Uncovering a 'suPAR' culprit behind kidney injury in COVID-19

Date:
September 24, 2020
Source:
Michigan Medicine - University of Michigan
Summary:
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.



FULL STORY ========================================================================== 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 (University of Michigan) 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." Hayek, an expert on this protein is currently researching how
best to reduce suPAR levels in those people at highest risk.

"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 Du"sseldorf).


========================================================================== Story Source: Materials provided by
Michigan_Medicine_-_University_of_Michigan. Original written by Haley
Otman. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Tariq U. Azam, Husam R. Shadid, Pennelope Blakely, Patrick O'Hayer,
Hanna
Berlin, Michael Pan, Peiyao Zhao, Lili Zhao, Subramaniam
Pennathur, Rodica Pop-Busui, Izzet Altintas, Jens Tingleff,
Marius A. Stauning, Ove Andersen, Maria-Evangelia Adami, Nicky
Solomonidi, Maria Tsilika, Pinkus Tober-Lau, Eleni Arnaoutoglou,
Verena Keitel, Frank Tacke, Athanasios Chalkias, Sven H. Loosen,
Evangelos J. Giamarellos-Bourboulis, Jesper Eugen-Olsen, Jochen
Reiser, Salim S. Hayek. Soluble Urokinase Receptor (SuPAR) in
COVID-19-Related AKI. Journal of the American Society of Nephrology,
2020; ASN.2020060829 DOI: 10.1681/ASN.2020060829 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/09/200924135406.htm

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