FDA-approval required before clinical use

A new blood test has the potential to reveal whether a person recently diagnosed with type 1 diabetes is already at risk for kidney failure—information that might allow physicians to alter the course of treatment and slow disease progression.

This is the hope of Harvard Stem Cell Institute (HSCI) scientists at Brigham and Women’s Hospital who recently demonstrated that a laboratory test could detect, in the blood of mice and humans, the presence of a protein released as a result of kidney damage. The work, which has already been replicated, was published in the Journal of the American Society of Nephrology.

A urine test for kidney damage already exists using this protein, called KIM-1 (short for kidney injury molecule-1), but is only approved to determine whether drugs in clinical trials have toxic side effects. The test, while the best among kidney damage analyses, is imperfect, as accurate results depend on the concentration of a person’s urine. If approved for clinical use, a KIM-1 blood test would be more sensitive and accurate than anything that currently exists.

“We looked at patients over an average of 10 years and we found that for those with worsening kidney disease, there was an increase in the levels of KIM-1 in the blood,” said Joseph Bonventre, MD, PhD, the study’s senior author, who is an HSCI Executive Committee member and Chief of the Renal Unit and Director of the Bioengineering Division at Brigham and Women’s Hospital.

The researchers were also able to look back at the 10 years of data and use KIM-1 levels to predict which populations of type 1 diabetes patients, even if they had very good kidney function initially, would eventually develop kidney failure. Typically, one third of people with type 1 diabetes experience significant kidney disease.

“This is an exciting molecule in terms of its utility as a biomarker, but this is the first study, and it will take time for this test to be approved for routine use,” Bonventre said. “As a clinician, knowing that a patient is potentially at higher risk would make me highly motivated to do all I could in order to decrease their chance of having end stage kidney disease.”

Bonventre’s research team will next be looking to use the KIM-1 blood test to see whether it performs well to detect kidney problems for other types of patients, such as those with kidney tumors or proteinuria, a very early form of type 1 diabetes. There is also evidence to suggest that KIM-1 is actually detrimental to the kidney over the long term, so looking at therapeutic agents to target the molecule may also reduce the progression of disease.

This research was a multi-collaborative effort between Brigham and Women’s Hospital, the University of Liverpool, the Joslin Diabetes Center, Harvard Medical School, the University of Edinburgh, and the Harvard School of Public Health. Venkata Sabbisetti, PhD, an Instructor in Medicine at Brigham and Women’s Hospital, was first author on the study.

The work was supported by the National Institutes of Health, Brigham and Women’s Hospital, the Juvenile Diabetes Research Foundation, the CKD Biomarker Consortium, the Centre for Drug Safety Science, the Royal Society, and the Wellcome Trust.

Cited: Sabbisetti, et. al., Blood kidney injury molecule-1 is a biomarker of acute and chronic kidney injury and predicts progression to ESRD in type 1 diabetes, Journal of the American Society of Nephrology (June 5, 2014), doi: 10.1681/ASN.2013070758