Urinary excretion of fatty acid-binding protein reflects stress overload on the proximal tubules

Am J Pathol. 2004 Oct;165(4):1243-55. doi: 10.1016/S0002-9440(10)63384-6.

Abstract

Urinary excretion of human liver-type fatty acid-binding protein (hL-FABP), which is expressed in human proximal tubules and engaged in free fatty acid (FFA) metabolism, was reported to reflect the clinical prognosis of chronic kidney disease. Here we have investigated the pathophysiological significance of hL-FABP in a model of protein overload nephropathy. Because L-FABP is not expressed in the wild-type mice, we generated hL-FABP chromosomal gene transgenic (Tg) mice. Tg mice were intraperitoneally injected with bovine serum albumin (BSA) replete with FFAs (r-BSA group) or FFA-depleted BSA (d-BSA group). The r-BSA group developed significantly more severe tubulointerstitial damage than did the d-BSA group. Renal expression of the hL-FABP gene was more up-regulated, and urinary excretion of hL-FABP was significantly higher, in the r-BSA group than in the d-BSA group. Furthermore, compared with their wild-type littermates injected with r-BSA, the number of infiltrated macrophages was significantly attenuated in Tg mice injected with it on day 28. In patients with kidney disease (n = 50), urinary hL-FABP was correlated with both urinary protein and the severity of tubulointerstitial injury. In conclusion, our experimental model suggests that urinary excretion of hL-FABP reflects stresses, such as urinary protein overload, on the proximal tubules. The clinical observations support this hypothesis.

MeSH terms

  • Animals
  • Blotting, Northern
  • Blotting, Western
  • Carrier Proteins / genetics
  • Carrier Proteins / urine*
  • Disease Models, Animal
  • Enzyme-Linked Immunosorbent Assay
  • Fatty Acid-Binding Proteins
  • Female
  • Gene Expression Regulation
  • Humans
  • Immunohistochemistry
  • Kidney Diseases / metabolism*
  • Kidney Diseases / pathology*
  • Kidney Tubules, Proximal / metabolism*
  • Kidney Tubules, Proximal / pathology*
  • Male
  • Mice
  • Mice, Transgenic
  • Middle Aged
  • Proteinuria / metabolism
  • Serum Albumin, Bovine / analysis

Substances

  • Carrier Proteins
  • FABP1 protein, human
  • Fabp1 protein, mouse
  • Fatty Acid-Binding Proteins
  • Serum Albumin, Bovine