Beneficial effects of olmesartan and temocapril on urinary liver-type fatty acid-binding protein levels in normotensive patients with immunoglobin A nephropathy.
BACKGROUND
Liver-type fatty acid-binding protein (L-FABP) is a clinical biomarker of tubulointerstitial damage, which plays an essential role in the progression of chronic kidney disease (CKD), including immunoglobin A (IgA) nephropathy. The effect of combination therapy with the angiotensin receptor blocker (ARB) and the angiotensin-converting enzyme inhibitor (ACEI) on CKD has not been elucidated.


METHODS
Twenty-four normotensive patients with IgA nephropathy were randomly assigned to receive olmesartan 10 mg/day, temocapril 2 mg/day, or combination therapy with both drugs. Urinary levels of L-FABP as well as 8-hydroxydeoxyguanosine (8-OHdG) and protein excretion were measured before and after 3 months of treatment. The chronicity index and activity index were also assessed by histopathologic findings.


RESULTS
Urinary levels of L-FABP and 8-OHdG were higher in patients with IgA nephropathy than in age-matched and sex-matched healthy controls (122.5 +/- 25.5 v 6.4 +/- 3.8 mug/g.creatinine, P < .001; and 22.6 +/- 4.4 v 4.8 +/- 1.4 ng/mg.creatinine, P < .01, respectively). Urinary levels of L-FABP were correlated with those of 8-OHdG (baseline, P = .0001; after 3 months, P = .008) and the severity of proteinuria (baseline, P = .0015; after 3 months, P = .0001). The percent reductions in urinary levels of L-FABP and 8-OHdG, protein excretion, and activity index after 3 months were greater in the combination therapy group, compared with each monotherapy group of olmesartan (P < .05) and temocapril (P < .05).


CONCLUSIONS
The data suggest that a combination therapy of ARB plus ACEI has a greater beneficial effect on renal injury compared with monotherapy using ARB or ACEI in normotensive patients with IgA nephropathy.
Nakamura
Tsukasa
T
Department of Medicine, Shinmatsudo Central General Hospital, Matsudo, Japan.
Inoue
Teruo
T
Sugaya
Takeshi
T
Kawagoe
Yasuhiro
Y
Suzuki
Tsukasa
T
Ueda
Yoshihiko
Y
Koide
Hikaru
H
Node
Koichi
K
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000328:Adult; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D001794:Blood Pressure / Q000502:physiology; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000652:urine; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D050556:Fatty Acid-Binding Proteins / Q000652:urine*; D005260:Female; D005922:Glomerulonephritis, IGA / Q000188:drug therapy* / Q000503:physiopathology / Q000652:urine*; D006339:Heart Rate / Q000502:physiology; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D008297:Male; D011507:Proteinuria / Q000517:prevention & control; D013777:Tetrazoles / Q000627:therapeutic use*; D013841:Thiazepines / Q000627:therapeutic use*
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D050556:Fatty Acid-Binding Proteins; D007093:Imidazoles; D013777:Tetrazoles; D013841:Thiazepines; D000080242:8-Hydroxy-2'-Deoxyguanosine; C055603:temocapril hydrochloride; C437965:olmesartan; D003849:Deoxyguanosine