contributors to acute kidney injury. This review examines current knowledge of AKI genomics.Materials And Methods32 studies were selected from PubMed and GWAS Catalog queries for original data studies of human AKI genetics. Hand search of references identified 3 additional manuscripts.Results33 of 35 studies were hypothesis-driven investigations of candidate polymorphisms that either did not consistently replicate statistically significant findings, or obtained significant results only in few small-scale studies. Vote-counting meta-analysis of 9 variants examined in >1 candidate gene study showed ≥50% non-significant studies, with larger studies generally finding non-significant results. The remaining 2 studies were large-scale unbiased investigations: One examining 2,100 genes linked with cardiovascular, metabolic, and inflammatory syndromes identified BCL2, SERPINA4, and SIK3 variants, while a genome-wide association study (GWAS) identified variants in BBS9 and the GRM7|LMCD1-AS1 intergenic region. All studies had relatively small sample sizes (<2300 subjects). Study heterogeneity precluded candidate gene and GWA meta-analysis.ConclusionsMost studies of AKI genetics involve hypothesis-driven (rather than hypothesis-generating) candidate gene investigations that have failed to identify contributory variants consistently. A limited number of unbiased, larger-scale studies have been carried out, but there remains a pressing need for additional GWA studies.Copyright © 2017 Elsevier Inc. All rights reserved.

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