Nephrotoxicity pp 285-290 | Cite as

The Effects of Cyclosporin a on the Urine Excretion of Specific Proteins in Humans

  • Anne Dawnay
  • Michael Lucey
  • Carolyn Thornley
  • Robert Beetham
  • Bill Cattell
  • Roger Williams
Chapter

Abstract

Cyclosporin A (CyA) is widely used as an immunosuppressant following organ transplantation and in the treatment of various autoimmune disorders. A major disadvantage is its nephrotoxicity which is probably of multifactorial origin, involving acute, reversible haemodynamic changes and irreversible tubulointerstitial injury and focal glomerulosclerosis (Cohen et al, 1984; Klintmalm et al, 1984; Myers et al, 1984; Palestine et al, 1986). There is no satisfactory animal model for CyA nephrotoxicity and its assessment in CyA treated renal transplant recipients is complicated by the coexistence of other renal disorders. For these reasons, we have chosen to study a group of patients being treated with long-term CyA for an autoimmune disorder, primary biliary cirrhosis (PBC).

Keywords

Primary Biliary Cirrhosis Retinol Binding Protein Tubular Proteinuria Serum Retinol Binding Protein Focal Glomerulosclerosis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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References

  1. Avis, P. J. G., Williams, J. D., Salaman, J. R., Asscher, A. W., and Newcombe, R., 1985, Tamm-Horsfall protein concentration in cyclosporin treated renal transplant recipients, Lancet, 1: 154.CrossRefGoogle Scholar
  2. Beetham, R., Dawnay, A., Landon, J., and Cattell, W., 1985, A radioimmunoassay for retinol binding protein in serum and urine, Clin. Chem., 31: 1364.PubMedGoogle Scholar
  3. Bennett, W., and Pulliam, J., 1983, Cyclosporine nephrotoxicity, Ann. Intern. Med., 99: 851.PubMedCrossRefGoogle Scholar
  4. Beorchia, S., Vincent, C., Revillard, J., and Trepo, C., 1981, Elevation of serum beta-2-microglobulin in liver diseases, Clin. Chim. Acta, 109: 245.PubMedCrossRefGoogle Scholar
  5. Bernard, AF Moreau, D., and Lauwerys, R., 1982, Comparison of retinol binding protein and beta-2-microglobulin determination in urine for the early detection of tubular proteinuria, Clin. Chim. Acta, 126: 1.PubMedCrossRefGoogle Scholar
  6. Cohen, D., Loertscher, R., Rubin, M., Tilney, N., Carpenter, C., and Strom, T., 1984, Cyclosporine: a new immunosuppressive agent for organ transplantation, Ann. Intern. Med., 101: 667.PubMedCrossRefGoogle Scholar
  7. Dawnay, A., McLean, C., and Cattell, W., 1980, The development of a radioimmunoassay for Tamm-Horsfall glycoprotein in serum, Biochem. J., 185: 679.PubMedGoogle Scholar
  8. Dawnay, A., Thornley, C., and Cattell, W., 1982, An improved radioimmunoassay for urinary Tamm-Horsfall glycoprotein, Biochem. J., 206: 461.PubMedGoogle Scholar
  9. Gnutzmann, K., Hering, K., and Gutsche, H-U., 1986, Effect of cyclosporine on the diluting capacity of the rat kidney, Clin. Nephrol., 25(S1): S51.Google Scholar
  10. Hession, C., Decker, J., Sherblom, A., Kumar, S., Yue, C., Mattaliano, R., Tizard, R., Kawashima, E., Schmeissner, U., Heletky, S., Chow, E., Burne, C., Shaw, A., and Muchmore, A 1987, Uromodulin (Tamm-Horsfall glycoprotein): A renal ligand for lymphokines, Science, 237: 1479.PubMedCrossRefGoogle Scholar
  11. Izumi, N., Hasumura, Y., and Takeuchi, J., 1983, Hypouricaemia and hyperuricosuria as expressions of renal tubular damage in primary biliary cirrhosis, Hepatology, 3: 719.PubMedCrossRefGoogle Scholar
