When the kidneys are unable to excrete some normal body constituents at the usual
rate the retention of these materials leads to an increase in the plasma concentration e.g.
creatinine and urea. However urine rather than blood is the most useful body fluid for
the non-invasive investigation of nephrotoxicity. Although urine is a convenient medium
to sample it has to be recognized that the composition of urine can be influenced by
organs other than the kidneys. The composition of urine reflects pre-renal renal and postrenal
events which include alterations in hepatic function e.g. bilirubinuria changes in
carbohydrate metabolism e.g. glycosuria and changes in fatty acid metabolism e.g.
ketonuria. Simple tests involve the recording of urine colour and appearance. The normal
colour reflects the concentration of urochromes but this can be affected by the presence
of both endogenous or exogenous materials e.g. blood bilirubin porphyrins drugs dyes.
Several of the core urinary measurements e.g. glucose blood pH etc. can be evaluated
qualitatively and/or semi-quantitatively by the use of one of several commercial test
strips (or dipsticks). Certain pitfalls may be found with animal species as the test strips
are designed for use in human clinical practice. These pitfalls are related primarily to
sensitivity and/or specificity e.g. protein (Evans and Parsons, 1986; Allchin and Evans
1986b; Allchin et al., 1987). Urine volume and concentration may act as indicators of
nephrotoxicity. Many nephrotoxic agents can produce oliguria or polyuria. The latter
finding may be a desired pharmacological and reversible response however it may
indicate an inability by the kidneys to concentrate the tubular fluid. The renal
concentrating ability varies from species to species both the dog and rat can achieve a
maximum osmolality approximately twofold greater than in humans (Schmidt-Nielsen
and O’Dell, 1961).