Ketonuria

Ketonuria is a medical condition in which ketone bodies are present in the urine.

Ketonuria
Ketonuria using Bayer Ketostix
SpecialtyEndocrinology

It is seen in conditions in which the body produces excess ketones as an indication that it is using an alternative source of energy. It is seen during starvation or more commonly in type 1 diabetes mellitus. Production of ketone bodies is a normal response to a shortage of glucose, meant to provide an alternate source of fuel from fatty acids.

Pathophysiology

Ketones are metabolic end-products of fatty acid metabolism. In healthy individuals, ketones are formed in the liver and are completely metabolized so that only negligible amounts appear in the urine. However, when carbohydrates are unavailable or unable to be used as an energy source, fat becomes the predominant body fuel instead of carbohydrates and excessive amounts of ketones are formed as a metabolic byproduct. Higher levels of ketones in the urine indicate that the body is using fat as the major source of energy.

Ketone bodies that commonly appear in the urine when fats are burned for energy are acetoacetate and beta-hydroxybutyric acid. Acetone is also produced and is expired by the lungs.[1] Normally, the urine should not contain a noticeable concentration of ketones to give a positive reading. As with tests for glucose, acetoacetate can be tested by a dipstick or by a lab. The results are reported as small, moderate, or large amounts of acetoacetate. A small amount of acetoacetate is a value under 20 mg/dL; a moderate amount is a value of 30–40 mg/dL, and a finding of 80 mg/dL or greater is reported as a large amount.

One 2010 study admits that though ketonuria's relation to general metabolic health is ill-understood, there is a positive relationship between the presence of ketonuria after fasting and positive metabolic health.[2]

Causes

In non-diabetic persons, ketonuria may occur during acute illness or severe stress. Approximately 15% of hospitalized patients may have ketonuria, even though they do not have diabetes. In a diabetic patient, ketone bodies in the urine suggest that the patient is not adequately controlled and that adjustments of medication, diet, or both should be made promptly. In the non diabetic patient, ketonuria reflects a reduced carbohydrate metabolism and an increased fat metabolism.

Diagnosis

A wide variety of companies manufacture ketone screening strips. A strip consists of a thin piece of plastic film slightly larger than a matchstick, with a reagent pad on one end that is either dipped into a urine sample or passed through the stream while the user is voiding. The pad is allowed to react for an exact, specified amount of time (it is recommended to use a stopwatch to time this exactly and disregard any resultant colour change after the specified time);[3][4] its resulting colour is then compared to a graded shade chart indicating a detection range from negative presence of ketones up to a significant quantity. In severe diabetic ketoacidosis, the dipstix reaction based on sodium nitroprusside may underestimate the level of ketone bodies in the blood. It is sensitive to acetoacetate only, and the ratio of beta-hydroxybutyric to acetoacetate is shifted from a normal value of around 1:1 up to around 10:1 under severely ketoacetotic conditions, due to a changing redox milieu in the liver. Measuring acetoacetate alone will thus underestimate the accompanying beta-hydroxybutyrate if the standard conversion factor is applied.[5]

Urine
value		DesignationApproximate serum concentration
mg/dLmmol/L
0 NegativeReference range: 0.5-3.0[6]0.05-0.29[6]
1+ 5 (interquartile range
(IQR): 1–9)[7]		0.5 (IQR: 0.1–0.9)[8]
2+ Ketonuria[9]7 (IQR: 2–19)[7]0.7 (IQR: 0.2–1.8)[8]
3+ 30 (IQR: 14–54)[7]3 (IQR: 1.4–5.2)[8]
4+ Severe ketonuria[10]--

Screening

Screening for ketonuria is done frequently for acutely ill patients, presurgical patients, and pregnant women. Any diabetic patient who has elevated levels of blood and urine glucose should be tested for urinary ketones. In addition, when diabetic treatment is being switched from insulin to oral hypoglycemic agents, the patient's urine should be monitored for ketonuria. The development of ketonuria within 24 hours after insulin withdrawal usually indicates a poor response to the oral hypoglycemic agents. Diabetic patients should have their urine tested regularly for glucose and ketones, particularly when acute infection or other illness develops.

In conditions associated with acidosis, urinary ketones are tested to assess the severity of acidosis and to monitor treatment response. Urine ketones appear before there is any significant increase in blood ketones;[11] therefore, urine ketone measurement is especially helpful in emergency situations.

References
  1. Detection of Ketones and Monitoring of Diabetic Ketoacidosis-cov-7
  2. Nam-Seok J; et al. (December 2010). "Ketonuria after Fasting may be Related to the Metabolic Superiority". J Korean Med Sci. 25 (12): 1771–1776. doi:10.3346/jkms.2010.25.12.1771. PMC 2995232. PMID 21165293.
  3. "Ketone Testing-Barbara Davis Center for Diabetes" (PDF). Archived from the original (PDF) on 2010-05-30. Retrieved 2010-03-20.
  4. Measuring Ketones in Urine-Children With Diabetes
  5. Laffel, Lori (1999-11-01). "Ketone bodies: a review of physiology, pathophysiology and application of monitoring to diabetes". Diabetes/Metabolism Research and Reviews. 15 (6): 412–426. doi:10.1002/(sici)1520-7560(199911/12)15:6<412::aid-dmrr72>3.0.co;2-8. ISSN 1520-7560. PMID 10634967.
  6. PTS PANELS™ Ketone Test Strips Information paper PS-002588E Rev. 2 10/05 by Polymer Technology Systems
  7. Converted from molar values, using average of 103 g/mol as used in: PTS PANELS™ Ketone Test Strips Information paper PS-002588E Rev. 2 10/05 by Polymer Technology Systems, and subsequently rounded to same number of significant figures as molar value
  8. Taboulet, P.; Deconinck, N.; Thurel, A.; Haas, L.; Manamani, J.; Porcher, R.; Schmit, C.; Fontaine, J.; Gautier, J. (2007). "Correlation between urine ketones (acetoacetate) and capillary blood ketones (3-beta-hydroxybutyrate) in hyperglycaemic patients". Diabetes & Metabolism. 33 (2): 135–139. doi:10.1016/j.diabet.2006.11.006. PMID 17320448.
  9. Sekizawa, A; Sugito, Y; Iwasaki, M; Watanabe, A; Jimbo, M; Hoshi, S; Saito, H; Okai, T (2001). "Cell-free fetal DNA is increased in plasma of women with hyperemesis gravidarum". Clinical Chemistry. 47 (12): 2164–5. doi:10.1093/clinchem/47.12.2164. PMID 11719487.
  10. Burbos, Nikolaos; Shiner, Alice M.; Morris, Edward (2008). "Severe metabolic acidosis as a consequence of acute starvation in pregnancy". Archives of Gynecology and Obstetrics. 279 (3): 399–400. doi:10.1007/s00404-008-0715-3. PMID 18592261. S2CID 22767401.
  11. BMJ Student Archive-Glycosuria and Ketonuria
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