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 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.


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.
Nakamura
Tsukasa
T
Department of Medicine, Shinmatsudo Central General Hospital, Chiba, Japan.
Sugaya
Takeshi
T
Kawagoe
Yasuhiro
Y
Ueda
Yoshihiko
Y
Osada
Shiwori
S
Koide
Hikaru
H
D000328:Adult; D000368:Aged; D001562:Benzimidazoles / Q000627:therapeutic use*; D001713:Biphenyl Compounds / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016891:Polycystic Kidney, Autosomal Dominant / Q000188:drug therapy* / Q000235:genetics / Q000652:urine*; D013777:Tetrazoles / Q000627:therapeutic use*
D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; C077793:candesartan cilexetil