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Soluble Urokinase Receptor and Acute Kidney Injury
Study Questions:
Does a high level of soluble urokinase plasminogen activator receptor (suPAR) predispose patients to acute kidney injury (AKI)?
Methods:
The investigators measured plasma levels of suPAR preprocedurally in patients who underwent coronary angiography and patients who underwent cardiac surgery and at the time of admission to the intensive care unit (ICU) in critically ill patients. The authors assessed the risk of AKI at 7 days as the primary outcome and AKI or death at 90 days as a secondary outcome, according to quartile of suPAR level. In experimental studies, they used a monoclonal antibody to urokinase plasminogen activator receptor (uPAR) as a therapeutic strategy to attenuate AKI in transgenic mice receiving contrast material. Cellular bioenergetics and generation of reactive oxygen species in human kidney proximal tubular (HK-2) cells that were exposed to recombinant suPAR were also assessed.
Results:
The suPAR level was assessed in 3,827 patients who were undergoing coronary angiography, 250 who were undergoing cardiac surgery, and 692 who were critically ill. AKI developed in 318 patients (8%) who had undergone coronary angiography. The highest suPAR quartile (vs. the lowest) had an adjusted odds ratio of 2.66 (95% confidence interval [CI], 1.77-3.99) for AKI and 2.29 (95% CI, 1.71-3.06) for AKI or death at 90 days. Findings were similar in the surgical and critically ill cohorts. The suPAR-overexpressing mice that were given contrast material had greater functional and histologic evidence of AKI than wild-type mice. The suPAR-treated HK-2 cells showed heightened energetic demand and mitochondrial superoxide generation. Pretreatment with an uPAR monoclonal antibody attenuated kidney injury in suPAR-overexpressing mice and normalized bioenergetic changes in HK-2 cells.
Conclusions:
The authors concluded that high suPAR levels were associated with AKI in various clinical and experimental contexts.
Perspective:
This cohort study reports that suPAR was associated with subsequent AKI in several cohorts of patients exposed to intra-arterial contrast material for coronary angiography, who underwent cardiac surgery, or who were critically ill. Furthermore, it appears that suPAR may be directly involved in the pathogenesis of AKI by sensitizing kidney proximal tubules to injury through modulation of cellular bioenergetics and increased oxidative stress. Of note, the absolute suPAR values defining the population with the highest risk of AKI as well as the odds ratios for AKI varied substantially among the patient cohorts in this study (i.e., the coronary angiography, cardiac surgery, and ICU cohorts), which emphasizes that suPAR, as any other biomarker, must be interpreted within specific clinical context. Finally, elevated suPAR levels in patients in the ICU or in patients seen before elective procedures should not be simply viewed as a risk indicator for AKI, but should prompt a thorough investigation for acute or chronic coexisting conditions, which will likely determine the patient’s prognosis.
Clinical Topics: Cardiac Surgery, Diabetes and Cardiometabolic Disease, Dyslipidemia, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Prevention, Cardiac Surgery and Arrhythmias, Lipid Metabolism, Novel Agents, Interventions and Imaging, Angiography, Nuclear Imaging, Stress
Keywords: Acute Kidney Injury, Biomarkers, Cardiac Surgical Procedures, Coronary Angiography, Critical Illness, Intensive Care Units, Kidney Tubules, Proximal, Metabolic Syndrome, Oxidative Stress, Primary Prevention, Reactive Oxygen Species, Receptors, Urokinase Plasminogen Activator, Superoxides, Urokinase-Type Plasminogen Activator
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