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 25-28 September, 2018 | Singapore
 4. Serum creatinine is a functional marker thus it is “blinded” to kidney injury that is not accompa- nied by decreased kidney function. In the liver, different markers are indicative to liver injury compared to liver function. Increased activities of alanine aminotransferase for example indicate liver injury but are not indicative of liver function. Other markers (i.e., urea, glucose, cholesterol, albumin, Bilirubin, bile acids etc.) indicate pres- ence of liver failure. Thus the clinician is aware of the presence of liver injury and can intervene before failure ensues. Conversely, in the kid- ney, there are no readily available and sensitive markers of kidney injury, thus with the first indica- tion of kidney disease, substantial decrease in kidney function has already occurred.
5. Serum creatinine does not represent the sever- ity of the dysfunction until a steady-state has been reached. For example, if GFR drops to zero and serum creatinine is measured immediately, it will still be within the reference range. In time se- rum creatinine will increase but it will take days until steady state has been reached, and the se- verity of the injury can be accurately assessed. Consequently, substantial changes in GFR at the early stages of AKI are associated with relatively small changes in serum creatinine.
The above limitations of serum creatinine are being reflected by the findings of several studies in human medicine indicating that small, and even transient, increase in serum creatinine concentration in human patients is detrimental. In one study, as little as 0.5 mg/ dL increase in serum creatinine was associated with increased in-hospital mortality (1). In another study,
a transient increase in serum creatinine was also associated with increased odds ratio for in-hospital mortality (2). Finally, even a small and transient increase in serum creatinine in patients that were discharged from the hospital, was associated with the need for chronic dialysis over the ensuing three years (3). In a study of heatstroke in dogs, the median creatinine concentration was only mildly increased at presentation and third
of the dogs presented with normal serum creatinine
concentration (4), however, concurrent evaluation of kidney function using GFR measurement revealed that kidney function was markedly decreased. Moreover, when kidney injury was assessed using sensitive markers, presence of kidney injury was identified in 100% of the dogs (4).
The aforementioned limitations and studies imply that relying on serum creatinine as the only marker of kidney function does not provide the entire information needed to accurately assess kidney function. When relying on serum creatinine, AKI is characteristically recognized only when the disease is within the maintenance phase, when clinical signs are overt. This is one of the speculated reasons for the high mortality rate among animals with AKI, as late recognition of the disease provides only a narrow window of opportunity for therapy. In CKD, due
to the wide reference range, the nonlinear relationship between GFR and serum creatinine and because the disease is initially subclinical, the diagnosis is delayed until most of nephrons are already lost.
Improving the interpretation of serum creatinine
Understating renal physiology and the limitations of serum creatinine improves interpretation of serum creatinine concentration. As oppose to the common believe that serum creatinine does not increase until
75% of GFR is decreased, any decrease in GFR is expected in be reflected by an increase in serum creatinine concentration. Thus, following small trends
in serum creatinine concentration within the reference range increases its sensitivity. In fact the International Renal Interest Society defines Grade I AKI as 0.3 mg/
dL (26.4μmol/L) increase in creatinine concentration compared to the baseline, even when creatinine is
within the reference range. The same can be applied to animals with CKD. Once the baseline serum creatinine concentration is a known, 0.3 mg/dL increase in the same dog and under the same conditions (fasted sample, normal hydration status, same methodology) represent decrease in kidney function and presence of CKD, even if creatinine is still within the reference range. The normal baseline creatinine concentration for a specific dog should be determined in a relatively young age, when the dog is fasted and is well hydrated. Any subsequent measurements of creatinine should be related to the baseline concentration and not for the reference range of dogs.
One of the aforementioned limitations of serum creatinine relates to its variability among dog breeds (5). Therefore, increased awareness for the breed specific reference range can sensitize the clinician to elevated creatinine even if the latter is still within the reference range. For example, creatinine of 1.2 in a Yorkshire Terrier likely represents ~75% decrease in kidney function, despite the fact that it is well within the reference range of most laboratories. Conversely, a serum creatinine

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