Measurement. Creatinine concentrations can be measured by several methods. The alkaline picrate method is most commonly used. It measures
the rate of color development (typically orange) when creatinine is complexed with alkaline picrate. Results may tend to be
higher than those obtained with autoanalyzers that use an enzymatic method (e.g. i-Stat [Abaxis]) because of the presence of noncreatinine chromogens. The Jaffe reaction is a form of the alkaline picrate
method. Some autoanalyzers (including portable analyzers such as VetScan [Abaxis]) use an adaptation of the Jaffe reaction
that can separate creatinine from noncreatinine chromogens.3 Thus, results from different measurement techniques cannot be directly compared.
A number of plasma constituents can interfere with creatinine measurement in dogs and cats.4,5 High serum bilirubin concentrations (3 mg/dl) can falsely lower creatinine concentrations.4,5 Glucose, fructose, pyruvate, acetoacetate, uric acid, ascorbic acid, and plasma proteins can all cause the Jaffe colorimetric
assays to yield falsely high creatinine concentrations in people.3 As a rule, interfering chromogens increase the creatinine result by about 20%, but with some diseases, the interference
can be much greater. For example, people with diabetic ketoacidosis can have marked spurious elevations in serum creatinine
concentrations.3 Cefazolin can increase the serum creatinine concentration in dogs and cats by 50% to 300% when it is measured by using the
Jaffe reaction.5
With marked renal insufficiency, as serum creatinine concentrations rise, noncreatinine chromogens contribute proportionally
less to the total reaction.3,5
Noncreatinine chromogens do not affect the variability of plasma creatinine concentrations.3 Therefore, clinicians should be less concerned about noncreatinine chromogen interference when serum creatinine concentrations
are markedly elevated, and measurement methods using enzymatic reactions are less affected by interference from most substances
except bilirubin.4,5
Normal serum creatinine concentrations in dogs and cats vary depending on the laboratory used. Trends should be interpreted
from values from a single laboratory and its reference ranges because results from different laboratories cannot be precisely
compared.6
Limitations of measurement. Measurement is fast and inexpensive; however, a serum creatinine concentration has low sensitivity and specificity as an
endogenous marker of GFR. It is influenced not only by GFR but also by factors affecting creatinine production such as muscle
mass and cachexia. Young animals have lower creatinine concentrations, whereas males and well-muscled individuals have higher
concentrations. Greyhounds have slightly higher serum creatinine concentrations than do non-greyhounds.7 If a greyhound's GFR is normal, an increase in creatinine concentration is probably attributable to increased muscle mass.7 The serum creatinine concentration is not affected appreciably by diet.
Figure 2
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Creatinine is not metabolized and is excreted by the kidneys almost entirely by glomerular filtration. Its rate of excretion
is relatively constant in the steady state, and serum creatinine concentration varies inversely with GFR. However, this relationship
is curvilinear, and, consequently, in early renal dysfunction, a large change in GFR is associated with little or no change
in the plasma creatinine concentration (Figure 2). A good example of this has been demonstrated in dogs with experimentally induced hypothyroidism that exhibited a substantial
decrease in GFR without altered plasma creatinine concentrations.8 This highlights the limitation of measuring creatinine concentration to detect subclinical kidney disease.
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