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

The Biomarkers Consortium’s Kidney Safety Project aims to advance clinical regulatory qualification and broader acceptance of new translational biomarkers of drug-induced acute kidney injury (AKI) that will be used for monitoring kidney safety in early clinical drug development and during course of individual patient therapies. The project is designed to include a learn-and-confirm phase. The learn phase consists of retrospective analyses of mesothelioma patients and healthy volunteer data to establish a prioritization for the novel biomarkers that seem most promising to be further validated through a prospective analysis. Biomarkers being evaluated include urinary: 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).

The predictive validity of these promising biomarkers will be confirmed through the prospective analyses of data collected from two observational clinical trials that treat patients with either aminoglycosides or cisplatin treatment—aiming to validate important biomarkers of AKI that perform better than serum creatinine and BUN (the currently used biomarkers of AKI). Following formal prospective qualification, these biomarkers are expected to be used in decisions: 1) to formulate appropriate stopping criteria to halt dosing for a given patient or within an entire cohort, or 2) to cease dose escalation in Phase 1 or Phase 2 trials, and 3) to inform clinical dose selection, or possibly subsequent go – no go drug development decision making.


  • To 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.
  • To reliably measure the change in response of these biomarkers to a drug-induced acute kidney injury at lower exposures, at earlier times and in more exposed test subjects prior to irreversible damage
  • To improve the clinical diagnosis of acute drug-induced kidney injury during drug development.


User's Guide: Kidney Safety Composite Measure Biomarker for Use in Clinical Development: The FNIH Biomarkers Consortium Kidney Safety Biomarker Project Team and the Critical Path Institute’s Predictive Safety Testing Consortium’s Nephrotoxicity Working Group have authored a comprehensive document that describes and outlines the use of the qualified composite measure biomarker for use in Phase 1 clinical trials (with healthy volunteers as subjects) in conjunction with standard measures of kidney function.

Critical Path Institute Press Release (March 14, 2019): A press release announcing the public availability of the User's Guide was shared coincident with World Kidney Day.

FNIH Press Release (October 25, 2018): FNIH Biomarkers Consortium and Critical Path Institute Achieve the First Ever Qualification of a Clinical Safety Biomarker by the U.S. Food and Drug Administration

FDA Letter of Support: Submitted by Critical Path Institute's (C-Path) Predictive Safety Testing Consortium (PSTC), Nephrotoxicity Working Group (NWG) in support of further use of urinary biomarkers Osteopontin and Neutrophil Gelatinase-associated Lipocalin (NGAL) for kidney safety monitoring in early clinical drug development


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

Steve Hoffmann, Director, Inflammation and Immunity,