Risk of Arterial Thromboembolism, Venous Thromboembolism, and Bleeding in Patients with Nephrotic Syndrome: A Population-Based Cohort Study.

BACKGROUND: Although venous thromboembolism is a well-known complication of nephrotic syndrome, the long-term absolute and relative risks of arterial thromboembolism, venous thromboembolism, and bleeding in adults with nephrotic syndrome remain unclarified. METHODS: In this matched cohort study, we identified every adult with first-time recorded nephrotic syndrome from admissions, outpatient clinics, or emergency department visits in Denmark during 1995-2018. Each patient was matched by age and sex with 10 individuals from the general population. We estimated the 10-year cumulative risks of recorded arterial thromboembolism, venous thromboembolism, and bleeding accounting for the competing risk of death. Using Cox models, we computed crude and adjusted hazard ratios (HRs) of the outcomes in patients with nephrotic syndrome versus comparators. RESULTS: Among 3967 adults with first-time nephrotic syndrome, the 1-year risk of arterial thromboembolism was 4.2% (95% confidence interval [CI] 3.6-4.8), of venous thromboembolism was 2.8% (95% CI 2.3-3.3), and of bleeding was 5.2% (95% CI 4.5-5.9). The 10-year risk of arterial thromboembolism was 14.0% (95% CI 12.8-15.2), of venous thromboembolism 7.7% (95% CI 6.8-8.6), and of bleeding 17.0% (95% CI 15.7-18.3), with highest risks of ischemic stroke (8.1%), myocardial infarction (6.0%), and gastrointestinal bleeding (8.2%). During the first year, patients with nephrotic syndrome had increased rates of both arterial thromboembolism (adjusted HR [HRadj] = 3.11 [95% CI 2.60-3.73]), venous thromboembolism (HRadj = 7.11 [5.49-9.19]), and bleeding (HRadj = 4.02 [3.40-4.75]) compared with the general population comparators after adjusting for confounders. CONCLUSION: Adults with nephrotic syndrome have a high risk of arterial thromboembolism, venous thromboembolism, and bleeding compared with the general population. The mechanisms and consequences of this needs to be clarified.