Featured Reagent – G6PDH
Featured Reagent – G6PDH
Featured Reagent | G6PDH
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Glucose-6-phosphate dehydorgenase (G6PDH/G6PD) deficiency is an x-linked and sex-linked metabolic disorder, commonly affecting men more so than women1. The G6PDH enzyme is critical for the proper functioning of red blood cells (RBC’s). Depleated levels of G6PDH can cause the premature destruction of RBC’s (haemolysis). If the bone marrow cannot compensate for the reduction in RBC’s, heamolyic anaemia can develop. It is important to note that a deficiency in the G6PDH enzyme is not enough to promote the onset of haemolysis, but rather additional factors are required to promote the onset of symptoms2.
Some of the common side effects of G6PDH deficiency include: paleness, dark urine, yellowing of the skin and whites of the eyes, a rapid heart rate and shortness of breath. Common triggers for the development of haemolytic anaemia in those who are G6PDH deficient include: bacterial and viral infections, certain drugs (medications and antibiotics to treat malaria), and favism (inhaling the pollen from fava plants and ingesting fava beans)3
G6PDH deficiency has been recognised as a significant cause of mild to severe jaundice in newborns. It has been noted that those with this disorder commonly will not experience any signs or symptoms making them unaware that they have the condition3.
Haemolytic Anaemia
Haemolytic anaemia is an umbrella term used to describe the premature destruction of red blood cells (RBC’s). This disorder encompasses numerous conditions including: autoantibodies, medications, underlying malignancy, bone marrow failure, infection and heredity conditions including sickle cell disease or haemoglobinopathies4 5.
The severity of haemolytic anaemia depends on whether the onset of haemolysis is gradual or rapid and on the extent of RBC destruction. Patients with mild haemolysis can be asymptomatic whereas the anaemia in severe haemolysis can be life-threatening and can cause angina and cardiopulmonary decompensation. Haemolytic anaemia is an intravascular phenomenon meaning that this type of haemolysis occurs within the blood vessels and is caused by the following conditions: prosthetic cardiac valves, glucose-6-phosphate dehydrogenase (G6PDH) deficiency, thrombotic thrombocytopenic purpura, disseminated intravascular coagulation, transfusion of ABO incompatible blood and paroxysmal nocturnal haemoglobinuria (PNH)6.
Heredity disorders can also cause haemolysis due to the erythrocyte membrane and haemoglobin abnormalities, and enzymatic defects. Some hereditary disorders include: G6PDH deficiency, hereditary spherocytosis and sickle cell anaemia6.
Glucose-6-phosphate dehydrogenase (G6PDH) is a cytosolic enzyme located on the X-chromosome found in bodily cells. G6PDH is involved in the normal processing of carbohydrates and plays a critical role in RBC, protecting them from damage and premature destruction. The two main products of G6PDH are ribose-5-phosphate which is important for DNA, the chemical cousin of RNA. The chemical reaction produces NADPH which protects bodily cells from reactive oxygen species1.
Benefits of the G6PDH Assay
A niche assay from Randox meaning that Randox are one of the only manufacturers to offer a G6PDH assay in an automated biochemistry format.
Superior stability of 4 weeks upon reconstitution and stored at +2°C to +8°C. Many other commercially available assays offer only 5 days stability, leading to product wastage.
Minimal interference as the sample pre-wash step included in the Randox G6PDH testing method serves to purify the sample, leading to no known interferences being observed.
Excellent correlation coefficient of r=0.99 when compared against other commercially available methods.
Lyophilised reagent for enhanced stability.
UV method
G6PDH controls offering a complete testing package.
Applications available detailing instrument-specific settings for the convenient use of the Randox G6PDH assay on a wide range of clinical chemistry analsyers.
References
[1] Croom, Edward. Progress in Molecular Biology and Translational Science. 2012. ISBN 9780124158139 / ISSN 1877-1173.
[2] National Organization for Rare Disorders. Glucose-6-Phosphate Dehydrogenase Deficiency. [Online] no date. [Cited: January 31, 2019.] https://rarediseases.org/rare-diseases/glucose-6-phosphate-dehydrogenase-deficiency.
[3] U.S. National Library of Medicine. Glucose-6-phosphate dehydrogenase deficiency. [Online] May 2017. [Cited: January 30, 2019.] https://ghr.nlm.nih.gov/condition/glucose-6-phosphate-dehydrogenase-deficiency.
