Urinary excretion of fatty acid-binding protein 4 is associated with albuminuria and renal dysfunction

Fatty 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.

Subjects 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.

In 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.

Urinary 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.