Jonathan Lu

Date of Award

10-30-2009

Document Type

Open Access Thesis

Degree Name

Medical Doctor (MD)

First Advisor

Lloyd Cantley

Second Advisor

Chirag Parikh

Abstract

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, we performed a systematic review of studies that related the development or prognosis of AKI to genetic variation. We searched MEDLINE, EMBASE, HuGEnet, SCOPUS and Web of Science 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. 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 4 separate studies. Study populations were primarily premature infants or adults who were critically ill or post-cardiac bypass. Among the studies, 5 different definitions of AKI were used. Only 1 polymorphism, APO E e2/e3/e4, had greater than one study showing a significant impact (p<0.05) on AKI incidence while of gene-gene interactions, this was true only with the IL-6 -174G/C and TNF-α -308G/A combination . The mean quality score of 5.8/10 (range 4-9), heterogeneity in the studies and the dearth of studies precluded additional meta-analysis of the results. 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.

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This is an Open Access Thesis.

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