Discontinuation of the Acetest for Confirmation of Urinary Ketones

Monday, May 21, 2018

Measurement of urinary ketones is most frequently used to detect or confirm ketoacidosis in dogs and cats with diabetes mellitus or ketosis in ruminants. The dipstick pad reaction for ketones detects acetoacetate in particular and is less sensitive to acetone. β-hydroxybutyrate (BHB), the main ketone produced by the body, is not detected with the reaction. We used to perform the Acetest® routinely on any urine sample that yielded a positive result for ketones on the dipstick in order to verify the result. The Acetest® was a tablet version of the urinary dipstick pad reaction for ketones.

The rationale for the use of this tablet test was that the routinely dark color of animal urine samples frequently resulted in a false positive reaction because the color change yielding a positive result on the dipstick was quite subtle. Such false positives due to urine color were less likely to occur with the tablet test because the color change was more obvious, due to the addition of a color enhancer, lactose1. Also the tablet test is reportedly more sensitive for the detection of ketones than the dipstick test, detecting 5 versus 10 mg/dl of acetoacetate1. When the results of the dipstick and tablet tests were discrepant, e.g. a positive result was obtained for ketones on the dipstick but no color change was evident with the Acetest®, we would default to the result on the tablet test and assume the dipstick result was a false positive due to the color of the urine or other interfering substances. The ketone reaction was then reported as negative.

Unfortunately, the manufacturers of the Acetest® have discontinued this product and we are now no longer able to verify results from the dipstick with this test. Thus, we will be reporting out all dipstick reactions for ketones, some of which may be false positive. We have performed some internal studies at Cornell University, which have shown that most trace reactions (5 mg/dL) are likely false positive reactions and some small (15 mg/dL) to moderate (50 mg/dL) may also be false positive reactions. Therefore, we are now adding the following standard comment to our urinalysis results.

A weak to small positive reaction for ketones on the dipstick (5 -15 mg/dL and rarely higher values) could be a false positive due to color interference with the pad. If confirmation of this result is desired, we recommend measurement of urinary BHB concentrations.

Note that BHB measurement is performed on our chemistry analyzer.

Interpretation of urinary ketone results

Ketonuria may be seen in animals that are undergoing fat metabolism for some reason, e.g. anorectic, starvation, insulin resistant or insulin deficient (diabetes mellitus).  Since there is a very low renal threshold for ketones (of any type), ketones spill into the urine before they accumulate in blood, therefore a ketonuria will precede a ketonemia. Thus, a high BHB in urine may not be associated with ketonemia. We have found that animals in negative energy balance and undergoing fat metabolism have urinary BHB concentrations >10 mg/dL, with values > 20 mg/dL being associated with diabetes mellitus.  As mentioned above, BHB was not actually detected with the Acetest® or dipstick reaction for ketones. Our internal studies have shown that there is little correlation between urinary BHB concentrations and ketone reactions (dipstick or tablet). Please refer to BHB for information on requesting this test on a urine sample. Ideally, urinary BHB testing should be performed concurrently with serum BHB testing for optimal interpretation of results.

In conclusion, most of the weak positive reactions for ketones on a dipstick (5 mg/dL) are likely false positive due to urine color interfering with the dipstick color pad. If a stronger positive reaction for urinary ketones is obtained on a dipstick, this result should be interpreted in conjunction with the known history and clinical signs of the patient, i.e. evidence of fasting or anorectic states associated with negative energy balance or diabetes mellitus would support a true positive result. To confirm a ketoacidosis in diabetic patients, blood gas or serum biochemistry analysis would be required (to identify a high anion gap metabolic acidosis characteristic of ketoacidosis).

1. Osborne CA and Stevens JB (1999) Urinalysis: A clinical guide to compassionate patient care. Bayer Corporation and Bayer AG Leverkusen.