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.

Keywords:
Chronic renal failure, Anemia, Erythropoietin, Liver-type fatty-acid-binding protein
1.
Eckardt KU: Pathophysiology of renal anemia. Clin Nephrol 2000;53(1 Suppl):S2–S8.
2.
Grune T, Sommerburg O, Siems WG: Oxidative stress in anemia. Clin Nephrol 2000;53(1 Suppl):S18–S22.
3.
Abdelrahman M, Sharples EJ, McDonald MC, Collin M, Patel NS, Yaqoob MM, Thiemermann C: Erythropoietin attenuates the tissue injury associated with hemorrhagic shock and myocardial ischemia. Shock 2004;22:63–69.
4.
Sharples EJ, Patel N, Brown P, Stewart K, Mota-Philipe H, Sheaff M, Kieswich J, Allen D, Harwood S, Raftery M, Thiemermann C, Yaqoob MM: Erythropoietin protects the kidney against the injury and dysfunction caused by ischemia-reperfusion. J Am Soc Nephrol 2004;15:2115–2124.
5.
Vesey DA, Cheung C, Pat B, Endre Z, Gobe G, Johnson DW: Erythropoietin protects against ischaemic acute renal injury. Nephrol Dial Transplant 2004;19:348–355.
6.
Kamijo A, Kimura K, Sugaya T, Yamanouchi M, Hikawa A, Hirano N, Goto A, Omata M: Urinary fatty acid-binding protein as a new clinical marker of the progression of chronic renal disease. J Lab Clin Med 2004;143:23–30.
7.
Ishimitsu T, Ohta S, Saito M, Teranishi M, Inada H, Yoshii M, Minami J, Ono H, Hikawa A, Shibata N, Sugaya K, Kamijo A, Kimura K, Ohrui M, Matsuoka H: Urinary excretion of liver fatty acid-binding protein in health-check participants. Clin Exp Nephrol 2005;9:34–39.
8.
Ayus JC, Go AS, Valderrabano F, Verde E, de Vinuesa SG, Achinger SG, Lorenzo V, Arieff AI, Luno J: Effects of erythropoietin on left ventricular hypertrophy in adults with severe chronic renal failure and hemoglobin <10 g/dl. Kidney Int 2005;68:788–795.
9.
Kamijo A, Sugaya T, Hikawa A, Okada M, Okuma F, Yamanouchi M, Honda A, Okabe M, Fujino T, Hirata Y, Omata M, Kaneko R, Fujii H, Fukamizu A, Kimura K: Urinary excretion of fatty acid binding protein reflects stress overload on the proximal tubules. Am J Pathol 2004;165:1243–1255.
10.
McClellan WM, Jurkovitz C, Abramson J: The epidemiology and control of anaemia among pre-ESRD patients with chronic kidney disease. Eur J Clin Invest 2005;35(Suppl 3):58–65.
11.
Heyman SN, Rosenberger C, Rosen S: Erythropoietin: a potential remedy for renal tubular injury? Kidney Int 2004;65:737–738.
12.
Teplan V, Schuck O, Knotek A, Hajny J, Horackova M, Kvapil M: Enhanced metabolic effect of erythropoietin and keto acids in CRF patients on low-protein diet: Czech multicenter study. Am J Kidney Dis 2003;41(Suppl 1):S26–S30.
13.
Lee SH, Li C, Lim SW, Ahn KO, Choi BS, Kim YS, Moon IS, Kim J, Bang BK, Yang CW: Attenuation of interstitial inflammation and fibrosis by recombinant human erythropoietin in chronic cyclosporine nephropathy. Am J Nephrol 2005;25:64–76.
14.
Rossert J, Fouqueray B, Boffa JJ: Anemia management and the delay of chronic renal failure progression. J Am Soc Nephrol 2003;14(7 Suppl 2):S173–S177.
15.
Gouva C, Nikolopoulos P, Ioannidis JP, Siamopoulos KC: Treating anemia early in renal failure patients slows the decline of renal function: a randomized controlled trial. Kidney Int 2004;66:753–760.
16.
Matthys E, Patel Y, Kreisberg J, Stewart JH, Venkatachalam M: Lipid alterations induced by renal ischemia: pathogenic factor in membrane damage. Kidney Int 1984;26:153–161.
17.
Kanauchi M, Nishioka H, Hashimoto T: Oxidative DNA damage and tubulointerstitial injury in diabetic nephropathy. Nephron 2002;91:327–329.
18.
Stoll LL, McCormick ML, Denning GM, Weintraub NL: Antioxidant effects of statins. Drugs Today (Barc) 2004;40:975–990.
19.
Manotham K, Tanaka T, Matsumoto M, Ohse T, Miyata T, Inagi R, Kurokawa K, Fujita T, Nangaku M: Evidence of tubular hypoxia in the early phase in the remnant kidney model. J Am Soc Nephrol 2004;15:1277–1288.
20.
Fliser D, Wagner KK, Loos A, Tsikas D, Haller H: Chronic angiotensin II receptor blockade reduces (intra)renal vascular resistance in patients with type 2 diabetes. J Am Soc Nephrol 2005;16:1135–1140.
21.
Kamijo A, Sugaya T, Hikawa A, Yamanouchi M, Hirata Y, Ishimitsu T, Numabe A, Takagi M, Hayakawa H, Tabei F, Sugimoto T, Mise N, Omata M, Kimura K: Urinary liver-type fatty acid binding protein as a useful biomarker in chronic kidney disease. Mol Cell Biochem 2006;284:175–182.
© 2006 S. Karger AG, Basel
2006
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.