[4] National Heart, Lung, and Blood Institute. Hemolytic Anemia. [Online] no date. [Cited: January 28, 2019.] https://www.nhlbi.nih.gov/health-topics/hemolytic-anemia.
[5] BMJ Publishing Group. Hemolytic anemia. BMJ Best Practice. [Online] March 2018. [Cited: January 28, 2019.] https://bestpractice.bmj.com/topics/en-us/98.
[6] Schick, Paul. Hemolytic Anemia. Medscape. [Online] December 29, 2018. [Cited: Janaury 28, 2018.] https://emedicine.medscape.com/article/201066-overview.
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Featured Reagent – sPLA₂-IIA
Featured Reagent | sPLA2-IIA
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Benefits
A niche assay from Randox which means that Randox is one of the only manufacturers to offer an sPLA2-llA mass assay in an automated biochemistry format
Applications available detailing instrument-specific settings for the convenient use of the Randox sPLA2-IIA assay on a wide range of clinical chemistry analysers
Complementary controls and calibrators available offering a complete testing package
Automated assay which removes the inconvenience and time consumption associated with traditional ELISA based testing
Excellent correlation coefficient of r = 0.95 when compared against other commercially available methods
Liquid ready-to-use format for convenience and ease of use
Latex enhanced immunoturbidimetric method delivers high performance and confidence in results
NOTE: sPLA2 -IIA Assay – For Research Use Only
Clinical Significance
sPLA2-llA production of fatty acids and biologically active phospholipids plays an important role in platelet, monocyte, and endothelial activation, processes known to be critical steps in atherogenesis.1
Unlike traditional cardiac biomarkers used to predict adverse outcomes in patients with acute coronary syndrome (ACS), sPLA2-llA has been shown to act at multiple pathways involved in atherogenesis, from lipid oxidation to modulation of vascular & inflammatory cell activation and apoptosis.2
Biological Significance of sPLA2-IIA
Key observations through research has found that sPLA2-llA mediated modification of lipoproteins plays a role in the development of atherosclerosis. The surface of both low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) is surrounded by phosphatidylcholine (PC) a type of phospholipid which has been scientifically proven to serve as a good extracellular target for several isoforms of sPLA2-llA. sPLA2-llA works by hydrolysing these phospholipids resulting in the production of free fatty acids and lysophophatidylcholine (LPC) which can generate pro-inflammatory actions, accelerating atherosclerosis.1
Hydrolysis of LDL-C correlates with the production of the more atherogenic, small dense LDL cholesterol (sdLDL-C). The sPLA2-llA -processed low-density lipoprotein (LDL) contains a large amount of lysophospholipids and exhibit the property of “small-dense” or “modified” LDL, which facilitates foam cell formation from macrophages. Research has shown that high plasma levels of sdLDL-C compared to less dense, larger LDL-C create a higher risk of coronary heart disease.
Cardiovascular Disease
Regular cardiovascular screening is important to ensure that cardiac risk factors are detected at the earliest possible stages. Cardiovascular disease (CVD) encompasses a number of diseases of the heart and blood vessels. Four of the main types of CVD include: coronary heart disease (CHD), cerebrovascular disease (CVA), peripheral arterial disease (PAD) and aortic disease. It is vital that at risk patients are diagnosed as quickly and efficiently as possible to ensure effective treatment plan implementation.4
The early diagnosis of CVD aids in reducing the risk of a secondary cardiovascular event and to ensure the patient receives appropriate treatment to prevent premature deaths. Early risk assessment is particularly important in people who are at a greater risk of CVD. This is evaluated through the identification of one or more risk factors including: hypertension, diabetes or hyperlipidaemia. 3 ,5
It is believed that by 2030, almost 23.6 million people will die from CVD, mainly CHD and CVA, and is projected to remain the single leading cause of death. This provides further confirmation that early diagnosis is vital to prevent and reduce the number of deaths attributed to CVD.3
Biological Significance of sPLA2-IIA
Key observations through research has found that sPLA2-llA mediated modification of lipoproteins plays a role in the development of atherosclerosis. The surface of both low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) is surrounded by phosphatidylcholine (PC) a type of phospholipid which has been scientifically proven to serve as a good extracellular target for several isoforms of sPLA2-llA. sPLA2-llA works by hydrolysing these phospholipids resulting in the production of free fatty acids and lysophophatidylcholine (LPC) which can generate pro-inflammatory actions, accelerating atherosclerosis.1
Hydrolysis of LDL-C correlates with the production of the more atherogenic, small dense LDL cholesterol (sdLDL-C). The sPLA2-llA -processed low-density lipoprotein (LDL) contains a large amount of lysophospholipids and exhibit the property of “small-dense” or “modified” LDL, which facilitates foam cell formation from macrophages. Research has shown that high plasma levels of sdLDL-C compared to less dense, larger LDL-C create a higher risk of coronary heart disease.
