Acetaminophen-Induced Acute Kidney Failure
Acetaminophen is a commonly used medicine for pain-relief. During cold and flu season, it is common to resort to pain-relief medicines to relieve headaches, and ache and pain symptoms associated with a cold or flu as there is no cure. However, the therapeutic range for acetaminophen is 10-30 mg/l, which is small and very easy to go over. During cold and flu season, it is important to monitor the amount of paracetamol entering your body as acetaminophen is more dangerous than suspected. At therapeutic levels, acetaminophen does not produce any adverse effects, however, long-term treatment, prolonged use, and taking a few more than the recommended dose can be severely damaging and fatal. Accidental acetaminophen overdose took the lives of 1,500 people in the U.S between 2001 and 2010. The Randox Acetaminophen assay is used to determine the concentration levels of acetaminophen in the blood to determine if an overdose has taken place.
It is commonly recognised that acetaminophen overdose causes hepatotoxicity, but it is less commonly recognised that it can also cause nephrotoxicity in less than 2% of patients. Nephrotoxicity is toxicity of the kidneys and is often associated with a reduced amount of glutathione which is important for normal cellular metabolism in the kidneys. The Randox Glutathione Reductase assay is required for the regeneration of reduced glutathione. Glutathione is often discussed in association with the Randox Glutathione Peroxidase, which requires reduced glutathione for activation. Both Glutathione reagents are unique to Randox.
Acute renal failure due to acetaminophen manifests as acute tubular necrosis, which can occur alone or in combination with hepatic necrosis. Nephrotoxicity can also occur when the therapeutic levels of acetaminophen are not exceeded. This most commonly occurs when acetaminophen is taken in combination with alcohol. Upon testing acetaminophen levels and the results fall within the therapeutic range, the Randox Ethanol assay can test alcohol levels to determine if a combination of alcohol and acetaminophen caused nephrotoxicity. Renal impairment may be more common than previously suspected as acute renal failure occurs in 10-40% of patients with severe hepatic necrosis. Upon testing acetaminophen to determine toxicity, Randox also offer the following renal tests to test for nephrotoxicity:
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So far in our inflammatory biomarker series, we have considered the clinical significance of measuring rheumatoid factor (RF) and C-reactive protein (CRP) to detect inflammation. Inflammation, either chronic or acute, is the body’s immune response to protect against harmful stimuli such as damaged cells, irritants or pathogens and can be present in a range of diseases and conditions.1 Measuring inflammatory biomarkers can assist clinicians in the identification of a particular disease or can provide a marker of treatment response. In this blog, we consider the role of antioxidants and identify relevant biomarkers which may be linked to inflammatory states.
What is an antioxidant?
An antioxidant is a molecule that inhibits the oxidation of other molecules. Oxidation is a chemical reaction that produces free radicals, which are groups of very reactive molecules that can interrupt important cellular processes. Antioxidants are commonly referenced with regards to food, however antioxidants are also found in the body in the form of enzymes. Their purpose is to protect against the effects of oxidative stress to reduce damage from free radicals.
What is the link between antioxidants and inflammation?
Oxidative stress and the inflammation associated with it are the cause of most human disease. This would suggest that free radicals are implicated in many disease states for example rheumatoid arthritis, asthma, stroke, or cancer. Therefore antioxidants are important to protect against oxidative damage, thus reducing the risk of inflammation. There are a number of antioxidants which play a protective role the body, such as ferritin, superoxide dismutase, transferrin, uric acid and glutathione reductase.
