Urinary fatty acid binding protein 3 (uFABP3) is a potential biomarker for peripheral arterial disease

Abstract

Plasma levels of fatty acid binding protein 3 (pFABP3) are elevated in patients with peripheral artery disease (PAD). Since the kidney filters FABP3 from circulation, we investigated whether urinary fatty acid binding protein 3 (uFABP3) is associated with PAD, and also explored its potential as a diagnostic biomarker for this disease state. A total of 130 patients were recruited from outpatient clinics at St. Michael's Hospital, comprising of 65 patients with PAD and 65 patients without PAD (non-PAD). Levels of uFABP3 normalized for urine creatinine (uFABP3/uCr) were 1.7-folds higher in patients with PAD [median (IQR) 4.41 (2.79-8.08)] compared with non-PAD controls [median (IQR) 2.49 (1.78-3.12), p-value = 0.001]. Subgroup analysis demonstrated no significant effect of cardiovascular risk factors (age, sex, hypertension, hypercholesteremia, diabetes and smoking) on uFABP3/uCr in both PAD and non-PAD patients. Spearmen correlation studies demonstrated a significant negative correlation between uFABP3/uCr and ABI (ρ = - 0.436; p-value = 0.001). Regression analysis demonstrated that uFABP3/Cr levels were associated with PAD independently of age, sex, hypercholesterolemia, smoking, prior history of coronary arterial disease and Estimated Glomerular Filtration rate (eGFR) [odds ratio: 2.34 (95% confidence interval: 1.47-3.75) p-value < 0.001]. Lastly, receiver operator curve (ROC) analysis demonstrated unadjusted area under the curve (AUC) for uFABP3/Cr of 0.79, which improved to 0.86 after adjusting for eGFR, age, hypercholesteremia, smoking and diabetes. In conclusion, our results demonstrate a strong association between uFABP3/Cr and PAD and suggest the potential of uFABP3/Cr in identifying patients with PAD.

Figure 1

Boxplot illustrating the levels of normalized uFABP3/uCr among non-PAD controls (n = 65) and PAD patients stratified based on their ABI values (mild PAD: 0.89–0.75, n = 11; moderate PAD: 0.74–0.50, n = 29; severe PAD: < 0.50, n = 25). Significant difference in median uFABP3/uCr levels was noted between the moderate and severe PAD subgroups compared to non-PAD group, (p-value < 0.001). Values displayed in figure represents median uFABP3/uCr levels values in each subgroup. * p-value < 0.05 compared to non-PAD group.

Figure 2

Receiver operating characteristic (ROC) curves of uFABP3/uCr for distinguishing patients with peripheral arterial disease (PAD, n = 65) from patients without PAD (non-PAD, n = 65) in an unadjusted model (solid line) and an adjusted model (dashed line). The area under the curve (AUC) and the 95% confidence intervals for uFABP3/uCr improved from 0.79 (95%: 0.71–0.87) to 0.86 (95%: 0.80–0.92) after adjusting for eGFR, age, hypercholesteremia, smoking and diabetes.