Uric Acid in Comprehensive Metabolic Panel: An opinion

Tieng Viet

By <a href="//commons.wikimedia.org/wiki/User:Bobjgalindo" title="User:Bobjgalindo">Bobjgalindo</a> - <span class="int-own-work" lang="en">Own work</span>, CC BY-SA 4.0,

Uric acid is a byproduct of the breakdown of purines, which are compounds found in certain foods and in the body’s own cells. Normally, it is dissolved in the blood and excreted by the kidneys through urine. However, when it is overproduced or poorly eliminated uric acid can accumulate in the blood and cause hyperuricemia, a condition associated with various health problems¹.

 

Hyperuricemia is a well-known risk factor for gout, a type of inflammatory arthritis that occurs when uric acid crystals form in the joints and cause pain, swelling, and stiffness¹. Hyperuricemia can also lead to the formation of kidney stones, which are hard deposits of minerals and salts that can block the urinary tract and cause severe pain, infection, and kidney damage¹.

 

However, recent studies have suggested that uric acid is associated with and may play an active role in the development of metabolic diseases, such as obesity, diabetes, hypertension, dyslipidemia, and cardiovascular disease^2-5. These diseases are characterized by impaired glucose and lipid metabolism, insulin resistance, chronic inflammation, oxidative stress, and endothelial dysfunction, which can increase the risk of heart attack, stroke, and kidney failure^2-5.

 

Besides association studies some potential mechanisms have been established^2-5. Uric acid can induce inflammation by activating the NLRP3 inflammasome, a complex of proteins that triggers the release of pro-inflammatory cytokines, such as interleukin-1β and interleukin-18, which can impair insulin signaling and glucose uptake in the muscles and liver^2,3.

 

Uric acid can increase oxidative stress by reducing the bioavailability of nitric oxide, a molecule that dilates blood vessels and protects them from damage. This can impair endothelial function and increase blood pressure, as well as promote the formation of atherosclerotic plaques, which are fatty deposits that narrow and harden the arteries^2,4. It can inhibit the activity of AMP-activated protein kinase (AMPK), a key enzyme that regulates energy metabolism and cellular homeostasis. This can reduce fatty acid oxidation and increase lipogenesis, leading to fat accumulation in the liver and other tissues, as well as dyslipidemia, which is an abnormal level of cholesterol and triglycerides in the blood^2,5.

 

Uric acid can interfere with the renin-angiotensin-aldosterone system (RAAS), a hormonal system that regulates blood pressure, fluid balance, and electrolyte levels. This can increase the reabsorption of sodium and water by the kidneys, leading to hypertension and edema, as well as reduce the excretion of uric acid, creating a vicious cycle of hyperuricemia^2,4.

 

These findings supported the common use of uric acid blood level as biomarker in medical practices, not only gout but also other metabolic diseases discussed above. A consensus for its application in at-risk and/or asymptomatic patients is however lacking. Checking for uric acid is generally left at the discretion of the healthcare provider and his patient. Uric acid is not part of a regular Comprehensive Metabolic Panel⁶ until purposedly prescribed. Its utility in risk assessment and early diagnosis of metabolic diseases notwithstanding, the arguments employed against its inclusion in metabolic panels were usually made along the following lines:

 

Cost-effectiveness: Adding uric acid to the CMP would increase the cost of the test, and it is not clear whether the benefits of early identification would outweigh the costs.

 

Overdiagnosis: Adding uric acid to the CMP could lead to the overdiagnosis of hyperuricemia, which could result in unnecessary anxiety and treatment.

 

Lack of consensus on treatment: There is no consensus on the optimal treatment for hyperuricemia, and it is not clear whether treating hyperuricemia would prevent metabolic diseases.

 

More research is needed to resolve these concerns, especially to determine the causal relationship between uric acid and specific metabolic diseases^2-5, and the desirable range to minimize disease risk. On the other hand, it is also fair to ask how much longer we should wait for all research to be done for consensus expert opinions. Moreover, what is the cost to those asymptomatic patients who will eventually progress to full blown diseases because of inadequate early intervention? For example, wouldn’t it be better to know blood level of uric acid in asymptomatic patients and advise if necessary, diet and lifestyle change to restore acceptable levels. Both patients and healthcare professionals currently remain in the dark because uric acid is not a regular component of metabolic panels prescribed during a regular physical examination.

 

The current situation, which leaves ordering uric acid tests primarily at the discretion of the healthcare provider, might not adequately protect asymptomatic patients, especially the young ones. Government health agencies and relevant medical societies must upgrade their recommendations to include uric acid in metabolic panels for asymptomatic patients, at the very least for those with a family history of metabolic diseases.

 

References

 

¹High Uric Acid Level-Causes-Mayo Clinic

²Controlling Uric Acid – The Key to Metabolic Health

³Hao-lu Sun, Yi-wan Wu, He-ge Bian, Hui Yang, Heng Wang, Xiao-ming Meng, Juan Jin (2021). Function of Uric Acid Transporters and Their Inhibitors in Hyperuricemia. Front. Pharmacol.12, Art. 667753. https://doi.org/10.3389/fphar.2021.667753

⁴Uric Acid: A Key Player in Cardio, Brain, and Metabolic Diseases

⁵Masato Furuhashi (2020). New insights into purine metabolism in metabolic diseases: role of xanthine oxidoreductase activity. Am J Physiol Endocrinol Metab 319: E827–E834. doi:10.1152/ajpendo.00378.2020

⁶Comprehensive Metabolic Panel