  12. Klintmalm, G., Bohman, S., Sundelin, B., and Wilczek, H., 1984, Interstitial fibrosis in renal allografts after 12 to 46 months of cyclosporin treatment, Lancet, 2: 950.PubMedCrossRefGoogle Scholar
  13. McFarlane, I., Tsantoulas, D., Cochrane, A., Eddleston, A., and Williams, R., 1979, Renal tubular acidosis and Tamm-Horsfall glycoprotein, In: “Immune Reactions in Liver Disease”, A. Addleston, ed., Pitman, London.Google Scholar
  14. Muller-Suur, R., and Davis, S., 1986, Effect of cyclosporine A on renal electrolyte transport, Clin. Nephrol., 25(S1): S57.Google Scholar
  15. Myers, B., Ross, J., Newton, L., Luetscher, J., and Perlroth, M., 1984, Cyclosporine associated chronic nephropathy, New Engl. J. Med., 311: 699.PubMedCrossRefGoogle Scholar
  16. Nyberg, A., Loof, L., and Hallgren, R., 1985, Serum beta-2-microglobulin levels in primary biliary cirrhosis, Hepatologv, 5: 282.CrossRefGoogle Scholar
  17. Palestine, A., Austin, H., Balow, J., Antonovych, T., Sabnis, S., Preuss, H., and Nussenblatt, R., 1986, Renal histopathologic alterations in patients treated with cyclosporine for uveitis, New Engl. J. Med., 314: 1293.PubMedCrossRefGoogle Scholar
  18. Rask, L., Anundi, H., and Bohme, J., 1980, The retinol binding protein, Scand. J. Clin. Lab. Invest., 40 (S154): 45.Google Scholar
  19. Siegel, S., 1956, “Non-parametric Statistics for the Behavioural Sciences”, McGraw-Hill Kogakusha, Tokyo.Google Scholar
  20. Sikri, K., Foster, C., MacHugh, N., and Marshall, R., 1981, Localisation of Tamm-Horsfall glycoprotein in the human kidney using immunofluorescence and immunoelectronmicroscopical techniques, J. Anat., 132: 597.PubMedGoogle Scholar
  21. Silver, A., Dawnay, A., Landon, J., and Cattell, W., 1986, Immunoassays for low concentrations of albumin in urine, Clin. Chem., 32: 1303.PubMedGoogle Scholar
  22. Thiel, G., 1986, Experimental cyclosporine a nephrotoxicity: A summary of the International Workshop, Clin. Nephrol., 25(S1): S205.Google Scholar
  23. Thiru, S., Maher, E., Hamilton, D., Evans, D., and Calne, R., 1983, Tubular changes in renal transplant recipients on cyclosporine, Transplant. Proc., 15(S1): 2846.Google Scholar
  24. Thornley, C., Dawnay, A., and Cattell, W., 1985, Human Tamm-Horsfall glycoprotein: urinary and plasma levels in normal subjects and patients with renal disease determined by a fully validated radioimmunoassay, Clin. Sci., 68: 529.PubMedGoogle Scholar
  25. Tucker, S., Boyd, P., Thompson, A., and Price, R., 1975, Automated assay of N-acetyl-beta-glucosaminidase in normal and pathological human urine, Clin. Chim. Acta, 62: 333.PubMedCrossRefGoogle Scholar
  26. Wenger, R., 1986, Cyclosporine, In: “Progress in Clincal Biochemistry and Medicine”, W. Berger, ed., Springer-Verlag, Berlin.Google Scholar
  27. Whiting, P., Thomson, A., and Simpson, J., 1986, Cyclosporine and renal enzyme excretion, Clin. Nephrol., 25(51): 5100.Google Scholar

Copyright information

© Springer Science+Business Media New York 1989

Authors and Affiliations

  • Anne Dawnay
    • 1
    • 2
  • Michael Lucey
    • 1
    • 2
  • Carolyn Thornley
    • 1
    • 2
  • Robert Beetham
    • 1
    • 2
  • Bill Cattell
    • 1
    • 2
  • Roger Williams
    • 1
    • 2
  1. 1.Departments of Chemical Pathology and Nephrology, St Bartholomew’s Centre for ResearchSt Bartholomew’s HospitalLondonUK
  2. 2.The Liver UnitKing’s College HospitalLondonUK

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