Congratulations Dr. Sylvie Breton!

TITLE: Diagnostic for Acute Kidney Injury Associated with Cardiovascular Diseases


DESCRIPTION:  Acute kidney injury (AKI) is a frequent complication in hospitalized patients, including those undergoing cardiac surgery. However, two critical barriers to the clinical management of these critically ill patients remain the need for better methods for early prognosis/diagnosis of AKI and therapeutic options to prevent/mitigate AKI. Uncontrolled inflammation is a leading cause of AKI. Injured cells in organs remote from the kidney (e.g. heart, brain, lungs, limbs) release UDP-glucose (UDP-G), a danger-associated molecular pattern (DAMP) molecule, which then builds up in the kidney, triggering inflammation. Consistent with this, we have data suggesting that high level of UDP-G in the urine of patients is predictive of the onset of AKI.  We previously showed that UDP-G binds to the purinergic receptor P2Y14 in the kidney.  This binding increases the expression of chemokines that attract neutrophils and monocytes into the kidney. In studies supported by a B-BIC Pilot award, we demonstrated that prophylactic blocking of the UDP-G/P2Y14 signaling pathway with a potent, selective P2Y14 antagonist, PPTN, reduced renal inflammation and histological damage and improved renal function after renal ischemic reperfusion injury in mice. To complement this therapeutic approach, the aim of this DRIVE Award proposal is to develop a clinical-grade UDP-G assay for the prognosis/diagnosis of AKI. This can serve as a stand-alone diagnostic for AKI or as a theranostic for P2Y14-targeted therapeutics.