Principal Investigator Joseph Bonventre
Project Website http://bonventrelab.bwh.harvard.edu/?q=biomarker-core-facility
The kidney is a major target organ for the toxic effects induced by a wide range of chemical and physical agents and drug-induced nephrotoxicity plays a major role in the high incidence and prevalence of acute kidney injury in both hospitalized and non hospitalized patients. The tests available to detect kidney toxicity in the preclinical and clinical studies are either invasive and difficult to quantitate or non-invasive and non specific and insensitive. Easily quantifiable and sensitive biomarkers can be influential in every phase of therapeutics, from drug discovery and preclinical evaluation through each phase of clinical trials and into post- marketing studies.
In the quest to identify an early diagnostic biomarker for kidney injury we cloned Kidney Injury Molecule-1 (KIM-1), which is a transmembrane glycoprotein that is upregulated more than any other of the 30,000 genes tested after acute kidney injury in rats.
We have found that the ectodomain of KIM-1 is shed from cells in vitro and in vivo into the urine in rodents and humans after proximal tubular kidney injury. In the preclinical and clinical studies urinary KIM-1 serves as an early diagnostic indicator of kidney injury as compared to any of the conventional biomarkers, e.g. plasma creatinine, BUN, glycosuria, increased proteinuria or increased urinary NAG, g-GT, AP levels. We first developed an ELISA to measure KIM-1 in rodent and human urine samples and recently we have developed a microbead-based assay to quantitate urinary KIM-1 that is more sensitive, has a greater dynamic range and requires less urine volume (30 ml) and reagents than the conventional ELISA. Through several collaborations around the world we have validated this assay in more than 4000 urine samples from rodents and humans using 15 mechanistically different models of kidney injury/toxicity.
We are currently validating Kidney Injury Molecule-1 as an early diagnostic and prognostic biomarker in human urine samples from large multicentric cross sectional and prospective studies and comparing its efficacy to 4-6 other potential biomarkers.
We welcome collaborations from across the globe to further the biomarker research and for a comprehensive list of ongoing preclinical and clinical collaborations, click here. We also have specific recommendations on optimal conditions for urine collection, storage and shipment on the sample preparation and shipping instruction page.