Glomerular expression and urinary excretion of fatty acid-binding protein 4 in IgA nephropathy

Background Fatty acid-binding protein 4 (FABP4) is secreted from adipocytes and macrophages in adipose tissue and acts as an adipokine. It has recently been reported that FABP4, but not liver-type FABP (L-FABP/FABP1), is also expressed in injured glomerular endothelial cells and infiltrating macrophages in the glomerulus and that urinary FABP4 (U-FABP4) is associated with proteinuria and kidney function impairment in nephrotic patients. However, the link between glomerular FABP4 and U-FABP4 has not been fully addressed in IgA nephropathy (IgAN). Methods We investigated the involvement of FABP4 in human and mouse IgAN. Results In patients with IgAN (n = 23), the ratio of FABP4-positive area to total area within glomeruli (G-FABP4-Area) and U-FABP4 were positively correlated with proteinuria and were negatively correlated with eGFR. In 4-28-week-old male grouped ddY mice, a spontaneous IgAN-prone mouse model, FABP4 was detected in glomerular endothelial cells and macrophages, and G-FABP4-Area was positively correlated with urinary albumin-to-creatinine ratio (r = 0.957, P < 0.001). Endoplasmic reticulum stress markers were detected in glomeruli of human and mouse IgAN. In human renal glomerular endothelial cells, FABP4 was induced by treatment with vascular endothelial growth factor and was secreted from the cells. Treatment of human renal glomerular endothelial cells or mouse podocytes with palmitate-bound recombinant FABP4 significantly increased gene expression of inflammatory cytokines and endoplasmic reticulum stress markers, and the effects of FABP4 in podocytes were attenuated in the presence of an anti-FABP4 antibody. Conclusion FABP4 in the glomerulus contributes to proteinuria in IgAN, and U-FABP4 level is a useful surrogate biomarker for glomerular damage in IgAN.

Automated summary

The expression of fatty acid-binding protein 4 (FABP4) is increased in the glomerulus of patients with IgA nephropathy (IgAN), and urinary FABP4 level is associated with glomerular FABP4 expression. These findings suggest that glomerular FABP4 contributes to proteinuria in IgAN, and urinary FABP4 level can serve as a biomarker for evaluating glomerular damage.