Cardiovascular Disease
Regular cardiovascular screening is important to ensure that cardiac risk factors are detected at the earliest possible stages. Cardiovascular disease (CVD) encompasses a number of diseases of the heart and blood vessels. Four of the main types of CVD include: coronary heart disease (CHD), cerebrovascular disease (CVA), peripheral arterial disease (PAD) and aortic disease. It is vital that at risk patients are diagnosed as quickly and efficiently as possible to ensure effective treatment plan implementation.4
The early diagnosis of CVD aids in reducing the risk of a secondary cardiovascular event and to ensure the patient receives appropriate treatment to prevent premature deaths. Early risk assessment is particularly important in people who are at a greater risk of CVD. This is evaluated through the identification of one or more risk factors including: hypertension, diabetes or hyperlipidaemia. 3 ,5
It is believed that by 2030, almost 23.6 million people will die from CVD, mainly CHD and CVA, and is projected to remain the single leading cause of death. This provides further confirmation that early diagnosis is vital to prevent and reduce the number of deaths attributed to CVD.3
References
[1] Secreted phospholipase A2, lipoprotein hydrolysis, and atherosclerosis: integration with lipidomics. Kei, Yamamoto, et al. 7, s.l. : Analytical and Bioanalytical Chemistry, 2011, Vol. 400.
[2] Circulatory secretory phospholipase A2 activity predicts recurrent events in patients with severe acute coronary syndromes. . Mallat, Ziad, Steg, Gabriel and Benessiano, Joelle. 7, s.l. : Journal of the American College of Cardiology, 2005, Vol. 46.
[3] World Health Organization. Cardiovascular Diseases. World Health Organization. [Online] World Health Organization, May 17, 2017. [Cited: August 21, 2018.] https://www.who.int/news-room/fact-sheets/detail/cardiovascular-diseases-(cvds).
[4] National Health Service (NHS). Cardiovascular disease. [Online] September 17, 2018. [Cited: November 30, 2018.] https://www.nhs.uk/conditions/cardiovascular-disease/.
[5] National Institute for Health and Care Excellence (NICE). Cardiovascular disease risk assessment and prevention. [Online] no date. [Cited: ovember 30, 2018.] https://bnf.nice.org.uk/treatment-summary/cardiovascular-disease-risk-assessment-and-prevention.html.
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Niche Reagents – Zinc, Copper & Aldolase
Reagents | Zinc, Copper & Aldolase
Advancing Routine Testing with Randox Reagents
Randox offer an extensive range of 115 third party diagnostic reagents which are internationally recognised as being of the highest quality; producing accurate and precise results. Continually reinvesting in R&D, Randox continue to offer the opportunity to expand your test menu without expanding your lab. Not only does Randox offer superior performance assays, but also niche assays, meaning that Randox are one of the only manufacturers to offer the test in an automated biochemistry format.
Zinc
A niche assay from Randox meaning that Randox are one of the only manufacturers to offer a clinical chemistry zinc assay
Strong correlation with standard methods as the Randox zinc assay showed a correlation coefficient of r=0.9946 when compared against standard methods
A measuring range of 11.3 – 159 µmol/l for the comfortable and accurate detection of abnormal levels
Liquid ready-to-use reagents for convenience and ease-of-use
Stable to expiry date when stored at +15 to +25°C
Applications are available detailing instrument-specific settings for the convenient use of the Randox zinc assay on a wide range of clinical chemistry analysers
An essential trace metal and the only metal present in all enzyme classes, zinc is the second most abundant micronutrient in humans after iron. Zinc is required for a healthy immune system, a healthy growth rate during pregnancy, childhood and adolescence, wound health and synthesizing DNA. Zinc can modulate brain excitability and is vital in the synaptic plasticity of the brain which is thought to contribute towards memory and learning. Zinc has also been identified as a neurotoxin which suggests that zinc homeostasis is involved in the normal functioning of the central nervous system and the brain 1.
