Journal Mobile Options
Table of Contents
Vol. 10, No. 5-6, 2002
Issue release date: 2002

Unexpected Renal Actions of Erythropoietin

Westenfelder C.
To view the fulltext, log in and/or choose pay-per-view option

Individual Users: Register with Karger Login Information

Please create your User ID & Password

Contact Information

I have read the Karger Terms and Conditions and agree.

To view the fulltext, please log in

To view the pdf, please log in


Erythropoietin (EPO) in the renal cortex is synthesized by fibroblast-like cells that are in direct contact with capillaries and adjacent tubular cells. Prompted by this anatomical relationship, we asked whether renal cells express EPO receptors (EPORs) through which EPO could act as a renotropic cytokine. We found that all regions of human, rat and mouse kidney, mesangial and proximal and distal tubular cells express authentic EPORs. Similar EPOR expression was detected in kidney cancer cells, and in cyst epithelia from polycystic kidneys. In vitro, EPO stimulated mitogenesis in all normal and malignant cells, and cell survival and motogenesis in injured tubular cells. Since the normal kidney is essentially unresponsive to EPO, we hypothesized that EPO’s cytokine effects in the kidney are revealed when tubular cells are induced to proliferate by a prior insult, as occurs in acute renal failure. Accordingly, we found that EPO treatment of rats with ‘ischemic’ acute renal failure afforded renoprotection and accelerated functional recovery.

Copyright / Drug Dosage

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 or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
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 goverment 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.


  1. Jelkmann W: Erythropoietin: Structure, control of production and function. Physiol Rev 1992;72:449–489.
  2. Maxwell PH, Osmond MK, Pugh CW, Heryet A, Nicholls LG, Tan CC, Doe BG, Ferguson DJ, Johnson MH, Ratcliffe PJ: Identification of the renal erythropoietin-producing cells using transgenic mice. Kidney Int 1993;44:1149–1162.
  3. Heidenreich S, Rahn KH, Zidek W: Direct vasopressor effect of recombinant human erythropoietin on renal resistance vessels. Kidney Int 1991;39:259–265.
  4. Nushiro N, Sakamaki T, Hoshino J, Nakamura T, Sakamoto H, Imai Y, Seino M, Omata K, Sekino H, Abe K: Recombinant human erythropoietin stimulates tubular reabsorption of sodium in anesthetized rabbits. Hypertens Res 1995;18:203–207.
  5. Allon M: Renal abnormalities in sickle cell disease. Arch Intern Med 1990;150:501–504.
  6. Kaissling B, Spiess S, Rinne B, Le Hir M: Effects of anemia on morphology of rat renal cortex. Am J Physiol 1993;264:F608–F617.

    External Resources

  7. Spivak JL, Watson AJ: Hematopoiesis and the kidney; in Seldin DW, Giebisch G (eds): The Kidney: Physiology and Pathology. New York, Raven Press, 1992 pp 1553–1593.
  8. Youssoufian H, Longmore G, Neumann D, Yoshimura A, Lodish HF: Structure, function and activation of the erythropoietin receptor. Blood 1993;81:2223–2236.
  9. Anagnostou A, Lee ES, Kessimian N, Levinson R, Steiner M: Erythropoietin has a mitogenic and positive chemotactic effect on endothelial cells. Proc Natl Acad Sci USA 1990;87:5978–5982.
  10. Masuda S, Nagao M, Takahata K, Konishi Y, Gallyas FJ, Tabira T, Sasaki R: Functional erythropoietin receptor of the cells with neural characteristics. Comparison with receptor properties of erythroid cells. J Biol Chem 1993;268:11208–11216.
  11. Carlini R, Reyes A, Rothstein M: Recombinant human erythropoietin stimulates angiogenesis in vitro. Kidney Int 1995;47:740–745.
  12. Sasaki R, Masuda S, Nagao M: Pleiotropic functions and tissue-specific expression of erythropoietin. News Physiol Sci 2001;16:110–113.

