UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Rationale and Design of the Genetic Contribution to Drug Induced Renal Injury (DIRECT) Study

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. Green open access

[thumbnail of Davenport_Rationale and Design of the Genetic Contribution to Drug Induced Renal Injury (DIRECT) Study_VoR.pdf]
Preview
Text
Davenport_Rationale and Design of the Genetic Contribution to Drug Induced Renal Injury (DIRECT) Study_VoR.pdf - Published Version

Download (710kB) | Preview

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
Downloads since deposit
51Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item