Awdishu, L;
Nievergelt, CM;
Davenport, A;
Murray, PT;
Macedo, E;
Cerda, J;
Chakaravarthi, R;
... Mehta, RL; + view all
(2016)
Rationale and Design of the Genetic Contribution to Drug Induced Renal Injury (DIRECT) Study.
Kidney International Reports
, 1
(4)
pp. 288-298.
10.1016/j.ekir.2016.08.010.
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Abstract
INTRODUCTION: Nephrotoxicity from drugs accounts for 18% to 27% of cases of acute kidney injury. Determining a genetic predisposition may potentially be important in minimizing risk. The aims of this study are as follows: to determine whether a genetic predisposition exists for the development of drug-induced kidney disease (DIKD), using genome-wide association and whole-genome sequencing studies; to describe the frequency, course, risk factors, resolution and outcomes of DIKD cases; to investigate the role of ethnic/racial variability in the genetics of DIKD; and to explore the use of different tools establishing causality of DIKD. METHODS: A total of 800 patients will be enrolled worldwide and blood samples for DNA collected. Data on the patient risk factors, vital signs, laboratory parameters, drug exposure, and DIKD course will be recorded. A panel of nephrologists will adjudicate all cases. Genome-wide association studies will be conducted using population controls matched on biogeographic ancestry to determine whether there is a genetic predisposition to DIKD. The primary endpoint is the identification of specific drug-related polymorphisms associated with DIKD. Secondary endpoints include the following: frequency of DIKD by causal drug and drug combinations; DIKD genetic variability; exploration of causality assessment tools; risk factor identification; description of the course of DIKD, including mortality and dialysis dependency at hospital discharge and 28 and 90 days post-event. RESULTS: Data are currently being analyzed. Results are pending. DISCUSSION: The Genetic Contribution to Drug Induced Renal Injury (DIRECT) study will be the first observational cohort study to investigate the genetic determinants of DIKD. If the trial is positive, its findings will potentially translate into safer patient outcomes, by genotypic individualization of therapy and minimization of harm.
| Type: | Article |
|---|---|
| Title: | Rationale and Design of the Genetic Contribution to Drug Induced Renal Injury (DIRECT) Study |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.ekir.2016.08.010 |
| Publisher version: | https://doi.org/10.1016/j.ekir.2016.08.010 |
| Language: | English |
| Additional information: | © 2016 International Society of Nephrology. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
| Keywords: | AKI, antimicrobials, calcineurin inhibitors, nephrotoxicity, NSAIDs, pharmacogenomics |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10060369 |
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