Global Alliance Forms to Explore suPAR’s Impact on COVID-19 Management

Fri Jun 26 2020

By: Thomas Krarup, ViroGates

suPAR News Vol. 3, p.14-15, June 2020

Salim Hayek specializes in cardiovascular diseases, is a clinical investigator, and serves as a consultant. He gained expertise in translational science, onco-cardiology, preventive cardiology, and cardiac imaging through education and training at the American University of Beirut, the University of Ottawa, and Emory University School of Medicine. His impressive bibliography includes 95 peer-reviewed papers published in top journals like Nature Medicine, Nature Genetics, Circulation, and the New England Journal of Medicine.

Currently, Dr. Hayek is an Assistant Professor in medicine and cardiology at the University of Michigan in Ann Arbor.

His research focuses on understanding the link between kidney and cardiovascular disease and finding new treatments for patients with both conditions. His groundbreaking work, published in the New England Journal of Medicine, shows that suPAR levels are linked to chronic kidney disease (CKD) and acute kidney injury (AKI), playing a role in kidney disease pathogenesis. These findings are significant because high suPAR levels can predict CKD progression in asymptomatic individuals and identify hospital patients at risk for AKI, allowing for early intervention.

Salim S. Hayek, MD, has hypothesized that baseline plasma suPAR levels can predict the severity of COVID-19 outcomes.

Salim S. Hayek, MD

Fig. 1. Hypothesis: the baseline plasma suPAR level can differentiate whether patients with COVID-19 will have a mild or a severe outcome of the infection.

At the COVID-19 crisis onset, Dr. Hayek formed an international hospital consortium to study inflammatory biomarkers like suPAR for COVID-19 patient triaging. Using a REDcap web application, the consortium completed patient data entry by May 10, enrolling over 750 patients, and is preparing a manuscript for submission.

We had the opportunity to talk with Dr. Hayek about the international COVID-19 consortium and his pivotal studies on suPAR.

SuPAR News: Dr. Hayek, thank you for your time. Could you tell us why you initiated an international collaboration to study suPAR and other biomarkers for COVID-19 patient triaging?

“The importance of the multi-center approach is in the validity of the findings, and minimizing the risk of selection bias. International collaborations are even more valuable: if a finding is reproduced across countries and cultures, then it is more likely to be true.”

Asst. Prof. Salim S. Hayek

Dr. Hayek: The importance of the multi-center approach is in the validity of the findings, and minimizing the risk of selection bias. International collaborations are even more valuable: if a finding is reproduced across countries and cultures, then it is more likely to be true.

suPAR News: Which hospitals are involved in the collaboration?

Dr. Hayek: University of Michigan, Ann Arbor, USA; University Hospital Hvidovre, Copenhagen, Denmark; Attikon University Hospital, Athens, Greece; University of Thessaly, Larisa, Greece; University Hospital of Düsseldorf, Düsseldorf, Germany; and Charité de Berlin, Berlin, Germany.

suPAR News: What were the inclusion criteria?

Dr. Hayek: Patients, 18 years or older, who presented to the ED with respiratory symptoms secondary to confirmed COVID-19 and were hospitalized.

suPAR News: What type of data will be presented in the paper to soon be published?

Dr. Hayek: Detailed clinical characteristics, presentation symptoms, kidney function, respiratory status, and details on the in-hospital course and outcomes.

“Patients with high suPAR should be very aggressively managed with risk factor control and lifestyle changes.”

Asst. Prof. Salim S. Hayek

Dr. Hayek emphasizes the significance of a multi-center approach in ensuring the validity of findings and reducing selection bias risks. He highlights the additional value of international collaborations, stating that findings replicated across different countries and cultures are more likely to be true.

When asked about the collaborating hospitals, Dr. Hayek lists several, including the University of Michigan in Ann Arbor, USA; University Hospital Hvidovre in Copenhagen, Denmark; Attikon University Hospital in Athens, Greece; the University of Thessaly in Larisa, Greece; University Hospital of Düsseldorf in Düsseldorf, Germany; and Charité de Berlin in Berlin, Germany.

The inclusion criteria for their study were hospitalized patients aged 18 or older, who came to the emergency department (ED) with respiratory symptoms from confirmed COVID-19.

The upcoming paper will present detailed data on patients’ clinical characteristics, symptoms at presentation, kidney and respiratory status, and information on their in-hospital course and outcomes.

Dr. Hayek asserts the necessity of aggressive management for patients with high suPAR levels, including risk factor control and lifestyle changes, to improve their prognosis.

Transitioning the discussion to nephrology, Dr. Hayek shares his motivation for focusing on kidney disease due to its significant impact on managing and risking cardiovascular disease. He aims to uncover the complex relationship between the two and develop therapies to reduce kidney disease risk in cardiovascular patients.

Highlighting his research, Dr. Hayek mentions a 2015 NEJM paper that found high suPAR levels associated with a future decline in eGFR, potentially leading to CKD. His most recent NEJM paper expands this finding, linking elevated suPAR levels to AKI. He believes this breakthrough could significantly reduce the risk of acute kidney injury in millions undergoing cardiac procedures.

Dr. Hayek advises nephrologists to view high suPAR levels as an indicator of poor long-term outcomes. Although treatments to lower suPAR levels are not yet available, he recommends aggressively managing patients with high suPAR through risk factor control and lifestyle changes.

Asst. Prof. Salim S. Hayek with his team at the Frankel Cardiovascular Center, University of Michigan, Ann Arbor.

Fig. 2. Asst. Prof. Salim S. Hayek with his team at the Frankel Cardiovascular Center, University of Michigan, Ann Arbor

1. Hayek SS et al. Soluble urokinase receptor and chronic kidney disease. N Engl J Med 373;20;1916-25 (2015).
2. Hayek SS et al. Soluble Urokinase Receptor and Acute Kidney Injury. N Engl J Med 382;5;416-426 (2020).

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