European Journal of Clinical Pharmacology

, Volume 23, Issue 2, pp 161–166 | Cite as

Gentamicin and sisomicin — Induced renal tubular damage

  • G. Nicot
  • L. Merle
  • J. -P. Valette
  • J. -P. Charmes
  • G. Lachâtre


Early signs of aminoglycoside — induced renal tubular damage were detected in 26 patients given gentamicin and 23 given sisomicin. The urinary elimination of 3 low molecular weight proteins (LMWP) — beta 2 microglobulin, retinol binding protein and lysozyme (LZM), and the urinary activity of 2 enzymes — alanine aminopeptidase and N-acetylbeta-glucosaminidase — was measured before, during and after treatment. In gentamicin — treated patients LMWP elimination increased, especially LZM which rose markedly during treatment and returned to normal values after its end. Enzyme activities also rose while gentamicin was being given. Sisomicin produced smaller changes. As neither the mean serum creatinine nor the mean urinary elimination of transferrin were increased, glomerular function was probably not affected. However, tubular damage was detected, as shown by the LMWP output (especially LZM) and increased enzyme activity. Urinary LMWP and enzyme measurements are presented as sensitive and reliable methods to monitor early aminoglycoside — induced tubular impairment. It is suggested that the different renal toxicities of gentamicin and sisomicin are related to differences in their accumulation in the renal cortex.

Key words

gentamicin sisomicin nephrotoxicity aminoglycosides low molecular weight proteinuria enzymuria renal tubular damage 


