Indicators of Blood Clot Potential Directly Relate to Nephrotic Syndrome Severity

Indicators of Blood Clot Potential Directly Relate to Nephrotic Syndrome Severity 150 150 Katie Brind'Amour, PhD, MS, CHES

Researchers in the NEPTUNE network and collaborators at Nationwide Children’s Hospital have confirmed their preclinical studies demonstrating a direct correlation between the severity of disease and prothrombotic biomarkers in patients with nephrotic syndrome.

Nephrotic syndrome (NS) dramatically increases the risk of a life-threatening blood clot, but until recently, clinicians have had no reasonable biomarker to directly understand clotting potential based on NS disease status or traditional NS clinical tests.

“We are trying to understand which nephrotic syndrome patients are most likely to benefit from prophylactic anticoagulant therapy. Because these medications carry a substantial risk of bleeding complications, we don’t want to  prescribe them to all patients, but only those at highest risk for blood clots,” says Bryce A. Kerlin, MD, a pediatric hematologist and principal investigator in the Center for Clinical & Translational Research in the Abigail Wexner Research Institute at Nationwide Children’s Hospital.

Dr. Kerlin led a prior study searching for possible biomarkers in an animal model of NS, published in the Journal of the American Society of Nephrology in 2015. “We sorted out how to correlate clotting parameters with NS disease markers in animals, and in this latest study, we were able to show essentially the same relationship was true in human patients — which means we have potentially valuable biomarkers,” he says. “Now we need to figure out if they really predict who is going to develop a clotting complication.”

Although a low-grade evidence guideline exists, suggesting that hypoalbuminemia may be used to predict blood clot risk, there was no clear mechanistic relationship between this common NS clinical indicator and thrombotic potential. The recent research, published in Thrombosis Research, used clinical test results and thrombin generation assays from biorepository plasma samples from the longitudinal NS study known as NEPTUNE, as well as from a prospective cohort of incident NS patients from Nationwide Children’s and The Ohio State University Wexner Medical Center.

The team found that endogenous thrombin potential — a hypercoagulopathy biomarker used in other populations to effectively predict blood clot risk — was strongly associated with NS severity, as defined by disease indicators used in routine NS clinical monitoring: proteinuria, hypercholesterolemia and low serum albumin.

“It has been known for many decades that both children and adults with NS are at dramatically increased risk for blood clots, a rare but potentially deadly complication of NS,” says William E. Smoyer, MD, pediatric nephrologist and vice president and director for the Center for Clinical and Translational Research. “The current findings will significantly improve our ability to identify those NS patients at the highest risk for clotting, who would benefit most from prophylactic treatment with anticoagulants to prevent such clots. Broad use of such anticoagulant medications in all patients with NS has historically been discouraged among nephrologists, due to the inherent risks for bleeding when using anticoagulants. However, these findings now enable us to better identify those patients in whom the risk-benefit ratio more clearly warrants preventative anticoagulation.”

Nephrologists and hematologists have also traditionally had a difficult time determining when it is safe to stop anticoagulant therapy once it is started. But the recent research also revealed that if NS goes into remission, hypercoagulation diminishes, meaning patients can stop taking an anticoagulant.

“Once disease is in remission, the clotting risk doesn’t linger,” says Dr. Kerlin. “Moving forward, we’d like to develop a risk algorithm that nephrologists can use over time as they see patients, so that they know when to start and stop anticoagulants based on thrombosis risk as predicted by the patient’s NS disease markers. We’re trying to give them the tools to make evidenced-based clinical decisions that will help to prevent these life-threatening blood clots.”



  1. Kerlin BA, Waller AP, Sharma R, Chanley MA, Nieman MT, Smoyer WE. Disease severity correlates with thrombotic capacity in experimental nephrotic syndrome. Journal of the American Society of Nephrology. 2015 Dec;26(12):3009-19.
  2. Waller AP, Troost JP, Parikh SV, Wolfgang KJ, Rovin BH, Nieman MT, Smoyer WE, Kretzler M, Kerlin BA; NEPTUNE Investigators. Nephrotic syndrome disease activity is proportional to its associated hypercoagulopathy. Thrombosis Research. 2021 Feb 16;201:50-59.


About the author

Katherine (Katie) Brind’Amour is a freelance medical and health science writer based in Pennsylvania. She has written about nearly every therapeutic area for patients, doctors and the general public. Dr. Brind’Amour specializes in health literacy and patient education. She completed her BS and MS degrees in Biology at Arizona State University and her PhD in Health Services Management and Policy at The Ohio State University. She is a Certified Health Education Specialist and is interested in health promotion via health programs and the communication of medical information.