Zinc deficiency is identified as a malnutrition problem worldwide, especially in areas of high cereal intake and low animal food intake. However, other factors may contribute to low zinc levels including: the bioavailability of zinc, chronic illnesses such as diabetes, malignancy, hepatic disease and sickle cell disease. Higher zinc requirements have been identified in infants, children, adolescents, and pregnant and lactating women compared to adults. During periods of growth, zinc deficiency can result in growth failure. The most common organs affected by zinc deficiency clinically include: central nervous system, gastrointestinal, epidermal, skeletal, immune, and reproductive systems 2 3.
Copper
A niche assay from Randox meaning that Randox are one of the only manufacturers to offer a clinical chemistry copper assay
Exceptional correlation with standard methods as the Randox copper assay showed a correlation coefficient of r=0.99 when compared against standard methods
A wide measuring range of 6.6 – 86 µmol/l for the comfortable and accurate detection of abnormal levels
Lyophilised reagents for enhanced stability
Excellent stability of 2 weeks when stored at +2 to +8°C
Applications are available detailing instrument-specific settings for the convenient use of the Randox copper assay on a wide range of clinical chemistry analysers
An essential trace metal, copper is the third most abundant micronutrient in humans after iron and zinc. Copper is mainly found in the brain, liver, kidneys, heart and skeletal muscle with the highest quantities found in the liver and muscles. It aids in some of the key bodily functions including: the production of red blood cells, the maintenance of nerve cells and the immune system, the formation of collagen to absorb iron for energy production, and the formation of melanin, bone and connective tissue. Ceruloplasmin is the protein responsible for the transportation of copper around the body 4.
There are various health problems that can cause abnormal copper levels, however deficiency is less likely than toxicity because a normal diet contains plenty of copper including: organic meats, beans and wholegrains. Deficiency is more likely to occur in those who are malnourished, more likely children.
Deficiency more commonly occurs in premature babies, resulting in bone abnormalities and fractures. Menkes Disease is a rare inherited genetic disorder of copper metabolism and is characterised by sparse and kinky hair as children with this disorder are unable to absorb enough copper 5.
Toxicity can be caused by consuming too many dietary supplements high in copper, from drinking contaminated water, or from fungicides containing copper sulphates. Wilson disease is a rare inherited disorder that prohibits the liver from safely storing and excreting copper resulting in it seeping out of the liver and building up in the eyes, liver, kidneys and brain causing nerve damage, and if untreated, it can be fatal 6.
Aldolase
A niche assay from Randox meaning that Randox are one of the only manufacturers to offer a clinical chemistry aldolase assay
Excellent correlation coefficient of r=0.9917 when compared against other commercially available methods
A wide measuring range of 1.73 – 106 µmol/l for the comfortable and accurate detection of abnormal levels
Lyophilised reagents for enhanced stability
UV Method
Applications are available detailing instrument-specific settings for the convenient use of the Randox aldolase assay on a wide range of clinical chemistry analysers
There are three types of Aldolase enzymes that can be can be found throughout the body: A, B and C. It is responsible for converting glucose into energy.
A is primarily contained within the muscle and erythrocytes, whereas B is contained within the liver, enterocytes and kidney, and A and C can be found within the brain. Despite the Aldolase enzyme existing throughout the body, the highest concentration levels of it can be found in the liver and the skeletal muscle, although testing this enzyme is routinely used for skeletal muscle damage 7.
Elevated levels of type A aldolase in the blood can be found in patients with damage to the skeletal muscle as the result of a trauma which includes dermatpmyositis, infectious mononucleosis, muscular dystrophy, myocardial infarction, hepatic cancer due to the damaged cells triggering the release of A into the blood. On the other hand, the concentration levels of A in the blood remain normal in situations where weakness is caused as the result of a neurological disease such as multiple sclerosis. Measuring A concentration levels in the blood can therefore be used to determine the root cause of muscle weakness, whether muscle trauma or neurological myopathy, in patients 7.
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References
[1] Osredkar, Josko and Sustar, Natasa. Copper and Zinc, Biological Role and Significance of Copper/Zinc Imbalance. 1, s.l. : Journal of Clinical Toxicology, 2011, Vol. 3.
[2] Jockers, Dr. David. How To Test Zinc Levels At Home. DrJockers.com. [Online] 2019. [Cited: November 28, 2018.] https://drjockers.com/test-zinc-levels-home/..
