For the past eight years, Dennis Moledina, MD, PhD, assistant professor of medicine (nephrology), has been searching for a new method to determine if a patient with acute kidney injury (AKI) has acute interstitial nephritis (AIN), a common cause of AKI. AIN is a reaction to commonly used medications that causes kidney inflammation and injury.
“Right now, we don’t have any blood or urine tests available to diagnose AIN, so patients suspected of having AIN often have to undergo a kidney biopsy, which has risks, including bleeding and infection,” Moledina explained. A biopsy can also cause a delay in treatment, which is associated with lower chances of kidney function recovery, he said.
My hope is that the new test, in addition to being convenient, will minimize the need for biopsies and enable physicians to diagnose AIN without unnecessarily stopping the medications or therapy their patients are on.
Dennis Moledina, MD, PhD
Moledina first became interested in finding a way to diagnose AIN as a trainee at Yale School of Medicine (YSM). One of his patients at the time was a veteran with AKI, who was taking proton pump inhibitors for acid reflux. Proton pump inhibitors can induce AIN. Because the patient had had stents implanted, he was also taking Plavix and aspirin, medicines that can increase bleeding complications following a kidney biopsy.
“His kidney function kept worsening, and we couldn’t obtain a kidney biopsy,” Moledina said. “At the time, I really wished I had a test to determine if he had AIN.”
Differentiating between AIN and other causes of acute kidney injury can be challenging for physicians because most patients with AIN have no specific sign or symptom, Moledina said. The ability to diagnose AIN is important because the disease, unlike other causes of kidney injury, can be treated, improving the care of patients with acute kidney injury, he said.
In a study led by Moledina, a team of researchers from YSM, Johns Hopkins School of Medicine, and Harvard Medical School performed urine proteomic analysis to identify biomarkers, or indicators, that can distinguish AIN from other causes of AKI. The study found that, in a cohort of 88 participants, 31 of whom had biopsy-confirmed AIN, urinary levels of the protein CXCL9 was higher in those with AIN. The authors also noted higher levels of CXCL9 in kidney tissue of patients with AIN than in controls. The findings, which were validated in two external cohorts, were published in the new paper “Identification and validation of urine CXCL9 as a biomarker for diagnosis of acute interstitial nephritis.”
With this discovery, Moledina plans to develop a new dipstick test to be used at the patient’s bedside. “My hope is that the new test, in addition to being convenient, will minimize the need for biopsies and enable physicians to diagnose AIN without unnecessarily stopping the medications or therapy their patients are on,” Moledina said.
To learn more, read the paper in the Journal of Clinical Investigation.
In addition to Moledina, authors of the paper include Wassim Obeid, Rex N. Smith, Ivy Rosales, Meghan E. Sise, Gilbert Moeckel, Michael Kashgarian, Michael Kuperman, Kirk N. Campbell, Sean Lefferts, Kristin Meliambro, Markus Bitzer, Mark A. Perazella, Randy L. Luciano, Jordan S. Pober, Lloyd G. Cantley, Robert B. Colvin, F. Perry Wilson, and Chirag R. Parikh.
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