Editors' ChoiceKIDNEY INJURY

suPAR news for acute kidney injury?

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Science Translational Medicine  04 Mar 2020:
Vol. 12, Issue 533, eabb0794
DOI: 10.1126/scitranslmed.abb0794

Abstract

suPAR might serve as a biomarker for prediction of acute kidney injury with possible therapeutic implications.

Acute kidney injury or AKI is a common condition, affecting up to one in seven hospitalized patients. AKI is associated with worse patient outcomes, increased healthcare costs as well as future progressive loss of kidney function. With a current dearth of targeted therapies, early prediction of disease development could be an effective strategy for the management of AKI. Now, Hayek et al. showed that circulating levels of soluble urokinase plasminogen activator receptor (suPAR), reflecting immune activation and inflammation might be an early predictive biomarker for AKI. suPAR has been associated previously with kidney disease incidence and progression in many settings. The investigators assessed baseline suPAR levels in three cohorts of patients at risk for AKI: undergoing coronary angiography, undergoing cardiac surgery, and those admitted to the intensive care unit. Increased plasma levels of suPAR were associated with a risk of acute kidney injury within the first week after the procedure or after ICU admission. The addition of suPAR levels to a clinical predictive model modestly improved the area under the curve (AUC) for AKI, indicating better risk prediction.

Although several biomarkers have been studied for AKI prediction, suPAR might also have therapeutic value. The investigators show that mice overexpressing suPAR had worse kidney injury than wild type mice when exposed to a kidney insult. Kidney cells that were exposed to suPAR demonstrated increased energy demand and mitochondrial superoxide generation. These observations indicate that suPAR may play a role in the pathogenesis of kidney injury, in addition to its predictive properties. Pretreatment with a monoclonal antibody targeting suPAR attenuated kidney injury in suPAR-overexpressing mice. This raises the intriguing possibility that by reducing suPAR expression or modulating its signaling could reduce AKI incidence and/or its related complications. This will need to be tested in human trials, but if effective and safe, it would represent a major advance in this devastating condition.

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