[3] Roohani, Nazanin, et al. Zinc and its importance for human health: An integrative review. National Center for Biotechnology Information. [Online] J Res Med Sci, February 18, 2013. [Cited: November 28, 2018.] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3724376/..
[4] Nordqvist, Joseph. What are the health benefits of zinc? Medical News Today. [Online] December 5, 2017. [Cited: November 28, 2018.] https://www.medicalnewstoday.com/articles/263176.php.
[5] Macfarlane, Susan. Understanding Nutrient Ratios: Zinc/Copper. Susan Macfarlane. [Online] October 29, 2017. [Cited: November 28, 2018.] https://susanmacfarlanenutrition.com/understanding-nutrient-ratios-zinccopper/.
[6] National Center for Advancing Translational Sciences. Menkes disease. National Center for Advancing Translational Sciences. [Online] Genetic and Rare Disease Information Center, April 7, 2017. [Cited: November 30, 2018.] https://rarediseases.info.nih.gov/diseases/1521/menkes-disease.
[7] Berridge, Brian R, Van Vleet, John F and Herman, Eugene. Chapter 46 – Cardiac, Vascular, and Skeletal Muscle Systems. 2013.
Rare Disease Day: 28th February 2019
28th February 2019
Rare Disease Day: 28th February 2019
Rare Disease Day raises awareness of rare diseases and how patients’ lives are affected. Many rare diseases remain incurable and many go undiagnosed. 1 in 20 people will live with a rare disease at some point in their life and this is why it is so important to raise awareness.1
What is a rare disease?
There is no single definition for a rare disease, as many countries identify them differently. In the United States, the Rare Diseases Act of 2002 defines a rare disease by its prevalence: “any disease or condition that affects fewer than 200,000 people in the United States”. However, the EU defines a rare disease as a condition that affects less than 5 in 10,000 of the population. There are approximately 7000 rare diseases and disorders and 50% of people affected by rare diseases are children.2,3
Hyperlipoproteinemia type III
This rare disease day, Randox will be raising awareness of hyperlipoproteinemia type III. Hyperlipoproteinemia type III, also known as dysbetalipoproteinemia or broad beta disease, is a rare genetic disorder characterised by improper breakdown of lipids, specifically cholesterol and triglycerides. The condition is caused by mutations in the Apo-E gene, however the inheritance of this condition is complicated due to the development of symptoms having to be triggered by a secondary factor to raise lipid levels. These factors include diabetes, obesity or hypothyroidism.
It is unknown exactly what the prevalence of the condition is, but it is estimated to affect approximately 1 in 5,000 – 10,000 of the general population and it has been found that it affects males more often than females, with women rarely being affected until after menopause.4,5
Figure A. Example of cholesterol and lipid build-up [6]
Symptoms
Symptoms for hyperlipoproteinemia type III will vary for each individual and some people may even be asymptomatic. The most common symptom is the development of xanthomas which are deposits of fatty material, the lipids, in the skin and underlying tissue. Xanthomas may appear on the palms of the hands, eyelids, soles of the feet or on the tendons of the knees and elbows.
> Chest pain or other signs of coronary artery disease
> Cramps in the calves when walking
> Sores on toes
> Stroke-like symptoms such as trouble speaking, dropping on one side of the face, weakness in an arm or a leg and a loss of balance6
Complications can arise if the condition is left untreated and these can include: myocardial infarction, ischemic stroke, peripheral vascular disease, intermittent claudication and gangrene of the lower extremities.7
Diagnosis
Although there is no specific diagnostic test for hyperlipoproteinemia type III, diagnosis is based on clinical evaluation and identification of symptoms. Research has indicated that an algorithm comprising a number of dysbetalipoproteinemia indices may be helpful in the diagnosis of the disease. These include:
> Low apolipoprotein B to total cholesterol ratio
> Elevated levels of triglycerides
> Elevated levels of total cholesterol8
Managing the condition
The condition cannot be cured but treatment is to control conditions such as obesity, hypothyroidism and diabetes. Most patients will go through dietary therapy to control their intake of cholesterol and saturated fat. This prevents xanthomas, high levels of lipids in the blood, exercise will also help to lower lipid levels. However, dietary changes may not be effective for some individuals and this is where drugs may be used to lower lipid levels instead.
How Randox can Help
Randox offer a range of routine and niche assays within the lipid testing panel to monitor lipid levels and to identify associated complications. Some of these tests include:
Apolipoprotein B
The Randox Apolipoprotein B tests utilises an immunoturbidimetric method, offers a wide measuring range and is available liquid ready-to-use for convenience and ease of use.
