Effect of Erythropoietin on Urinary Liver-Type Fatty-Acid-Binding Protein in Patients with Chronic Renal Failure and Anemia

Abstract

Background/Aim: 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 µg/g creatinine, range 7.5–90.0 µg/g creatinine, vs. median 115.0 µg/g creatinine, range 20.0–225.0 µg/g creatinine; p < 0.01) but not in group B (median 82.0 µg/g creatinine, range 15.5–158.0 µg/g creatinine, vs. median 76.0 µg/g creatinine, range 25.0–138.5 µg/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). Conclusion: EPO supplementation may ameliorate renal tubular damage, in part, due to a reduction of oxidative stress in CRF patients with anemia.

Anemia, Diabetes, and Chronic Kidney Disease

“…Recently, Nakamura et al (34) demonstrated that administration of an erythropoietin-stimulating agent to patients with anemia and CKD decreased urine fatty acid–binding protein—a molecule known to be associated with increased risk for kidney disease progression—suggesting that ESA may have a renoprotective effect independent of Hb level. However, in clinical trials, erythropoietin has not yet been proven to slow kidney disease progression in patients with diabetes and nephropathy.…”

Protective effect of erythropoietin against 1-methyl-4-phenylpyridinium-induced neurodegenaration in PC12 cells

“…Previous studies found that EPO could ameliorate the oxidative stress in several quite different disorders [4][5][6] . It has been also reported that EPO displays efficient neuroprotective properties in a spectrum of different animal models, including ischemia/hypoxia, excitotoxic paradigms, traumatic brain and spinal cord injury, and retina/optic nerve damage in inflammatory/auto-immunological diseases [7] .…”

Urinary levels of early kidney injury molecules in children with vitamin B12 deficiency

“…In chronic renal failure, urinary injury biomarkers were found to be decreased if low hemoglobin levels corrected by the administration of erythropoietin. 9 Anemia occurring in CD deficiency may lead to chronic hypoxia. Renal tubular cells had a high metabolic activity and oxygen consumption and highly susceptible to hypoxia.…”