Candesartan Reduces Urinary Fatty Acid-Binding Protein Excretion in Patients with Autosomal Dominant Polycystic Kidney Disease

Abstract

Free fatty acids (FFAs) bound to albumin are overloaded in renal proximal tubules and exacerbate tubulointerstitial damage. Liver-type fatty acid-binding protein (L-FABP) is an intracellular carrier protein of FFAs that is expressed in renal proximal tubules in humans. Urinary L-FABP reflects the clinical prognosis of chronic glomerulonephritis. The aim of the present study was to determine whether urinary L-FABP excretion is altered in patients with autosomal dominant polycystic kidney disease (ADPKD) and whether candesartan cilexetil, an angiotensin II receptor antagonist, affects these levels. Subjects comprised 20 normotensive ADPKD patients (8 men and 12 women, mean age 42.6 years) and 20 age-matched healthy volunteers (8 men and 12 women, mean age 44.0 years). The 20 ADPKD patients participated in a randomized double-blind placebo-controlled study of candesartan cilexetil for 6 months. Urinary L-FABP levels were measured by a newly established ELISA method. Urinary L-FABP levels were significantly higher in ADPKD patients (154.5 +/- 110.6 microg/g Cr) than in healthy subjects (5.5 +/- 3.8 microg/g Cr) (P < 0.001). Candesartan cilexetil reduced urinary L-FABP levels from 168.5 +/- 104.5 microg/g Cr to 98.5 +/- 68.5 microg/g Cr after 3 months (P < 0.01) and to 44.6 +/- 30.8 microg/g Cr after 6 months (P < 0.001). Placebo had no effect on L-FABP levels (before, 140.5 +/- 100.5 microg/g Cr; at 3 months, 148.5 +/- 108.5 microg/g Cr; at 6 months, 150.5 +/- 110.8 microg/g Cr). During the 6 months, serum creatinine, blood urea nitrogen, 24-hour creatinine clearance and blood pressure showed little change in either group. Increased urinary L-FABP levels may be associated with the development of ADPKD, and candesartan cilexetil has a beneficial effect on reducing these levels.