Total Cholesterol
The Randox Total Cholesterol test utilises the CHOD-PAP method and offers an extensive measuring range with a wide range of kits available to suit a wide range of laboratory sizes.
Triglycerides
The Randox Triglycerides test utilises the GPO-PAP method while offering an extensive measuring range with both liquid and lyophilised formats available offering choice and flexibility.
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References
[1] Rare Disease Day. What is Rare Disease Day? Rare Disease Day. [Online] 2019. [Cited: February 21, 2019.] https://www.rarediseaseday.org/article/what-is-rare-disease-day
[2] Genetic Alliance UK. What is a Rare Disease? Rare Disease UK. [Online] 2018. [Cited: February 21, 2019.] https://www.raredisease.org.uk/what-is-a-rare-disease/
[3] NZORD. Rare Disease Facts and Figures. NZORD. [Online] 2019. [Cited: February 21, 2019.] https://www.nzord.org.nz/helpful-information/rare-disease-facts-and-figures.
[4] NORD. Hyperlipoproteinemia Type III. NORD. [Online] 2019. [Cited: February 21, 2019.] https://rarediseases.org/rare-diseases/hyperlipoproteinemia-type-iii/
[5] GARD. Hyperlipidemia Type 3. National Centre for Advanciing Translational Sciences. [Online] December 29, 2016. [Cited: February 21, 2019.] https://rarediseases.info.nih.gov/diseases/6703/hyperlipidemia-type-3
[6] Falck, Suzanne. Everything you need to know about hyperlipidemia. Medical News Today. [Online] December 21, 2017. [Cited: February 21, 2019.] https://www.medicalnewstoday.com/articles/295385.php
[7] Medline Plus. Familial Dysbetalipoproteinemia. Medline Plus. [Online] May 16, 2018. [Cited: February 21, 2019.] https://medlineplus.gov/ency/article/000402.htm.
[8] Dysbetalipoproteinemia: Two cases report and a diagnostic algorithm. Kei, Anastazia, et al. 4, s.l. : World Journal of Clinical Cases, 2015, Vol. 3.
Obesity and Kidney Disease: What is the Connection?
30th January 2019
Obesity and Kidney Disease: What is the Connection?
The month of January has forever been the month of resolutions with many choosing to ditch the sweets and join the gym. However, for many these efforts are limited to January and bad habits are quick to remerge. Obesity has been a burden on the health service for many years with the problem, like many people’s waist lines, only continuing to expand.
Recent findings have shown that this problem is no longer just increasing in developed countries but also in developing countries. In fact, worldwide obesity has tripled since 1975. In 2016, more than 1.9 million adults were classed as overweight, of which over 650 million were obese.1 These are shocking statistics for a condition that is preventable. As a global concern, it is important to assess all the potential risks of this problem.
The most common diseases associated with obesity are cardiovascular disease (CVD) and diabetes. However, the associated risks are much greater than this. Being overweight may also increase the risk of certain types of cancer, sleep apnea, osteoarthritis, fatty liver disease and kidney disease.2
Obesity is now recognised as a potent risk factor for the development of renal disease.3 Excess weight has a direct impact on the development and progression of chronic kidney disease (CKD). Globally, the prevalence of diabetic kidney disease rose by 39.5% between 2005 and 2015, coinciding with the increased CKD prevalence.4 In obese individuals, the kidneys have to work harder, filtering more blood than normal to meet the metabolic demands of increased body weight, increasing the risk of kidney disease.
The traditional diagnostic test for renal impairment is creatinine. This test is carried out through the measurement of creatinine levels in the blood to assess the kidneys ability to clear creatinine from the body. This is called the creatinine clearance rate which helps to estimate the glomerular filtration rate (GFR), which is the rate of blood flow through the kidneys.5
Problems arise when using creatinine for CKD testing as a number of factors need to be taken into consideration including age, gender, ethnicity and muscle mass. For this reason, black men and women exhibit higher creatinine levels than white men and women, raising concern over the accuracy of this test for certain patient groups.6 In addition, serum creatinine is not an adequate screening test for renal impairment in the elderly due to their decreased muscle mass.7
The main disadvantage of using creatinine to screen for renal impairment is that up to 50% of renal function can be lost before significant creatinine levels become detectable as creatinine is insensitive to small changes in GFR. Consequently, treatment is not provided at the appropriate time which can be fatal, therefore, an earlier and more sensitive marker for renal function is vital.8
These disadvantages have not only been highlighted in research but also by the national institute for health and care excellence (NICE). NICE updated the classification of CKD in 2004 to include the albumin: creatinine ratio (ACR). They split chronic kidney disease patients into categories based on GFR and ACR. Figure 1 highlights the different categories and risk of adverse outcomes. NICE recommend using eGFR Cystatin C for people in the CKD G3aA1 and higher.9
Figure 1 Classification of Chronic Kidney Disease using GFR and ACR categories.9
Despite these suggestions, Creatinine is still being used for G3a1 and increasing risk levels.
