Skip to main content
Log in

Nephrotoxicity screening in rats; general approach and establishment of test criteria

  • Original Investigations
  • Published:
Archives of Toxicology Aims and scope Submit manuscript

Abstract

The concept of a nephrotoxicity screening test that is based on quantitative assessment of urine collected under standardized conditions for 15.5 h is presented. One to eight urine collections were performed in large numbers of untreated female Sprague-Dawley rats. Normal values for water consumption, urine volume, pH, and excretion of protein, gamma-glutamyltranspeptidase, malate dehydrogenase, electrolytes, glucose, amino acids, leukocytes, erythrocytes, epithelia, unspecified cells and cylinders were determined. Test criteria were established based on the statistical distribution of these measurements. In rats repeatedly placed in metabolism cages, a statistically significant decrease in leukocyte excretion and an increase in excretion of epithelia and unspecified cells were observed. All other variables did not change with time.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Alden CL (1986) A review of unique male rat hydrocarbon nephropathy. Toxicol Pathol 14: 109–111

    Google Scholar 

  • Balazs T (1974) Development of tissue resistance to toxic effects of chemicals. Toxicology 2: 247–255

    Google Scholar 

  • Bovee KC (1986) Renal function and laboratory evaluation. Toxicol Pathol 14: 26–36

    Google Scholar 

  • Boylan JW (1979) Symposium on proteinuria and renal protein catabolism. Introduction. Kidney Int 16: 247–250

    Google Scholar 

  • Braun JR, Rico AG, Bernard P, Burgat-Sacaze V, Eghbali B (1978) La gamma-glutamyl transferase urinaire en toxicologie renale chez le rat. Bases de son utilisation-intéret lors de néphrite aigue. Toxicology 11: 73–82

    Google Scholar 

  • Diézi J, Biollaz J (1979) Renal function tests in experimental toxicity studies. Pharmacol Ther 5: 135–145

    Google Scholar 

  • Dixon WJ, Brown MB, Engelman L, Frane JW, Hill MA, Jennrich RI, Toporek JD (1983) BMDP Statistical Software, 1983 Printing with Additions, University of California Press

  • Endou H, Koseki C, Yamada H, Obara T (1986) Evaluation of nephrotoxicity using isolated nephron segments. In: Tanabe T, Hook JB, Endou H (eds), Nephrotoxicity of antibiotics and immunosuppressants. Elsevier Science Publishers B.V., Amsterdam, pp 207–216

    Google Scholar 

  • Fent K, Mayer E, Zbinden G (1988) Nephrotoxicity screening in rats; validation study. Arch Toxicol 61: 349–358

    Google Scholar 

  • Guarino AM, Miller DS, Arnold ST, Pritchard JB, Davis RD, Urbaneck MA, Miller TJ, Litterst CL (1979) Platinate toxicity: past, present, prospects. Cancer Treat Rep 63: 1475–1483

    Google Scholar 

  • Halman J, Miller J, Fowler JSL, Price RG (1986) Renal toxicity of propyleneimine: assessment by non-invasive techniques in the rat. Toxicology 41: 43–59

    Google Scholar 

  • Ishmael J, Lock EA (1986) Nephrotoxicity of hexachlorobutadiene and its glutathione-derived conjugates. Toxicol Pathol 14: 258–262

    Google Scholar 

  • Kramer RA, Boyd MR, Dees JH (1986) Comparative nephrotoxicity of MeCCNU and chlorozotocin: functional-structural correlations in the F344 rat. Toxicol Appl Pharmacol 82: 540–550

    Google Scholar 

  • Linton AL, Bailey RR, Turnbull DI (1972) Relative nephrotoxicity of cephalosporin antibiotics in an animal model. Can Med Assoc J 107: 414–416

    Google Scholar 

  • Naftalin L, Mitchell LP (1958) A new urinary preservative. Clin Chim Acta 3: 197–199

    Google Scholar 

  • Owen RA, Heywood R (1986a) Strain-related susceptibility to nephrotoxicity induced by aspirin and phenylbutazone in rats. Toxicol Pathol 14: 242–246

    Google Scholar 

  • Owen RA, Heywood R (1986b) Age-related variations in renal structure and function in Sprague-Dawley rats. Toxicol Pathol 14: 158–167

    Google Scholar 

  • Peter CP, Burek JD, Zwieten MJ van (1986) Spontaneous nephropathies in rats. Toxicol Pathol 14: 91–100

    Google Scholar 

  • Prescott LF, Brodie DE (1964) A simple differential stain for urinary sediment. Lancet II: 940

    Google Scholar 

  • Price RG (1982) Urinary enzymes, nephrotoxicity and renal disease. Toxicology 23: 99–134

    Google Scholar 

  • Roy AK, Neuhaus OW (1967) Androgenic control of a sex-dependent protein in the rat. Nature 214: 618–620

    Google Scholar 

  • Sharratt M, Frazer AC (1963) The sensitivity of function tests in detecting renal damage in the rat. Toxicol Appl Pharmacol 5: 36–48

    Google Scholar 

  • Stroo WE, Hook JB (1977) Enzymes of renal origin in urine as indicators of nephrotoxicity. Toxicol Appl Pharmacol 39: 423–434

    Google Scholar 

  • Thouin MH (1983) Der Wert von qualitativen, semiquantitativen und quantitativen Bestimmungen im Rattenharn zum Nachweis tubulärer Nierenschädigungen. Diss. ETH Nr. 7296

  • Wormser U, Zbinden G (1985) Determination of primary amines in rat urine and plasma. Clin Chem 31: 1079–1080

    Google Scholar 

  • Zbinden G (1964) Anti-infective agents — the sulfa drugs. In: Molecular modification in drug design. Advances in chemistry series, no 45. American Chemical Society, pp 25–38

  • Zbinden G (1969) Experimental renal toxicity. In: Rouiller C, Müller AF (eds) The kidney. Morphology, biochemistry, physiology, vol II. Academic Press Inc., New York, pp 401–475

    Google Scholar 

  • Zbinden G, Elsner J, Boelsterli UA (1984) Toxicological screening. Regul Toxicol Pharmacol 4: 275–286

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zbinden, G., Fent, K. & Thouin, M.H. Nephrotoxicity screening in rats; general approach and establishment of test criteria. Arch Toxicol 61, 344–348 (1988). https://doi.org/10.1007/BF00334614

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00334614

Key words

Navigation