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  1. 1.
    Balazs T, Roepke RR (1966) Lysozymuria induced in rats by nephrotoxic agents. Proc Soc Exp Biol Med 123: 380–385Google Scholar
  2. 2.
    Bartels H, Bohmer M, Heierli C (1972) Serum Kreatininbestimmung ohne enteiweissen. Clin Chim Acta 37: 193–197Google Scholar
  3. 3.
    Bennet WM, Plamp CE, Gilbert DN, Porter GA (1978) Kinetics of gentamicin uptake in rat cortical slices and the effect of aminoglycoside pre treatment on the transport of para-aminohippurate (PAH) and N-methyl-nicotinamide (NMN). In: Fillastre JP (ed) Nephrotoxicity. Masson, Paris New York, pp 143–156Google Scholar
  4. 4.
    Fabre J (1980) La néphrotoxicité des aminoglycosides. Néphrologie 1: 37–43Google Scholar
  5. 5.
    Houghton DC, Hartnett M, Campbell-Boswell M, Porter G, Bennett W (1976) A light and electron microscopic analysis of gentamicin nephrotoxicity in rats. Am J Pathol 82: 589–612Google Scholar
  6. 6.
    Leaback DH, Walker PG (1961) Studies on glucosaminidase. 4. The fluorimetric assay of N-acetyl-beta-glucosaminidase. Biochem J 78: 151–156Google Scholar
  7. 7.
    Litwack G (1955) Photometric determination of lysozyme activity. Proc Soc Exp Biol Med 89: 401–403Google Scholar
  8. 8.
    Luft FC, Franklin LI, Sloan RS, Yum MN (1978) Recovery from aminoglycoside nephrotoxicity with continued drug administration. Antimicrob Agents Chemother 14: 284–287Google Scholar
  9. 9.
    Manuel Y, Revillard JP (1970): Study of urinary proteins by zone electrophoresis. In: Manuel Y, Revillard JP, Betuel H (eds) Proteins in normal and pathological urine. S Karger, Basel, pp 153–171Google Scholar
  10. 10.
    Manuel Y, Laterre EC (1970) Tubular proteinuria: biochemical assay. In: Manuel Y, Revillard JP, Betuel H (eds) Proteins in normal and pathological urine. S Karger, Basel, pp 172–187Google Scholar
  11. 11.
    Manuel Y, Colle A, Leclercq M, Tonnelle C (1975) Low molecular weight proteinuria. Contr Nephrol 1: 156–162Google Scholar
  12. 12.
    Mattenheimer H (1977) Enzymes in renal diseases. Ann Clin Lab Sci 7: 422–432Google Scholar
  13. 13.
    Merle L, Charmes JP, Valette JP, Lachâtre G, Nicot G (1980) Urinary low molecular weight proteins as markers of early aminoglycoside nephrotoxicity in man. Drug induced renal failure: Satellite symposium to the Second International Congress of Toxicology, Montpellier, FranceGoogle Scholar
  14. 14.
    Merle LJ, Reidenberg MM, Camacho MT, Jones BR, Drayer DE (1980) Renal injury in patients with rheumatoid arthritis treated with gold. Clin Pharmacol Ther 28: 216–222Google Scholar
  15. 15.
    Mondorf AW, Hendus J, Beier J, Scherberich JE, Schoeppe W (1978) Tubular toxicity induced by aminoglycosides in human kidneys. In: Fillastre JP (ed) Nephrotoxicity. Masson, Paris New York, pp 167–174Google Scholar
  16. 16.
    Nagel W, Willig F, Schmitt FH (1964) Über die Aminosäurearylamidase — (sog. Leucinaminopeptidase) — aktivität im menschlichen Serum. Klin Wochenschr 42: 447–449Google Scholar
  17. 17.
    Nicot G, Charmes JP, Valette JP, Merle L, Dany F, Brosset P, Lachâtre G (1980) Signes urinaires précoces de néphrotoxicité des aminosides. Thérapie 35: 369–374Google Scholar
  18. 18.
    Nicot G, Merle L, Charmes JP, Valette JP, Lachâtre G (1980) Lysozymuria and gentamicin nephrotoxicity. N Engl J Med 303: 48Google Scholar
  19. 19.
    Pesce AJ, First MR (1979) Proteinuria. An integrated review. Marcel Dekker, New York, pp 32–53Google Scholar
  20. 20.
    Pesce AJ, First MR (1979) Proteinuria. An integrated review. Marcel Dekker, New York, pp 54–79Google Scholar
  21. 21.
    Pesce AJ, First MR (1979) Proteinuria. An integrated review. Marcel Dekker, New York, pp 175–201Google Scholar
  22. 22.
    Peterson PA, Evrin PE, Berggard I (1969) Differentiation of glomerular, tubular and normal proteinuria: determination of urinary excretion of beta 2 — microglobulin, albumin and total protein. J Clin Invest 48: 1189–1198Google Scholar
  23. 23.
    Price RG, Dance N (1967) The cellular distribution of some rat kidney glycosidases. Biochem J 105: 877–883Google Scholar
  24. 24.
    Revillard JP, Manuel Y, Francois R, Traeger J (1970) Renal diseases associated with tubular proteinuria. In: Manuel Y, Revillard JP, Betuel H (eds) Proteins in normal and pathological urine. S Karger, Basel, pp 209–219Google Scholar
  25. 25.
    Uriel J (1966) Méthode d'électrophorèse dans des gels d'acrylamide-agarose. Bull Soc Chim Biol 48: 969–982Google Scholar
  26. 26.
    Valette JP, Nicot G, Charmes JP, Merle L, Bennevent D, Leroux-Robert C (1979) Low molecular weight proteins as urinary markers of aminoglycoside nephrotoxicity in man. Proc Eur Dial Transplant Assoc 16: 597–602Google Scholar
  27. 27.
    Wellwood JM, Ellis BG, Price RG, Hammond K, Thompson AE, Jones NF (1975) Urinary N-acetyl-beta-d-glucosaminidase activities in patients with renal diseases. Br Med J 3: 408–411Google Scholar
  28. 28.
    Wellwood JM, Davies D, Leighton M, Thompson AE (1978) Urinary N-acetyl-beta-d-glycosaminidase in renal transplant recipients. Transplantation 26: 396–400Google Scholar

Copyright information

© Springer-Verlag 1982

Authors and Affiliations

  • G. Nicot
    • 1
  • L. Merle
    • 1
  • J. -P. Valette
    • 1
  • J. -P. Charmes
    • 1
  • G. Lachâtre
    • 1
  1. 1.Service de Pharmacologie CliniqueHôpital DupuytrenLimogesFrance

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