The utility of cystatin C as a diagnostic biomarker for kidney disease has been documented to show superiority of traditional CKD tests. There is no ‘blind area’ making it very sensitive to small changes in GFR and capable of detecting early reductions. Furthermore, this marker is less influenced by diet or muscle mass and has proven to be a beneficial test in patients who are overweight.8
A number of studies support the statement: ‘Cystatin C levels are higher in overweight and obese patients’. This is important because when cystatin c levels are too high, it may suggest that the kidneys are not functioning properly. One study conducted, using a nationally representative sample of participants, found that overweight and obesity maintained a strong association with elevated serum cystatin C. This suggests that weight can affect the levels of cystatin C and therefore the likelihood of developing kidney disease.10
How Randox can Help
The Randox automated Latex Enhanced Immunoturbidimetric Cystatin C tests offers an improved method for assessing CKD risk, combined with a convenient format for routine clinical use, for the early assessment of at risk patients. Randox is currently one of the only diagnostic manufacturers who offer an automated biochemistry test for Cystatin C measurement, worldwide.
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References
- World Health Organization. Obesity and Overweight . int. [Online] WHO. [Cited: January 22, 2019.] https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight.
- Health Risks of Being Overweight. NIDDK. [Online] National Institute of Diabetes and Digestive and Kidney Diseases. [Cited: March 24, 2019.] https://www.niddk.nih.gov/health-information/weight-management/health-risks-overweight.
- Kidney Health Australia . Obesity and Chronic Kidney Disease: The Hidden Impact. Kidney Health Week/ World Kidney Day 2017. [Online] Kidney Health Australia. [Cited: January 22, 2019.] https://kidney.org.au/cms_uploads/docs/kidney-health-australia-report-obesity-and-chronic-kidney-disease–the-hidden-impact_06.03.17.pdf.
- Neuen, Brendon Lange, et al. Chronic kidney disease and the global NCDs agenda. s.l. : BMJ Global Health, 2017
- Creatinine and Creatinine Clearance Blood Tests. WebMD. [Online] WebMD. [Cited: January 22, 2019.] https://www.webmd.com/a-to-z-guides/creatinine-and-creatinine-clearance-blood-tests#1.
- Lascano, Martin E and Poggio, Emilio D. Kidney Function Assessment by Creatinine-Based Estimation Equations. Cleveland Clinic. [Online] August 2010. [Cited: 16 May 2018.] http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/nephrology/kidneyfunction/.
- Swedko, Peter J, et al. Serum Creatinine Is an Inadequate Screening Test for Renal Failure in Elderly Patients. Research Gate. [Online] February 2003. [Cited: 6 May 2018.] https://www.researchgate.net/publication/8243393_Serum_Creatinine_Is_an_Inadequate_ Screening_Test_for_Renal_Failure_in_Elderly_Patients.
- Mishra, Umashankar. New technique developed to detect chronic kidney disease. Business Line. [Online] 07 May 2018. [Cited: 17 May 2018.] https://www.thehindubusinessline.com/news/science/new-technique-to-detect-chronic-kidney-disease/article23803316.ece.
- National Institute for Health and Care Excellence. Chronic kidney disease in adults: assessment and management: 1 Recommendations. National Institute for Health and Care Excellence. [Online] January 2015. https://www.nice.org.uk/guidance/cg182/chapter/1- recommendations#classification-of-chronic-kidney-disease-2.
- Overweight and Obesity and Elevated Serum Cystatin C Levels in US Adults . Muntner, Paul, et al. 4, s.l. : NCBI, 2008, Vol. 121.
