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

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art_AWDISHU_Rationale_and_Design_of_the_Genetic_Contribution_to_2016.PDF (693.63 KB)
Citações na Scopus
8
Tipo de produção
article
Data de publicação
2016
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
ELSEVIER SCIENCE INC
Autores
AWDISHU, Linda
NIEVERGELT, Caroline M.
DAVENPORT, Andrew
MURRAY, Patrick T.
CERDA, Jorge
CHAKARAVARTHI, Raj
RAO, Satish P. Ramachandra
HOLDEN, Arthur
GOLDSTEIN, Stuart L.
Citação
KIDNEY INTERNATIONAL REPORTS, v.1, n.4, p.288-298, 2016
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Introduction: Nephrotoxicity from drugs accounts for 18% to 27% of cases of acute kidney injury. Determining a genetic predisposition maypotentially 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 controlsmatched on biogeographic ancestry to determine whether there is agenetic 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.
Palavras-chave
AKI, antimicrobials, calcineurin inhibitors, nephrotoxicity, NSAIDs, pharmacogenomics
URI
https://observatorio.fm.usp.br/handle/OPI/31855
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Coleções
Artigos e Materiais de Revistas Científicas - FM/Outros
Artigos e Materiais de Revistas Científicas - ODS/03