Significance of urinary fatty acid-binding protein 4 level as a possible biomarker for the identification of minimal change disease in patents with nephrotic-range proteinuria

Abstract

Background Fatty acid-binding protein 4 (FABP4), but not FABP1 (liver-type FABP), is ectopically induced in injured glomerular endothelial cells, and urinary FABP4 (U-FABP4) level is associated with proteinuria and renal dysfunction in a general population. Methods The clinical significance of U-FABP4 was investigated in 81 patients (male/female: 43/38, age: 57 ± 17 years) who underwent kidney biopsy. Results U-FABP4 was negatively correlated with estimated glomerular filtration rate (eGFR) (r = − 0.56, P < 0.01) and was positively correlated with age, blood pressure, triglycerides, proteinuria (r = 0.58, P < 0.01), plasma FABP4 and urinary FABP1 (U-FABP1) (r = 0.52, P < 0.01). Multivariable regression analysis showed that eGFR, proteinuria and U-FABP1 were independent predictors of U-FABP4. The level of U-FABP4, but not that of proteinuria, eGFR or U-FABP1, in minimal change nephrotic syndrome (MCNS) was significantly lower than the level in membranous nephropathy (MN) and that in diabetic nephropathy. Receiver operating characteristic curve analysis indicated that U-FABP4 level ≤ 0.78 μg/gCr predicted MCNS in patients who had nephrotic-range proteinuria with a high level of accuracy. When divided by the median value of U-FABP4 at baseline in 33 of the 81 patients who could be followed up, the yearly change (post–pre) in eGFR in the low U-FABP4 group was significantly greater than that in the high U-FABP4 group (median: 11.0 vs. -5.0 mL/min/1.73m2/year). Conclusions U-FABP4 level is independently associated with proteinuria and renal dysfunction in patients with glomerular kidney disease. A low U-FABP4 level may predict MCNS in patients with nephrotic syndrome and would be a useful biomarker for differential diagnosis of MCNS and MN, which are common causes of nephrotic syndrome.

Urinary FABP1 is a biomarker for impaired proximal tubular protein reabsorption and is synergistically enhanced by concurrent liver injury

“…and liver‐specific injury by DT‐R/DT system) (Figures 1B–D , 5C , and 6C ). Consistently, in patients with minimal change nephrotic syndrome or minor glomerular abnormalities, urinary FABP1 levels do not increase despite a marked increase in urinary albumin [ 28 , 29 ]. These observations reinforce our argument that a large amount of filtered FABP1 is efficiently reabsorbed in PTECs unless proximal tubular endocytosis is impaired (Figure 6E ).…”

“…Some studies have shown that urinary FABP1 levels are concomitantly increased with markers of hepatic injury (aspartate aminotransferase, AST, and alanine aminotransferase, ALT) and hypoperfusion (lactate) but not serum creatinine in patients admitted to the intensive care unit [ 26 ]. Other studies have shown that urinary FABP1 levels do not increase in patients with liver dysfunction alone [ 27 ] or nephrotic syndrome with minimal glomerular abnormalities [ 28 , 29 ]. It has also been shown that an increase in urinary FABP1 levels is not associated with elevated serum FABP1 levels in patients with septic shock [ 30 ] or in those who have undergone cardiac surgery [ 31 ].…”

Infection of Human Endothelial Cells with Lassa Virus Induces Early but Transient Activation and Low Type I IFN Response Compared to the Closely-Related Nonpathogenic Mopeia Virus

“…Only a few proteins were found to be differentially secreted into the supernatants of infected cells, but striking differences were observed between the two viruses. Indeed, LASV induced the early release of MAST4, a serine/threonine kinase [ 71 ]; FABP1, a lipid chaperone [ 72 ]; and kallikrein (KLKB1). Tissue kallikrein, a serine protease, is known to be synthesized and released by human ECs, resulting in the generation of kinins, such as bradykinin [ 73 ].…”

The Role of Metabolic Dysfunction–Associated Fatty Liver Disease in Developing Chronic Kidney Disease: Longitudinal Cohort Study

“…Second, a study showed that microbiota from the intestines as well as the intestinal barrier integrity might affect the correlation between NAFLD and CKD through the gut-liver-kidney signaling axis [30]. Studies have shown that the dysregulation of adipokines in patients with MAFLD, including decreased adiponectin and increased fatty acid-binding protein 4 [31], may lead to renal dysfunction [32], glomerular injury [33], tubule-interstitial injury [34], and a decline of eGFR [35].…”