Searching for genes that matter in acute kidney injury: a systematic review.
OBJECTIVE
Identifying patients who may develop acute kidney injury (AKI) remains challenging, as clinical determinants explain only a portion of individual risk. Another factor that likely affects risk is intrinsic genetic variability. Therefore, a systematic review of studies was performed that related the development or prognosis of AKI to genetic variation.


METHODS
MEDLINE, EMBASE, HuGEnet, SCOPUS, and Web of Science were searched for articles from 1950 to Dec 2007. Two independent researchers screened articles using predetermined criteria. Studies were assessed for methodological quality via an aggregate scoring system.


RESULTS
The 16 included studies were of cohort or case-cohort design and investigated 35 polymorphisms in 21 genes in association with AKI. Fifteen gene-gene interactions were also investigated in four separate studies. Study populations were primarily premature infants or adults who were critically ill or postcardiac bypass patients. Among the studies, five different definitions of AKI were used. Only one polymorphism, APO E e2/e3/e4, had greater than one study showing a significant impact (P < 0.05) on AKI incidence. The mean quality score of 5.8/10 (range four to nine), heterogeneity in the studies, and the dearth of studies precluded additional meta-analysis of the results.


CONCLUSIONS
Current association studies are unable to provide definitive evidence linking genetic variation to AKI. Future success will require a narrow consensus definition of AKI, rigorous epidemiologic techniques, and a shift from a priori hypothesis-driven to genome-wide association studies.
Lu
Jonathan C T
JC
Yale University School of Medicine, New Haven, Connecticut, USA.
Coca
Steven G
SG
Patel
Uptal D
UD
Cantley
Lloyd
L
Parikh
Chirag R
CR
D055371:Acute Lung Injury / Q000453:epidemiology* / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D023281:Genomics; D006801:Humans; D015994:Incidence; D011110:Polymorphism, Genetic