Candesartan reduces urinary fatty acid-binding protein excretion in patients with autosomal dominant polycystic kidney disease

Background. 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. Methods: 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. Results: Urinary L-FABP levels were significantly higher in ADPKD patients (154.5 +/- 110.6 mu g/g Cr) than in healthy subjects (5.5 +/- 3.8 mu g/g Cr) (P < 0.001). Candesartan cilexetil reduced urinary L-FABP levels from 168.5 +/- 104.5 mu g/g Cr to 98.5 +/- 68.5 mu g/g Cr after 3 months (P < 0.01) and to 44.6 +/- 30.8 mu g/g Cr after 6 months (P < 0.001). Placebo had no effect on L-FABP levels (before, 140.5 +/- 100.5 mu g/g Cr; at 3 months, 148.5 +/- 108.5 mu g/g Cr; at 6 months, 150.5 +/- 110.8 mu g/g Cr). During the 6 months, serum creatinine, blood urea nitrogen, 24-hour creatinine clearance and blood pressure showed little change in either group. Conclusions: Increased urinary L-FABP levels may be associated with the development of ADPKD, and candesartan cilexetil has a beneficial effect on reducing these levels.