Ferritin is responsible for storing iron and releasing it when required. Ordinarily, ferritin is found inside blood cells with only a small amount circulating in the blood. Ferritin is clinically significant at both high and low levels. Low levels of ferritin can highlight an iron deficiency which causes anaemia. Whereas elevated levels of ferritin can be a result of conditions such as rheumatoid arthritis, haemochromatosis, liver disease, metabolic syndrome, type 2 diabetes and renal failure.2 As ferritin is an acute phase reactant, levels will be elevated in any inflammatory state within the body.3
Transferrin is a protein that is responsible for binding and transporting iron in the blood. Transferrin acts as a preventative antioxidant as it binds with free iron, removing it from the bloodstream. This is a critical function, as free iron can stimulate the production of harmful free radicals. As transferrin is a negative acute phase protein, lower levels are associated with inflammatory conditions.7
Superoxide is a by-product of oxygen metabolism and is one of the most damaging free radicals in the body as it can cause cell damage. Superoxide Dismutase (SOD) is an enzyme which catalyses the breakdown of superoxide into a less damaging oxygen or hydrogen peroxide. Therefore SOD preforms a vital defensive function to reduce oxidative stress.4 Extensive research exists which links oxidative stress to chronic inflammation, which can be a contributing factor to diabetes, arthritis, cardiovascular disease and cancer.5 Therefore if levels of superoxide dismutase are low, patients are at risk inflammation, for example, SOD levels are significantly less in rheumatoid arthritis patients.6
Glutathione reductase is found in red blood cells and plays a key role in maintaining cell function and preventing oxidative stress in human cells. Reduced levels of glutathione reductase can contribute to the prevalence of inflammatory states, suggesting that adequate levels of glutathione reductase are essential for optimal function of the immune system. 7, 8
Uric acid is a waste product produced when the body breaks down chemical compounds called purines. It is a scavenging antioxidant that acts by inactivating free radicals. Elevated levels of uric acid is commonly associated with gout, a type of arthritis which is caused when crystals of sodium urate form inside joints causing rapid and painful inflammation.9 Other research has indicated that elevated levels of uric acid is associated with increased risk of cardiovascular disease.
Total Antioxidant Status (TAS)
TAS is a measurement of antioxidant function rather than quantity and considers the cumulative effect of all antioxidants present. The antioxidant defence system has many components, and a deficiency in any of these components can cause a reduction in the overall antioxidant status of an individual.10 Reduction in total antioxidant status has been implicated in several disease states including cancer, CVD, Arthritis and Alzheimer’s disease.
As demonstrated above, different types of antioxidants can help reduce different types of inflammation. Antioxidant tests can be requested from any doctor, who may also review dietary intake, investigate any symptoms and advise if testing is required. If antioxidant levels are found to be inadequate, improving them can be easily done through dietary changes, and can help reduce a body’s overall inflammation.
For health professionals
Randox Laboratories offer a range of diagnostic reagents for antioxidant testing to assist in the diagnosis of inflammatory diseases. Randox offer a complete diagnostic package with applications for a range of biochemistry analysers and a selection of kit sizes, controls and calibrators available. Available tests include: Ferritin, Transferrin, Superoxide Dismutase (Ransod), Glutathione Reductase, Uric Acid, and Total Antioxidant Status (TAS).
- Nordqvist, C., Inflammation: Causes, Symptoms and Treatment. Medical News Today, 2015, https://goo.gl/rT4WS9 (accessed 16 January 2017)
- Koperdanova, M., Interpreting raised serum ferritin levels, British Medical Journal, 2015, https://doi.org/10.1136/bmj.h3692 (accessed 2 February 2017)
- Nall, R. Ferritin Level Blood Test, Health Line, 2015, https://goo.gl/XGcW9P (accessed 2 February 2017)
- Yasui, K. and Baba, A., Therapeutic potential of superoxide dismutase (SOD) for resolution of inflammation. Inflammation Research. Vol.55, No.9, pp.359-363, 2006, 1007/s00011-006-5195-y (accessed 2 February 2017)
- Reuter, S., Gupta, S.C., Chaturvedi, M.M., Aggarwal, B.B., Oxidative stress, inflammation and cancer: How are they linked? Free Radic Biol Med. 2010, 1; 49(11):1603-1616 https://goo.gl/Uez3JZ (accessed 2 February 2017)
- Bae SC, Kim SJ, Sung MK., Inadequate antioxidant nutrient intake and altered plasma antioxidant status of rheumatoid arthritis patients. J Am Coll Nutr. 2003 Aug;22(4):311-5
- Reynolds, B., Glutathione for inflammatory respsonse, FX Medicine, 2015, Available from: https://goo.gl/2YAv5l (accessed 3 February 2017)
- Morris, G., Anderson, G., Dean, O. et al., The glutathione system: a new drug target in neuroimmune disorders. Mol Neurobiol 2014;50(3):1059-1084, Available from: https://goo.gl/PDSgwv (accessed 3 February 2017)
- Malaghan Institute, Uric acid – a new look at an old marker of inflammation, Malaghan Institute of Medical Research, 2013, Available from: https://goo.gl/P6NfXP
- Li, Y., Browne, R.W., Bonner, M.R., Deng, F., Tian, L., Mu, L., Positive Relationship between Total Antioxidant Status and Chemokines Observed in Adults. Oxid Med Cell Longev. 2014, Available from: https://goo.gl/rmj5MB (accessed 9 February 2017)