Urinary excretion of fatty acid-binding proteins in idiopathic membranous nephropathy

Abstract

It is suggested that proteinuria contributes to progressive renal failure by inducing tubular cell injury. The site of injury is unknown. Most studies have used markers of proximal tubular cell damage. Fatty acid-binding proteins (FABPs) are intracellular carrier proteins with different expression in the kidney. Liver-type FABP (L-FABP) is found in the cytoplasm of proximal tubules, whereas heart-type FABP (H-FABP) is localized in the distal tubules. We evaluated the urinary excretion of L-FABP and H-FABP in patients with idiopathic membranous nephropathy (iMN). We have studied 40 patients (27 males, 13 females) with iMN. The mean age was 48 +/- 15 years, serum creatinine concentration 89 +/- 17 micromol/l and proteinuria 8.9 +/- 5.0 g/24 h. Urinary L-FABP and H-FABP were measured by ELISA. Renal failure was defined as an increase in serum creatinine >25% from baseline with a serum creatinine >135 micromol/l or an increase >50% from baseline. Urinary L-FABP excretion was detectable in all but one patient. The median (range) level was 3.29 (0.7-165.6) microg/mmol creatinine (normal <0.38 microg/mmol Cr). Urinary H-FABP was undetectable in nine patients. Median level was 1.53 (0.1-90.5) microg/mmol Cr (normal <0.1 microg/mmol Cr). Both L- and H-FABP correlated with urinary beta2-microglobulin, urinary alpha1-microglobulin and IgG. Urinary H-FABP paralleled L-FABP. After a mean follow-up of 75 +/- 32 months, 16 (40%) patients have reached the predefined end point of renal failure. Both urinary L-FABP and H-FABP predicted renal outcome, with the calculated sensitivity and specificity of 81 and 83% for both. Urinary L-FABP and urinary H-FABP are increased in patients with iMN. There was a high correlation between L-FABP and H-FABP, suggesting the concurrent development or existence of proximal and distal tubular cell injury. Both L-FABP and H-FABP predicted prognosis in patients with iMN. These markers may be of interest as research tools; however, they are not superior to more conventional marker proteins.