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

Abstract

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 patient-years (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 serum albumin levels.

Keywords: cohort; nephrotic syndrome; risk factors; serum albumin; venous thromboembolism.

FIGURE 1

Kaplan–Meier curves showing the association between serum albumin (Alb) categories and risk of incident venous thromboembolic events (VTE) for 7037 US Veteran patients with nephrotic syndrome.

FIGURE 2

Association of serum albumin level with risk of incident venous thromboembolic events (VTE) in unadjusted Cox regression models in 7037 US Veteran patients with nephrotic syndrome.

FIGURE 3

Association of serum albumin categories with risk of incident venous thromboembolic events in unadjusted and adjusted Cox regression models in 7037 US Veteran patients with nephrotic syndrome. Models were adjusted for the following confounders: Model 1: age, gender, race/ethnicity; Model 2: Model 1 variables, baseline eGFR, body mass index and comorbidities measured with Charlson comorbidity index; Model 3: Model 2 variables and use of anticoagulants. CI, confidence interval.

FIGURE 4

Association of serum albumin categories with risk of incident venous thromboembolic events in fully adjusted Cox regression models in patients with different causes of nephrotic syndrome. Models were adjusted for age, gender, race/ethnicity, baseline estimated glomerular filtration rate, body mass index and comorbidities measured with Charlson comorbidity index and use of anticoagulants. CI, confidence interval; FSGS, focal segmental glomerulosclerosis; MCD, minimal change disease; MPGN, membranoproliferative glomerulonephritis.