Nephrotic Syndrome Disease Activity Predicts Severity of the Associated Hypercoagulopathy

Nephrotic syndrome (NS) is associated with an acquired hypercoagulopathy and strong predilection for life-threatening thrombotic complications. Current anticoagulant prophylaxis guidelines are based upon controversial hypoalbuminemia thresholds. Anticoagulant prophylaxis is thus inconsistently implemented due to a lack of high-grade safety and efficacy data. Development of evidence-based clinical parameters that define thrombosis risk may thus refine safe and effective anticoagulant use. Endogenous thrombin potential (ETP) is a recognized measure of hypercoagulopathy and established predictor of both incident and recurrent thrombosis. This study utilized biorepository samples from a prospective longitudinal cohort study to demonstrate that ETP is proportional to NS disease activity, resulting in multivariable models that are significantly correlated with ETP. The relationship with disease activity was confirmed in a separate cohort. These models revealed that ETP is related to disease activity in a manner dependent on remission status and that proteinuria and hypercholesterolemia exert the strongest influence on ETP. In contrast to prior epidemiology studies, which did not include hypercoagulopathy measures, we found that hypoalbuminemia was less predictive of ETP. These findings are consistent with our previously reported animal model observations and are expected to inform the design of clinical trials that will generate high-grade evidence to guide more effective and safer anticoagulant use and thus reduce life-threatening thrombotic events in patients with NS.