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. 1993 Jan;91(1):251–256. doi: 10.1172/JCI116178

Increased plasma viscosity as a reason for inappropriate erythropoietin formation.

A Singh 1, K U Eckardt 1, A Zimmermann 1, K H Götz 1, M Hamann 1, P J Ratcliffe 1, A Kurtz 1, W H Reinhart 1
PMCID: PMC330021  PMID: 8423222

Abstract

The aim of this study was to examine whether altered plasma viscosity could contribute to the inappropriately low production rate of erythropoietin (EPO) observed in patients suffering from hypergammaglobulinemias associated with multiple myeloma or Waldenström's disease. We found that the EPO formation in response to anemia in these patients was inversely related to plasma viscosity. A similar inverse relationship between plasma viscosity and EPO production was seen in rats in which EPO formation had been stimulated by exchange transfusion and the plasma viscosity of which was thereby altered by using exchange solutions of different composition to alter plasma viscosity and thus whole blood viscosity independently from hematocrit. Raising the gammaglobulin concentration to approximately 40 mg/ml plasma in the rats almost totally blunted the rise in serum EPO levels despite a fall of the hematocrit to 20%. Determination of renal EPO mRNA levels by RNase protection revealed that the reductions in serum EPO levels at higher plasma viscosities were paralleled by reductions in renal EPO mRNA levels. Taken together, our findings suggest that plasma viscosity may be a significant inhibitory modulator of anemia-induced EPO formation. The increased plasma viscosity in patients with hypergammaglobulinemias may therefore contribute to the inappropriate EPO production, which is a major reason for the anemia developing in these patients.

