Elevated levels of soluble urokinase plasminogen activator receptor (suPAR), a signaling glycoprotein expressed in immune and other cells, may predispose patients to acute kidney injury (AKI), new findings published in the New England Journal of Medicine suggest.

Salim Hayek, MD, of the University of Michigan in Ann Arbor, and colleagues assessed 3 cohorts at risk for AKI: 3827 patients having coronary angiography with contrast material, 250 undergoing cardiac surgery, and 692 admitted to the intensive care unit (ICU).

AKI developed in 8% of the coronary angiography cohort, the team reported. Elevated suPAR was associated with increased risks of AKI within the first 7 days. In a fully adjusted model, AKI risk was 1.7-, 1.9-, and 2.7-fold higher for patients in second, third, and fourth quartiles (2475 to 3198, 3199 to 4183, and 4184 pg/mL or higher) compared with those in the first quartile (less than 2475 pg/mL). Patients in the fourth quartile also had a 2.3-fold higher risk for AKI or death within 90 days.

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Findings were similar in the surgical and ICU cohorts, although they received no contrast material. AKI risk increased with the suPAR quartiles, variably defined. For example, AKI risk increased 3.5 to 4.0-fold in suPAR quartile 4 compared with quartile 1.

The investigators also conducted experiments in mice and human cells and found that suPAR-overexpressing mice given contrast material had greater functional and histologic evidence of AKI than wild-type mice, they reported. Human kidney proximal tubular (HK-2) cells treated with suPAR showed increased energy demand and mitochondrial superoxide generation.

While promising, the clinical interpretation of elevated circulating suPAR levels remains challenging, Frank Tacke, MD, PhD, of Charité University Medicine Berlin, noted in an accompanying editorial. Studies also have associated suPAR with inflammatory processes or liver failure.

“Thus, elevated suPAR levels in patients in the ICU or in patients seen before elective procedures (e.g., angiography or surgery) should not be simply viewed as a risk indicator for acute kidney injury but rather should prompt a thorough investigation for acute or chronic coexisting conditions, which will ultimately determine the patient’s prognosis,” Dr Tacke commented.

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Hayek SS, Leaf DE, Tahhan AS, et al. Soluble urokinase receptor and acute kidney injury. N Engl J Med. 2020;382:416-426. doi: 10.1056/NEJMoa1911481

Tacke F. Risk prediction for acute kidney injury—Super important, no suPAR easy? N Engl J Med. 2020;382:470-472. doi: 10.1056/NEJMe1916796