    External Resources

  13. Damen JE, Krystal G: Early events in erythropoietin-induced signaling. Exp Hematol 1996;24:1455–1459.
  14. Westenfelder C, Biddle DL, Baranowski RL: Human, rat and mouse kidney cells express functional erythropoietin receptors. Kidney Int 1999;55:808–820.
  15. Marrero MB, Venema RC, Ma H, Ling BN, Eaton DC: Erythropoietin receptor-operated Ca2+ channels: Activation by phospholipase Cγ1. Kidney Int 1998;53:1259–1268.
  16. Westenfelder C, Sullivan C, Baranowski RL: Mitogenic signaling of erythropoietin in murine renal proximal tubular cells involves STAT5 and c-myc. J Am Soc Nephrol 1998;9:408A.
  17. Bacallao R, Fine LG: Molecular events in the organization of renal tubular epithelium: From nephrogenesis to regeneration. Am J Physiol 1989;257:F913–F924.
  18. Toback F: Regeneration after acute tubular necrosis. Kidney Int 1992;41:226–246.
  19. Westenfelder C, Baranowski RL: Erythropoietin stimulates proliferation of human renal carcinoma cells. Kidney Int 2000;58:647–657.
  20. Westenfelder C, Baranowski RL: Erythropoietin exerts an anti-apoptotic effect in normal human proximal tubular cells but not in kidney cancer cells (‘786-0’) that lack the von Hippel-Lindau tumor suppressor gene. J Am Soc Nephrol 2001;12:623A.
  21. Rubins J: Metastatic renal cell carcinoma: Response to treatment with human recombinant erythropoietin. Ann Intern Med 1995;122:676–677.
  22. Ljungberg B, Rasmuson T, Grankvist K: Erythropoietin in renal cell carcinoma: Evaluation of its usefulness as a tumor marker. Eur Urol 1992;21:160–163.
  23. Fick GM, Gabow PA: Hereditary and acquired cystic disease of the kidney. Kidney Int 1994;46:951–964.
  24. Eckardt KU, Mollmann M, Neumann R, Brunkhorst R, Burger HU, Lonnemann G, Scholz H, Keusch G, Buchholz B, Frei U, Bauer C, Kurtz A: Erythropoietin in polycystic kidneys. J Clin Invest 1989;84:1160–1166.
  25. Franek E, Kokot F, Wiecek A, Pawlowski W, Myrta J, Szewczyk W, Bar A: Erythropoietin concentration in cyst fluid in patients with simple renal cysts. Nephron 1994;67:431–435.
  26. Westenfelder C, Baranowski RL, Soto C, Loghman-Adham M: Immortalized (SV40), cyst-derived epithelial cells in autosomal dominant polycystic kidney disease (ADPKD) retain erythropoietin receptor expression: A suitable model for the study of EPO’s potential role in cystogenesis. J Am Soc Nephrol 2000;11:400A.
  27. Nielsen O, Thaysen J: Erythropoietin deficiency in acute tubular necrosis. J Intern Med 1990;227:373–380.
  28. Wood P, Hrushesky W: Cisplatin-associated anemia: An erythropoietin deficiency syndrome. J Clin Invest 1995;95:1650–1659.

    External Resources

  29. Tan CC, Tan LH, Eckardt KU: Erythropoietin production in rats with post-ischemic acute renal failure. Kidney Int 1996;50:1958–1964.
  30. Westenfelder C, Baranowski RL, Toback FG: Mitogenic and motogenic actions of erythropoietin on tubular cells appear to accelerate functional recovery from ischemic acute renal failure in rats. J Am Soc Nephrol 2000;11:597A.
  31. Juul SE, Yachnis AT, Christensen RD: Tissue distribution of erythropoietin and erythropoietin receptor in the developing human fetus. Early Hum Dev 1998;52:235–249.
  32. Westenfelder C, Baranowski RL: Erythropoietin treatment ameliorates ischemic acute renal failure in rats by its anti-apoptotic, motogenic and mitogenic actions. J Am Soc Nephrol 2001;11:793A.
  33. Nemoto T, Yokota N, Keane WF, Rabb H: Recombinant erythropoietin rapidly treats anemia in ischemic acute renal failure. Kidney Int 2001;59:246–251.

    External Resources

  34. Vaziri N, Zhou X, Liao S: Erythropoietin enhances recovery from cisplatin-induced acute renal failure. Am J Physiol 1994;266:F360–F366.

    External Resources

  35. Star RA: Treatment of acute renal failure. Kidney Int 1998;54:1817–1831.

Pay-per-View Options
Direct payment This item at the regular price: USD 38.00
Payment from account With a Karger Pay-per-View account (down payment USD 150) you profit from a special rate for this and other single items.
This item at the discounted price: USD 26.50