Could suPAR be Missing Link Between CVD and Kidney Disease? 2018 Zipes Keynote Looks at Novel Biomarker

The search for a novel biomarker of cardiovascular disease has led to the promising study of suPAR — soluble urokinase-type plasminogen activator receptor — a signaling protein in blood. This biomarker of inflammation may be strongly associated with both cardiovascular outcomes and chronic kidney disease (CKD).

The study of suPAR and the qualities that make it a strong predictor of renal function in patients with heart disease will be examined today in the Douglas P. Zipes, MD, MACC, Distinguished Young Scientist Keynote. Salim S. Hayek, MD, a fellow in training at Emory University School of Medicine in Atlanta, will explain how his research helped uncover the untapped potential of tracking suPAR levels in patients and what lies ahead.

As a fellow in the clinical investigator track at Emory, Hayek manages the Emory Cardiovascular Biobank, comprising data from a cohort of patients undergoing cardiac catheterization. In this cohort, Hayek and colleagues found that suPAR levels at enrollment were associated with a decline in renal function.

“This was the first evidence of a biomarker that was strongly predictive of a decline in renal function in patients with cardiovascular disease,” says Hayek. Follow-up studies found the same association between suPAR and renal function even in patients with no signs of kidney dysfunction across multiple patient cohorts and ethnicities, he adds.

Cardiology Magazine Image"This was the first evidence of a biomarker that was strongly predictive of a decline in renal function in patients with cardiovascular disease." Salim S. Hayek, MD

Further work has shown suPAR is the first biomarker of incident renal dysfunction in the general population as well as people with cardiovascular disease. This is an improvement over relying on creatinine and proteinuria as markers of kidney damage, because elevations in these are found after kidney damage is present.

suPAR levels are high in patients who have cardiovascular risk factors or heart disease. Specifically, the levels are very high in those who have heart failure and peripheral vascular disease — a population with a high incidence of CKD. The working hypothesis of Hayek and colleagues is that the prolonged exposure to the high levels of suPAR eventually leads to kidney dysfunction, proteinuria and CKD.

Could suPAR be a missing link between cardiovascular disease and kidney disease? Hayek thinks it could be and is working to elucidate this potential link. Testing is underway to determine whether blocking or removing suPAR would improve outcomes in some clinical scenarios.

Other researchers are developing monoclonal antibodies that have shown positive results in mouse models in preventing renal disease and declining renal function. Previous research by other investigators had found a link between suPAR and focal segmental glomerulosclerosis.

“We’re looking at diagnostic trials that include measurement of suPAR levels,” says Hayek. Work is also ongoing regarding risk stratification in kidney disease as well as cardiovascular disease. “This is going to take a few more years, but we feel strongly that within the next five to 10 years we may be able to measure suPAR on a routine basis,” he adds.

The Douglas P. Zipes, MD, MACC, Distinguished Young Scientist Awardee Presentation will take place today from 10:45 a.m. – 12:15 p.m. in Room 307 A.

Keywords: ACC Publications, ACC Scientific Session Newspaper, ACC Annual Scientific Session

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