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suPAR’s role in COVID-19: a new international multi-center collaboration has emerged

Fri Jun 26 2020

By: Thomas Krarup, ViroGates

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

Salim Hayek (Fig. 1) is a specialist in cardiovascular diseases, a clinical investigator and consultant. His education and training at the American University of Beirut, the University of Ottowa and at the Emory University School of Medicine have allowed mastery in translational science and clinical areas such as onco-cardiology, preventive cardiology, and cardiac imaging, all described in a stunning bibliography of currently 95 peer-reviewed papers. Many of those are published in some of the World’s best journals including Nature Medicine, Nature Genetics, Circulation, and the New England Journal of Medicine.

Presently, Dr. Hayek holds a position as Asst. Prof. in medicine and cardiology at the University of Michigan in Ann Arbor (Fig. 2).

Overall, Dr. Hayek’s research interests are centered on a better understanding of the interplay between kidney and cardiovascular disease, and on identifying new therapeutic strategies for the ever-growing population of patients with concomitant cardiovascular and kidney disease. Two groundbreaking contributions, both published with co-authors in the New England Journal of Medicine, provide evidence that suPAR is independently associated with incident chronic kidney disease (CKD)1 as well as with acute kidney injury (AKI)2, and appears to be directly involved in the pathogenesis of kidney disease. The significance of these findings is high: an elevated suPAR level can help predict progression to CKD in asymptomatic and hence, seemingly healthy persons at a time where renal function is still intact, which will allow early intervention. Likewise, amongst hospital-admitted patients, the suPAR level can help predicting who may be at risk for developing AKI.

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 onset of the COVID-19 crisis, Dr. Hayek established an international consortium of hospitals investigating the role and usefulness of a number of inflammatory biomarkers including suPAR for triaging of patients with COVID-19. Using a REDcap web application, the finishing line for completion of patient data entry was May 10. By then, the participating hospitals had enrolled more than 750 patients. Also, in parallel, a manuscript was prepared, which the consortium hopes to submit very soon.

We have had the great pleasure of speaking with Dr. Hayek about the international COVID-19 consortium. Also, some questions were asked related to the two cornerstone papers already mentioned, were suPAR has a prominent role.

SuPAR News: Dr. Hayek, thanks much for finding the time to speaking with us. Will you expand on why you decided to establish an international collaboration evaluating suPAR and other biomarkers for triaging of patients suspected for COVID-19?

“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

suPAR News: We would like to change the discussion from COVID-19 to nephrology. Which event is the reason you originally became interested in kidney disease?

Dr. Hayek: Kidney disease represents a major challenge in the management and risk of cardiovascular disease. As a cardiologist and clinical investigator, I have taken up the challenge to decipher the poorly understood link between both diseases and devise therapies to decrease the risk of kidney disease in patients with cardiovascular issues.

suPAR News: Your 2015 NEJM-paper presents evidence that elevated suPAR is associated with future decline in eGFR, which potentially leads to CKD. In your most recent NEJM-paper, the finding is broadened to also associate elevated suPAR with AKI. How do you believe your research will benefit patients in the future?

Dr. Hayek: There has been little progress in the prevention and treatment of kidney injury and chronic kidney disease over the past half a century. This study represents a breakthrough in the field, as it identifies suPAR as a novel pathogenic and therapeutic target, through which we may be able to dramatically reduce the procedural risks of acute kidney injury in millions of patients undergoing cardiac surgery or coronary angiography.

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

suPAR News: How will you suggest nephrologists facing kidney patients at the hospitals today should apply suPAR in their clinical decision making?

Dr. Hayek: High suPAR levels is the hallmark of a patient with poor long-term outcomes. While therapies to reduce suPAR levels are not yet available, patients with high suPAR should be very aggressively managed with risk factor control and lifestyle changes.

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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