Uncovering a ‘suPAR’ culprit behind kidney injury in COVID-19
A new observational study finds patients in the hospital for COVID-19 have high levels of soluble urokinase receptor (suPAR), an immune-derived pathogenic protein that is strongly predictive of kidney injury.
Kidney injury is a dreaded complication in patients hospitalized for COVID-19, with more than a third of patients ending up in need of dialysis. Patients with COVID-19-related kidney injury are also at much higher risk of death.
“We don’t known exactly why patients with severe COVID-19 have a high rate of kidney injury,” says Salim Hayek, M.D., a cardiologist at the Michigan Medicine Frankel Cardiovascular Center and senior author of a new observational study.” It is, however, becoming clearer that a hyperactive immune system plays a major role in the morbidity of COVID-19, including kidney-related complications.”
In the multi-center study published in the Journal of the American Society of Nephrology, Hayek and an international team of experts report that levels of a protein in blood produced by immune cells and known to be involved in causing kidney disease are very high in patients hospitalized for COVID-19 and strongly predictive of kidney injury.
The research team tested soluble urokinase plasminogen activator receptor (suPAR) levels of 352 study participants when they were admitted to the hospital for COVID-19 infection.
A quarter of the participants developed acute kidney injury while hospitalized, and their median suPAR levels were more than 60% higher than those of the rest of the participants. The risk of needing dialysis was increased 20-fold in patients with the highest suPAR levels. Overall, median suPAR levels for these study participants hospitalized with severe COVID-19 were almost three times higher than levels of healthy people.
“SuPAR is an immune-derived circulating factor we’ve seen contribute to kidney injury in thousands of patients,” says Jochen Reiser, M.D., Ph.D., a professor of medicine at Rush University and expert in the biology of suPAR. “RNA viruses such as HIV and SARS-CoV-2 elicit a suPAR response of the innate immune system leading to a rise in blood suPAR levels. If there is a hyperinflammatory suPAR response, kidney cells may be damaged.”
Study author Subramaniam Pennathur, M.D., a professor of nephrology at Michigan Medicine, says identifying suPAR levels at hospital admission as a strong predictor for AKI during the hospitalization has important implications for future care.
“For example, obtaining suPAR levels may allow us to risk-stratify, i.e., identify high risk patients early, and institute appropriate preventive treatment, thereby reducing AKI risk and improving COVID-19 outcomes,” he says. “Second, therapies aimed at interrupting suPAR pathway may also be explored for preventative as well as a therapeutic option for COVID-19 AKI.”
“We’re preparing to launch the first clinical trial targeting suPAR to prevent COVID-19 related kidney injury, and by doing so hope to alleviate the burden of kidney disease in both COVID-19 and non-COVID-19 patients with high suPAR levels,” he says.
Additional authors include Tariq Azam, Husam Shadid, Pennelope Blakeley, Patrick O'Hayer, Hanna Berlin, Michael Pan, Peiyao Zhao, Lili Zhao and Rodica Pop-Busui (Michigan Medicine); Izzet Altintas, Jens Tingleff, Marius Stauning, Ove Andersen and Jesper Eugen-Olisen (Copenhagen University Hospital); Maria-Evangelia Adami, Nicky Solomonidi, Maria Tsilika and Evangelos Giamarellos-Bourboulis (National and Kapodistrian University of Athens); Pinkus Tober-Lau and Frank Tacke (Charite Universitatsmedizin Berlin); Eleni Arnaoutoglou and Athanasios Chalkias (University of Thessaly) and Verena Keitel and Sven Loosen (University Hospital Düsseldorf).
Paper cited: “Soluble Urokinase Receptor in COVID-19 related Acute Kidney Injury,” Journal of the American Society of Nephrology. DOI: 10.1681/ASN.2020060829