Association of serum albumin level and venous thromboembolic events in a large cohort of patients with nephrotic syndrome

Background. Prior small studies have suggested an association between low serum albumin and increased risk of venous thromboembolic (VTE) events in patients with nephrotic syndrome (NS). Methods. From a nationally representative prospective cohort of over 3 million US veterans with baseline estimated glomerular filtration rate (eGFR) >= 60 mL/min/1.73 m(2), we identified 7037 patients with NS based on ICD-9 codes. Association between serum albumin and risk of incident VTE was assessed using Cox regression analysis with adjustments for age, gender, race, comorbidities, eGFR, body mass index and anticoagulant treatment. Results. Mean age was 57 +/- 11 years, patients were 96% male, 32% African-American and 60% diabetic. There were a total of 158 VTE events over a median follow-up of 8.1 years; 16 events [absolute event rate (AER) 4.1%, event rate 8.5/1000 patientyears (PY)] in patients with albumin < 2.5 g/dL, 18 events (AER 3.4%, event rate 5.7/1000 patient-years) in patients with albumin 2.5-2.99 g/dL, 89 events (AER 2.5%, event rate 3.4/1000 patient-years) in patients with albumin 3-3.99 g/dL and 35 events (AER 1.4%, event rate 1.9/1000 patient-years) in patients with albumin >= 4 g/dL. Compared with patients with albumin >= 4 g/dL, those with albumin levels of 3-3.99 g/dL [adjusted hazard ratio (HR): 1.51, 95% confidence interval (CI): 1.01-2.26], 2.5-2.99 g/dL (HR: 2.24, 95% CI: 1.24-4.05) and < 2.5 g/dL (HR: 2.79, 95% CI: 1.45-5.37) experienced a linearly higher risk of VTE events. Conclusions. Lower serum albumin is a strong independent predictor for VTE events in NS. The risk increases proportionately with declining albumin levels. Clinical trials are needed to determine benefit of prophylactic anticoagulation in NS patients with moderately lower serumalbumin levels.