There are a wide variety of laboratory tests available to assess damage to and functional impairment of the kidneys, although the effectiveness of these tests varies greatly depending upon the site specificity of the damage and to a lesser extent upon the animal species involved.
Several traditional tests of renal dysfunction and damage, including plasma creatinine and urea, and urinalysis (dipstick andlor quantitative protein), can be used in the first instance to detect nephrotoxicity. A second tier of specific, targetted indicators (concentration test, urinary enzymes, clearance of analytes, specific proteins, etc.) may then be applied to identify further the site of the lesion and the functional status of the kidneys.
The glomerular filtration rate (CFR) may be estimated from the clearance of exogenous and endogenous substances. The difficulty in obtaining accurately timed urine samples limits the value of these tests in small animals, although methods that do not involve urine collection are available.
The kidney is the origin of several enzymes found in urine that can be used to monitor the toxic effects of chemicals and therapeutic substances. Selective measurement of enzyme activities in urine can be used to detect the site of the renal lesion after traditional tests have established the presence of renal injury. Separation of proteins in urine by electrophoretic techniques may also be used to discriminate damage to different parts of the nephron.
Renal cell excretion in urine is a sensitive but unreliable indicator of acute damage to the proximal tubule. The rate of cell excretion is not a good predictor of the severity of tubular injury.
The tests available, and their use in toxicological investigations, have been reviewed in the light of current practice in the UK.
* This paper has been prepared on behalf of and reviewed by the memhership of the Animal Clinical Chemistry Association of the UK. The opinions expressed are a consensus view and do not neccwrily represent the views of any individual member.
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and FZur which exert a regulatory effect on sodium homeostasis.
A comparison of several animal species reveals a wide range of kidney and body weights (Table 1). However, the number of nephrons, normalized to body weight change to a much lesser extent, and the dimensions of the nephron (glomerular radius. proximal tubular length and radius) appear remarkably constant from one species to another.4
Many chemical substances are known to influence renal function. The ability to produce mild and reversible changes is often of importance from a pharmacological viewpoint, e.g. diuretics or reninangiotensin inhibitors; however, irreversible changes may be produced following exposure to drugs and other chemicals. There are several factors that predispose the kidney, and in particular the proximal tubule, to injury. Firstly, because the blood supply to the kidneys is large, ca. 25% of cardiac output, it is possible for a high concentration of a toxic substance to be delivered to the kidneys, especially to the cortex. Secondly. since the kidneys have the ability not only to remove foreign substances from plasma but also subsequently to reabsorb or secrete them. then the concentration of