Serum Fatty Acid-Binding Protein 4 Is a Predictor of Cardiovascular Events in End-Stage Renal Disease

Abstract

BackgroundFatty acid-binding protein 4 (FABP4/A-FABP/aP2), a lipid chaperone, is expressed in both adipocytes and macrophages. Recent studies have shown that FABP4 is secreted from adipocytes and that FABP4 level is associated with obesity, insulin resistance, and atherosclerosis. However, little is known about the impact of FABP4 concentrations on prognosis. We tested the hypothesis that FABP4 level predicts prognosis of patients with end-stage renal disease (ESRD), a group at high risk for atherosclerosis-associated morbidity and mortality.Methods and ResultsBiochemical markers including FABP4 were determined in 61 ESRD patients on chronic hemodialysis (HD). Serum FABP4 level in females (404.2±30.5 ng/ml) was significantly higher than that in males (315.8±30.0 ng/ml), and the levels in ESRD patients were about 20-times higher than those in age-, gender- and body mass index (BMI)-matched control subjects with normal renal function. FABP4 level was decreased by 57.2% after HD and was positively correlated with blood pressure, BMI, and levels of lipids and insulin. Multiple regression analysis indicated that HD duration, BMI, and triglycerides level were independent determinants for FABP4 level. ESRD patients with high FABP4 levels had higher cardiovascular mortality during the 7-year follow-up period. Cox proportional hazard regression analysis showed that logarithmically transformed FABP4 level was an independent predictor of cardiovascular death adjusted for age, gender, HD duration, BMI, and triglycerides level (hazard ratio, 7.75; 95% CI, 1.05–25.31).ConclusionThese findings suggest that FABP4 level, being related to adiposity and metabolic disorders, is a novel predictor of cardiovascular mortality in ESRD.

Circulating Fatty Acid-Binding Protein 4 Concentration Predicts the Progression of Carotid Atherosclerosis in a General Population Without Medication

“…The serum FABP4 level has also been reported to predict long-term cardiovascular events. [16][17][18] Reduction of the FABP4 level would be a novel therapeutic strategy for preventing the development of atherosclerosis and reducing the incidence of atherosclerotic cardiovascular disease. However, it is unclear whether FABP4 acts by an intracellular signaling mechanism via unidentified receptors, though it is a potential adipokine, an adipocyte-derived bioactive molecule.…”

Post-weaning high-fat diet accelerates kidney injury, but not hypertension programmed by maternal diabetes

“…For example, intrarenal CD36 has been identified as a novel mediator in renal diseases associated with proteinuria and renal dysfunction (35). The elevated level of serum/plasma/urinary Fabp4 is considered a predictor or biomarker for renal dysfunction in diabetes and cardiovascular diseases (23)(24)(25)(26)(27). Hence, we further hypothesized that these affected IUGR offspring fed with HFD would develop metabolic perturbations and kidney injury in adulthood that might be associated with alterations of both renal CD36 and Fabp4 gene expression.…”

“…Emerging evidence suggested that CD36 (19)(20)(21)(22) and Fabp4 (23)(24)(25)(26)(27) are highly implicated in the pathogenesis of HFDinduced cell damage. For example, intrarenal CD36 has been identified as a novel mediator in renal diseases associated with proteinuria and renal dysfunction (35).…”

“…CD36 (19)(20)(21)(22) and fatty acid-binding protein 4 (Fabp4) (23)(24)(25)(26)(27) may mediate chronic inflammation, insulin resistance, oxidant stress, and fibrosis involved in proatherogenic hyperlipidemic states such as obesity. In this study, we followed these affected IUGR offspring from 4 to 20 wk of age and compared the metabolic impacts of post-weaning diet (HFD vs. normal diet (ND)) on handling of lipoproteins, hypertension, and renal function.…”

Reduction of serum FABP4 level by sitagliptin, a DPP-4 inhibitor, in patients with type 2 diabetes mellitus

“…Furthermore, elevated serum concentration of FABP4 has been shown to be associated with obesity, insulin resistance, type 2 diabetes mellitus, hypertension, cardiac dysfunction, renal dysfunction, dyslipidemia, atherosclerosis, and cardiovascular events ( 8,(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24). However, little is known about the modulation of serum FABP4 level by therapeutic drugs including antidiabetic agents except for thiazolidinedione ( 25 ).…”