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

Abstract Purpose Limited data exists on potential genetic contributors to acute kidney injury. This review examines current knowledge of AKI genomics. Materials and methods 32 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. Results 33 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 ( Conclusions Most 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.