The Drug Induced Renal Injury Consortium

Overview

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.

Full Title of Study: “The Genetic Contribution to Drug Induced Renal Injury: The Drug Induced Renal Injury Consortium (DIRECT)”

Study Type

  • Study Type: Observational
  • Study Design
    • Time Perspective: Prospective
  • Study Primary Completion Date: December 2015

Arms, Groups and Cohorts

  • Drug Induced Renal Injury (DIRI)
    • This is a prospective observational cohort study of patients who have developed acute kidney injury Stage 2 or a glomerular disorder following exposure to specific drugs that have been associated with DIRI.

Clinical Trial Outcome Measures

Primary Measures

  • Identify genes that predispose to dose dependent (Type A) or hypersensitivity (Type B) during drug induced nephrotoxicity.
    • Time Frame: At time of enrollment
    • Blood Draw (20 cc) and urine collection (80cc)

Secondary Measures

  • To identify specific alterations in drug metabolism pathways that contribute to drug induced renal injury with different drugs.
    • Time Frame: DNA sample collected at time of enrollment.
    • We will perform a GWAS to examine the association of common genetic variants with the development of DIRI. For assessing association between a common SNP and the risk of DIRI, association tests will be undertaken to compare genotype frequencies between cases and controls. We will use logistic regression models under the assumption of an additive genetic model and incorporate potential confounders and covariates. Dominant, recessive models will also be checked through alternative coding of the genotype for SNPs approaching significance.

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 2 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Ravindra Mehta
  • Collaborator
    • International Serious Adverse Event Consortium
  • Provider of Information About this Clinical Study
    • Sponsor-Investigator: Ravindra Mehta, Professor of Clinical Medicine – University of California, San Diego
  • Overall Official(s)
    • Ravindra Mehta, MD, Principal Investigator, University of California, San Diego

References

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.

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