Biomarkers Consortium – Clinical Evaluation and Qualification of Translational Kidney Safety Biomarkers

The Problem
When conducting clinical trials of any drugs that could cause acute kidney injury, Researchers need biomarkers that can detect such injuries both to ensure the safety of patients and to characterize the drug’s side effects.
The Solution
This project will advance the qualification of biomarkers to monitor kidney safety during early-stage clinical trials in order to detect and prevent drug-induced acute kidney injury.


The Biomarkers Consortium’s Kidney Safety Project aims to facilitate clinical regulatory qualification of translational biomarkers for drug-induced acute kidney injury (AKI). Such biomarkers will be used to monitor kidney safety in early clinical drug development and during treatment courses of individual patients. The project includes both a “learn” and “confirm” phase. The learning phase consisted of retrospective analyses of data from mesothelioma patients and healthy volunteers to help prioritize the novel biomarkers that seem to be the most promising candidates for further validation via a prospective analysis. A panel of eight-translational urinary kidney safety biomarkers was selected for the confirmatory phase, including: albumin, total protein, kidney injury molecule-1 (KIM-1), clusterin, cystatin c, neutrophil gelatinase-associated lipocalin (NGAL), osteopontin (OPN) and N-acetyl-beta-D-glucosaminidase (NAG). These biomarkers harbor tubular enzymes and other proteins that are induced and released into the urine in response to cellular injury and/or stress and inflammation. Furthermore, individual biomarkers in the panel were selected based on their location in the nephron to ensure the panel’s response regardless of the initial site of the nephrotoxic injury.

The confirmatory phase studies include two prospective observational clinical trials that treat patients with either aminoglycosides or cisplatin. These studies seek to confirm the predictive validity of this set of urine biomarkers that reliably change in response to AKI prior to irreversible kidney injury at lower levels of drug exposures or at earlier time points than when traditional measures of kidney damage (serum creatinine and BUN) increase. After formal prospective qualification, these biomarkers are expected to be used in the following activities: 1) each biomarker (individually or in groups) could be used to make real-time decisions so that dose escalation of a drug may be paused or stopped in an individual patient or an entire dose-cohort of subjects when a pre-specified threshold is exceeded; and 2) these thresholds will enable conclusions on an individual subject basis that AKI induced by a drug that is potentially toxic to the kidney, and thereby inform clinical dose selection and possibly subsequent go/no-go drug development decisions in Phase 1 and Phase 2 trials.


Public-Sector Partners

  • National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
  • U.S. Food and Drug Administration (FDA)

Private-Sector Partners

  • Amgen, Inc.*
  • AstraZeneca Pharmaceuticals LP*
  • Critical Path Institute – Predictive Safety Testing Consortium*
  • Eli Lilly and Company
  • Johnson & Johnson*
  • Eli Lilly and Company*
  • Merck Sharp & Dohme Corp.*
  • Pacific Biomarkers
  • Pfizer Inc.*
  • Pharmaceutical Product Development, LLC (PPD)

Academic Partners

  • Brigham and Woman’s Hospital
  • Dana Farber Cancer Institute
  • MD Anderson Cancer Center
  • National Jewish Health
  • University of Minnesota
  • University of Southern California
  • University of Utah

*Provided financial or in-kind support for this program.

FNIH Contact


  • Provide the data needed to advance the clinical qualification and broader acceptance of new translational biomarkers for monitoring kidney safety to support early clinical drug development.
  • Reliably measure changes in these biomarkers in response to a drug-induced AKI at lower exposures, at earlier times and prior to irreversible damage.
  • Improve the clinical diagnosis of drug-induced AKI during drug development.

Results & Accomplishments

In 2018, the FNIH Biomarkers Consortium achieved an impressive milestone by receiving the first ever qualification of a clinical safety biomarker awarded by the FDA. The qualification applies to a composite measure of six urine biomarkers that reliably change in response to drug-induced kidney injury prior to irreversible damage and earlier than traditional biomarkers. This set of biomarkers can now be used to aid in the detection of acute kidney injury in healthy volunteers during early phase clinical trials. This will help improve the development of safe and effective medicines where concern has been raised that an investigational drug may cause kidney injury.


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