High soluble urokinase plasminogen activator receptor levels linked with AKI
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High soluble urokinase plasminogen activator receptor levels were associated with acute kidney injury and may be a pathogenic factor for the condition, according to a study.
“This study showed that [soluble urokinase plasminogen activator receptor] suPAR was associated with subsequent acute kidney injury in several cohorts,” Jochen Reiser, MD, PhD, professor and chair of medicine at RUSH University Medical Center, and colleagues wrote. “Concurrently, we obtained experimental evidence that suPAR may be directly involved in the pathogenesis of acute kidney injury by sensitizing kidney proximal tubules to injury through modulation of cellular bioenergetics and increased oxidative stress.”
Researchers analyzed the association between suPAR levels and postprocedural AKI in two prospective cohorts of patients who underwent coronary angiography and cardiac surgery. One cohort included 2,752 patients from three Emory Healthcare sites in Atlanta from 2003 and 2015 and the other cohort enrolled 1,075 patients from Massachusetts General Hospital in Boston from 2008 and 2011. Risk of AKI at 7 days was assessed as the primary outcome and AKI or death at 90 days was assessed as the secondary outcome.
Researchers also performed experimental animal studies using a monoclonal antibody to urokinase plasminogen activator receptor as a therapeutic strategy to reduce AKI in transgenic mice.
Results showed postprocedural AKI developed in 318 (8%) patients, with a mean increase in the creatinine level of 0.44+0.54 mg per deciliter in patients with AKI compared to 0.01+0.22 in those without AKI. Most AKI cases within 7 days after angiography were mild, with 98% having Kidney Disease: Improving Global Outcomes stage 1; 28 patients having KDIGO stage 2; and three patients having KDIGO stage 3 AKI.
After coronary angiography, the AKI incident rate was 14% in the highest suPAR quartile and 4% in the lowest quartile. There was a strong association between suPAR level and postprocedural AKI and the association between the suPAR level and the combined outcome of AKI or death from any cause at 90 days.
Mice in the experimental study that were given contrast material had greater functional and histological evidence of AKI than wild-type mice. The chronically elevated suPAR levels sensitized the kidney to acute injury, according to researchers.
“High suPAR levels were associated with incident acute kidney injury in several patient cohorts,” the researchers wrote. “The experimental models used here suggest that suPAR may be a pathogenic factor in acute kidney injury.” – by Erin T. Welsh
Disclosures: Resier reports receiving payment or services by NIH; has been a paid consultant for Biomarin, Astellas, Massachusetts General Hospital, Genenetech, Up to Date, Merck, Inceptionsci, GLG, Arch Ventures and Cytogenetics; received grants from the NIH, Nephcure and Thermo BCT; and is co-founder and equity holder in TRISAQ.
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