Abstract
BackgroundFatty acid-binding protein 4 (FABP4/A-FABP/aP2) is expressed in not only adipocytes and macrophages but also peritubular capillaries in the normal kidney. We recently demonstrated that ectopic expression of FABP4, but not FABP1 known as liver FABP (L-FABP), in the glomerulus is associated with progression of proteinuria and renal dysfunction. However, urinary excretion of FABP4 has not been investigated.MethodsSubjects who participated in the Tanno-Sobetsu Study, a study with a population-based cohort design, in 2011 (n = 392, male/female: 166/226) were enrolled. Urinary FABP4 (U-FABP4) and urinary albumin-to-creatinine ratio (UACR) were measured. Change in estimated glomerular filtration rate (eGFR) was followed up one year later.ResultsIn 93 (23.7%) of the 392 subjects, U-FABP4 level was below the sensitivity of the assay. Subjects with undetectable U-FABP4 were younger and had lower UACR and higher eGFR levels than subjects with measurable U-FABP4. U-FABP4 level was positively correlated with age, systolic blood pressure and levels of serum FABP4 (S-FABP4), triglycerides, hemoglobin A1c (HbA1c), urinary FABP1 (U-FABP1) and UACR (r = 0.360, p<0.001). Age, S-FABP4, U-FABP1 and UACR were independent predictors of U-FABP4. On the other hand, systolic blood pressure, HbA1c and U-FABP4 were independently correlated with UACR. Reduction in eGFR after one year was significantly larger in a group with the highest tertile of baseline U-FABP4 than a group with the lowest tertile.ConclusionsUrinary FABP4 level is independently correlated with level of albuminuria and possibly predicts yearly decline of eGFR. U-FABP4 would be a novel biomarker of glomerular damage.
Highlights
Fatty acid-binding proteins (FABPs) are proteins of about 14–15 kDa in size that can reversibly bind to hydrophobic ligands, such as long chain fatty acids, with high affinity and coordinate lipid responses in cells [1, 2]
We recently demonstrated that ectopic expression of FABP4, but not FABP1 known as liver FABP (L-FABP), in the glomerulus is associated with progression of proteinuria and renal dysfunction
In 93 (23.7%) of the 392 subjects, Urinary FABP4 (U-FABP4) level was below the sensitivity of the assay
Summary
Fatty acid-binding proteins (FABPs) are proteins of about 14–15 kDa in size that can reversibly bind to hydrophobic ligands, such as long chain fatty acids, with high affinity and coordinate lipid responses in cells [1, 2]. Among FABPs, FABP1, known as liver FABP (L-FABP), is expressed in proximal tubular epithelial cells in the kidney [3]. It has been reported that urinary FABP1 reflects damage of proximal tubular epithelial cells [4, 5] and predicts progression of renal dysfunction [6, 7]. Recent studies showed that FABP4 is one of the novel adipocyte-derived bioactive molecules referred to as adipokines [13] and that elevated circulating FABP4 level is associated with obesity, insulin resistance, hypertension, cardiac dysfunction and atherosclerosis [14,15,16,17,18,19,20]. Subjects with undetectable U-FABP4 were younger and had lower UACR and higher eGFR levels than subjects with measurable U-FABP4. Reduction in eGFR after one year was significantly larger in a group with the highest tertile of baseline U-FABP4 than a group with the lowest tertile
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