Clinical trial NCT02159209: The Drug Induced Renal Injury Consortium
Official title: The Genetic Contribution to Drug Induced Renal Injury: The Drug Induced Renal Injury Consortium (DIRECT)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Acute Kidney Injury
Adverse Drug Reaction
Acute Kidney Failure
Kidney Failure
Kidney Disease
Keywords: Acute Kidney Injury
Adverse Drug Reaction
Acute Kidney Failure
Kidney
Kidneys
Lead sponsor: University of California, San Diego
Sponsor class: OTHER
Collaborators: name: International Serious Adverse Event Consortium
First posted: 2014-06-09
Enrollment: 634
Sex: ALL
Minimum age (years): 2
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: This is a prospective observational cohort study of patients who have developed DIRI. Patients will be identified through two main approaches;

1. Recall and review of medical records of patients who were suspected to have DIRI
2. Concurrent identification of patient under active treatment.

Patients who developed DIRI in their previous care provided will be identified through a review of kidney biopsy logs or nephrology consults previously made.

Brief summary: Some medications are known to cause kidney damage because the person is allergic to the medication while others cause direct damage to the kidney because they are toxic at certain concentrations. Risk factors for developing kidney damage have been identified for some medications but not for all. Patients who are exposed to these important medications and develop problems with their kidneys may have some genetic risk. The purpose of this study is to determine the genetic risk factors for drug induced kidney injury. A better understanding of the role of genetics for the development of kidney injury from medications will allow us to better select medications, improve effectiveness of treatment and minimize harm.


Eligibility criteria: Inclusion Criteria:

* Patients age 2 years and older
* Exposure to a candidate drug for at least 24 hours (see above)
* Patients who have developed DIRI as defined by the primary criteria
* Written informed consent or assent and consent obtained
* If patient lacks capacity to consent then surrogate consent will be obtained

Exclusion Criteria:

* Patients with a history of or have a kidney transplant
* Patients with a history of or have a bone marrow transplant
* Patients with Chronic Kidney Disease stage 5 (eGFR \< 15 mL/min/1.73m2)
* Patients on 3 or more causal drugs
* Patients with no history or time course on drug exposure
* Patient who, in the opinion of the Investigator, is not suitable to participate in the study.
* Unable to obtain written informed consent or assent
* Unable to obtain surrogate consent for patients who lack capacity

Primary outcomes:
measure: Identify genes that predispose to dose dependent (Type A) or hypersensitivity (Type B) during drug induced nephrotoxicity.
timeFrame: At time of enrollment
Secondary outcomes:
measure: To identify specific alterations in drug metabolism pathways that contribute to drug induced renal injury with different drugs.
timeFrame: DNA sample collected at time of enrollment.
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama, Birmingham
state: Alabama
city: San Diego
country: United States
facility: University of California, San Diego
state: California
city: San Diego
country: United States
facility: Rady Children's Hospital
state: California
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Albany
country: United States
facility: St. Peter's Hospital
state: New York
city: New York
country: United States
facility: Jacobi Medical Center
state: New York
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital
state: Ohio
city: Cochabamba
country: Bolivia
facility: Universidad del Valle, Cochabamba
city: Montreal
country: Canada
facility: Hopital Sacre Coeur & Universite de Montreal
state: Quebec
city: Santiago
country: Chile
facility: Universidad de Los Andes
city: Banjara Hills
country: India
facility: CARE Hospitals
state: Hyderabad
city: Chandigarh
country: India
facility: Postgraduate Institute of Research, Chandigarh
city: Newcastle upon Tyne
country: United Kingdom
facility: Newcastle University
state: Tyne and Wear
city: Leeds
country: United Kingdom
facility: St James's University Hospital
state: West Yorkshire
city: London
country: United Kingdom
facility: Royal Free Hospital
city: London
country: United Kingdom
facility: Guy's & St Thomas's Hospital
city: Nottingham
country: United Kingdom
facility: University of Nottingham
Study officials:
affiliation: University of California, San Diego
name: Ravindra Mehta, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mehta RL, Awdishu L, Davenport A, Murray PT, Macedo E, Cerda J, Chakaravarthi R, Holden AL, Goldstein SL. Phenotype standardization for drug-induced kidney disease. Kidney Int. 2015 Aug;88(2):226-34. doi: 10.1038/ki.2015.115. Epub 2015 Apr 8.