Effect of erythropoietin on urinary liver-type fatty-acid-binding protein in patients with chronic renal failure and anemia.
OBJECTIVE
The urinary liver-type fatty-acid-binding protein (L-FABP) level reflects the clinical progression of chronic kidney disease. We conducted a study to determine whether administration of erythropoietin (EPO), which is produced in response to hypoxic stress, affects urinary protein excretion and L-FABP levels in patients with chronic renal failure (CRF) and anemia.


METHODS
The study was an interventional trial that included 20 anemic CRF patients (median serum creatinine level 2.0 mg/dl, range 1.3-2.9 mg/dl; median hemoglobin concentration 9.2 g/dl, range 8.2-9.8 g/dl; median estimated glomerular filtration rate 20.5 ml/min, range 15.0-28.0 ml/min; group A). Recombinant EPO (12,000 U twice/month) was given to these patients for 6 months. Urinary protein, L-FABP, 8-hydroxy-2'-deoxyguanosine, and hemoglobin levels were measured before and 3 and 6 months after treatment. Twenty nonanemic CRF patients were enrolled as controls (group B).


RESULTS
After 6 months, the hemoglobin level was increased as compared with the baseline level in group A treated with EPO (median 11.3 g/dl, range 9.3-13.8 g/dl, vs. median 9.2 g/dl, range 8.2-9.8 g/dl; p < 0.01) but not in the untreated group B (median 11.8 g/dl, range 10.2-13.0 g/dl, vs. median 12.1 g/dl, range 10.8-13.4 g/dl; not significant). The urinary protein excretion was decreased as compared with the baseline level in group A (median 1.2 g/day, range 0.6-1.9 g/day, vs. median 1.9 g/day, range 1.1-2.6 g/day; p < 0.01) but not in group B (median 1.4 g/day, range 0.7-2.2 g/day, vs. median 1.6 g/day, range 0.7-2.3 g/day; not significant). The urinary L-FABP level was also decreased as compared with the baseline level in group A (median 50.0 microg/g creatinine, range 7.5-90.0 microg/g creatinine, vs. median 115.0 microg/g creatinine, range 20.0-225.0 microg/g creatinine; p < 0.01) but not in group B (median 82.0 microg/g creatinine, range 15.5-158.0 microg/g creatinine, vs. median 76.0 microg/g creatinine, range 25.0-138.5 microg/g creatinine; not significant). The glomerular filtration rate changed little throughout the study period in either group. The urinary 8-hydroxy-2'-deoxyguanosine level was decreased as compared with the baseline level in group A (median 22.0 ng/mg creatinine, range 8.0-30.0 ng/mg creatinine, vs. median 38.5 ng/mg creatinine, range 14.0-68.0 ng/mg creatinine; p < 0.01) but not in group B (median 33.0 ng/mg creatinine, range 9.0-56.0 ng/mg creatinine, vs. median 30.0 ng/mg creatinine, range 10.0-54.0 ng/mg creatinine; not significant).


CONCLUSIONS
EPO supplementation may ameliorate renal tubular damage, in part, due to a reduction of oxidative stress in CRF patients with anemia.
Nakamura
Tsukasa
T
Department of Internal Medicine, Shinmatsudo Central General Hospital, Chiba, Japan.
Sugaya
Takeshi
T
Kawagoe
Yasuhiro
Y
Suzuki
Tsukasa
T
Ueda
Yoshihiko
Y
Koide
Hikaru
H
D000328:Adult; D000368:Aged; D000740:Anemia / Q000209:etiology / Q000517:prevention & control* / Q000652:urine*; D004921:Erythropoietin / Q000627:therapeutic use*; D050556:Fatty Acid-Binding Proteins / Q000652:urine*; D005260:Female; D006454:Hemoglobins / Q000032:analysis*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications / Q000188:drug therapy* / Q000652:urine*; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins; D016896:Treatment Outcome
C493319:FABP1 protein, human; D050556:Fatty Acid-Binding Proteins; D006454:Hemoglobins; D011994:Recombinant Proteins; D004921:Erythropoietin