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Selected References

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  1. Ando J., Komatsuda T., Ishikawa C., Kamiya A. Fluid shear stress enhanced DNA synthesis in cultured endothelial cells during repair of mechanical denudation. Biorheology. 1990;27(5):675–684. doi: 10.3233/bir-1990-27505. [DOI] [PubMed] [Google Scholar]
  2. Baer A. N., Dessypris E. N., Goldwasser E., Krantz S. B. Blunted erythropoietin response to anaemia in rheumatoid arthritis. Br J Haematol. 1987 Aug;66(4):559–564. doi: 10.1111/j.1365-2141.1987.tb01344.x. [DOI] [PubMed] [Google Scholar]
  3. DeForrest J. M., Hollis T. M. Shear stress and aortic histamine synthesis. Am J Physiol. 1978 Jun;234(6):H701–H705. doi: 10.1152/ajpheart.1978.234.6.H701. [DOI] [PubMed] [Google Scholar]
  4. Durie B. G., Salmon S. E. The current status and future prospects of treatment for multiple myeloma. Clin Haematol. 1982 Feb;11(1):181–210. [PubMed] [Google Scholar]
  5. Eckardt K. U., Hartmann W., Vetter U., Pohlandt F., Burghardt R., Kurtz A. Serum immunoreactive erythropoietin of children in health and disease. Eur J Pediatr. 1990 Apr;149(7):459–464. doi: 10.1007/BF01959395. [DOI] [PubMed] [Google Scholar]
  6. Eckardt K. U., Kurtz A., Hirth P., Scigalla P., Wieczorek L., Bauer C. Evaluation of the stability of human erythropoietin in samples for radioimmunoassay. Klin Wochenschr. 1988 Mar 15;66(6):241–245. doi: 10.1007/BF01748163. [DOI] [PubMed] [Google Scholar]
  7. Erslev A. J., Wilson J., Caro J. Erythropoietin titers in anemic, nonuremic patients. J Lab Clin Med. 1987 Apr;109(4):429–433. [PubMed] [Google Scholar]
  8. Frangos J. A., Eskin S. G., McIntire L. V., Ives C. L. Flow effects on prostacyclin production by cultured human endothelial cells. Science. 1985 Mar 22;227(4693):1477–1479. doi: 10.1126/science.3883488. [DOI] [PubMed] [Google Scholar]
  9. Grabowski E. F., Jaffe E. A., Weksler B. B. Prostacyclin production by cultured endothelial cell monolayers exposed to step increases in shear stress. J Lab Clin Med. 1985 Jan;105(1):36–43. [PubMed] [Google Scholar]
  10. Hochberg M. C., Arnold C. M., Hogans B. B., Spivak J. L. Serum immunoreactive erythropoietin in rheumatoid arthritis: impaired response to anemia. Arthritis Rheum. 1988 Oct;31(10):1318–1321. doi: 10.1002/art.1780311016. [DOI] [PubMed] [Google Scholar]
  11. Jelkmann W. Renal erythropoietin: properties and production. Rev Physiol Biochem Pharmacol. 1986;104:139–215. doi: 10.1007/BFb0031014. [DOI] [PubMed] [Google Scholar]
  12. Koury S. T., Bondurant M. C., Koury M. J. Localization of erythropoietin synthesizing cells in murine kidneys by in situ hybridization. Blood. 1988 Feb;71(2):524–527. [PubMed] [Google Scholar]
  13. Lacombe C., Da Silva J. L., Bruneval P., Fournier J. G., Wendling F., Casadevall N., Camilleri J. P., Bariety J., Varet B., Tambourin P. Peritubular cells are the site of erythropoietin synthesis in the murine hypoxic kidney. J Clin Invest. 1988 Feb;81(2):620–623. doi: 10.1172/JCI113363. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Ludwig H., Fritz E., Kotzmann H., Höcker P., Gisslinger H., Barnas U. Erythropoietin treatment of anemia associated with multiple myeloma. N Engl J Med. 1990 Jun 14;322(24):1693–1699. doi: 10.1056/NEJM199006143222402. [DOI] [PubMed] [Google Scholar]
  15. Radtke H. W., Claussner A., Erbes P. M., Scheuermann E. H., Schoeppe W., Koch K. M. Serum erythropoietin concentration in chronic renal failure: relationship to degree of anemia and excretory renal function. Blood. 1979 Oct;54(4):877–884. [PubMed] [Google Scholar]
  16. Ratcliffe P. J., Jones R. W., Phillips R. E., Nicholls L. G., Bell J. I. Oxygen-dependent modulation of erythropoietin mRNA levels in isolated rat kidneys studied by RNase protection. J Exp Med. 1990 Aug 1;172(2):657–660. doi: 10.1084/jem.172.2.657. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Rege A. B., Brookins J., Fisher J. W. A radioimmunoassay for erythropoietin: serum levels in normal human subjects and patients with hemopoietic disorders. J Lab Clin Med. 1982 Dec;100(6):829–843. [PubMed] [Google Scholar]
  18. Rubanyi G. M., Freay A. D., Kauser K., Johns A., Harder D. R. Mechanoreception by the endothelium: mediators and mechanisms of pressure- and flow-induced vascular responses. Blood Vessels. 1990;27(2-5):246–257. doi: 10.1159/000158816. [DOI] [PubMed] [Google Scholar]
  19. Sherwood J. B., Goldwasser E., Chilcote R., Carmichael L. D., Nagel R. L. Sickle cell anemia patients have low erythropoietin levels for their degree of anemia. Blood. 1986 Jan;67(1):46–49. [PubMed] [Google Scholar]
  20. Taylor J., Mactier R. A., Stewart W. K., Henderson I. S. Effect of erythropoietin on anaemia in patients with myeloma receiving haemodialysis. BMJ. 1990 Sep 8;301(6750):476–477. doi: 10.1136/bmj.301.6750.476. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Yoshizumi M., Kurihara H., Sugiyama T., Takaku F., Yanagisawa M., Masaki T., Yazaki Y. Hemodynamic shear stress stimulates endothelin production by cultured endothelial cells. Biochem Biophys Res Commun. 1989 Jun 15;161(2):859–864. doi: 10.1016/0006-291x(89)92679-x. [DOI] [PubMed] [Google Scholar]

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