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Featured Reagent – Copper & Zinc
Featured Reagents | Copper & Zinc
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Nutrient Testing
Copper and zinc are essential trace minerals, found in all bodily cells and they are necessary for survival. Although, their roles within the body differ. Copper is essential to produce red blood cells and zinc is essential for the proper function of the immune system (1) (2). Whilst both of these nutrients exist naturally in the environment including water and food, both nutrients can exist in the body in higher or lower than normal concentrations which can cause major health complications (3).
Copper
A niche assay from Randox meaning that Randox are one of the only manufacturers of the clinical chemistry Copper assay
Exceptional correlation with standard methods as the Randox Copper assay showed a correlation coefficient of r=0.99 when compared against standard methods
A wide measuring range of 6.6 – 86 µmol/l for the comfortable and accurate detection of abnormal levels
Lyophilised reagents for enhanced stability
Excellent stability of 2 weeks when stored at +2 to +8°C
Applications are available detailing instrument-specific settings for the convenient use of the Randox Copper assay on a wide range of clinical chemistry analysers
Copper is mainly found in the brain, liver, kidneys, heart and skeletal muscle with the highest quantities found in the liver and muscles. It aids in some of the key bodily functions including: the production of red blood cells, the maintenance of nerve cells and the immune system, the formation of collagen to absorb iron for energy production, and the formation of melanin, bone and connective tissue. Ceruloplasmin is the protein responsible for the transportation of Copper around the body (4).
There are various health problems that can cause abnormal copper levels, however deficiency is less likely than toxicity because a normal diet contains plenty of copper including: organ meats, beans and wholegrains. Deficiency is more likely to occur in those who are malnourished, more likely children.
Deficiency more commonly occurs in premature babies, resulting in bone abnormalities and fractures. Menkes Disease is a rare inherited genetic disorder of copper metabolism and is characterised by sparse and kinky hair as children with this disorder are unable to absorb enough copper (5).
Toxicity can be caused by consuming too many dietary supplements high in copper, from drinking contaminated water, or from fungicides containing copper sulphates. Wilson disease is a rare inherited disorder that prohibits the liver from safely storing and excreting copper resulting in it seeping out of the liver and building up in the eyes, liver, kidneys and brain causing nerve damage, and if untreated, it can be fatal (6).
Zinc
A niche assay from Randox meaning that Randox are one of the only manufacturers of the clinical chemistry zinc assay
Strong correlation with standard methods as the Randox Zinc assay showed a correlation coefficient of r=0.9946 when compared against standard methods
A measuring range of 11.3 – 159 µmol/l for the comfortable and accurate detection of abnormal levels
Liquid ready-to-use reagents for convenience and ease-of-use
Stable to expiry date when stored at +15 to +25°C
Applications are available detailing instrument-specific settings for the convenient use of the Randox Zinc assay on a wide range of clinical chemistry analysers
Zinc is required for various biological processes including: cell and enzyme production; the functionality of enzymes, metabolism of carbohydrates, fat and protein from dietary intake; wound healing; and the stabilisation of DNA (7) (8).
Zinc deficiency is identified as a malnutrition problem worldwide, especially in areas of high cereal intake and low animal food intake. However, other factors may contribute to low zinc levels including: the bioavailability of zinc, chronic illnesses such as diabetes, malignancy, hepatic disease and sickle cell disease. Higher zinc requirements have been identified in infants, children, adolescents, and pregnant and lactating women compared to adults. During periods of growth, zinc deficiency can result in growth failure. The most common organs affected by zinc deficiency clinically include: central nervous, gastrointestinal, epidermal, skeletal, immune, and reproductive systems (9) (10).
References
[1] Ware, Megan. Health benefits and risks of copper. Medical News Today. [Online] October 23, 2017. [Cited: November 28, 2018.] https://www.medicalnewstoday.com/articles/288165.php.
[2] Medline Plus. Zinc in diet. Medline Plus. [Online] November 13, 2018. [Cited: November 28, 2018.] https://medlineplus.gov/ency/article/002416.htm.
[3] Jockers, Dr. David. Do You Have A Copper and Zinc Imbalance? DrJockers.com. [Online] 2017. [Cited: November 28, 2018.] https://drjockers.com/copper-zinc-imbalance/.
[4] Macfarlane, Susan. Understanding Nutrient Ratios: Zinc/Copper. Susan Macfarlane. [Online] October 29, 2017. [Cited: November 28, 2018.] https://susanmacfarlanenutrition.com/understanding-nutrient-ratios-zinccopper/.
[5] National Center for Advancing Translational Sciences. Menkes disease. National Center for Advancing Translational Sciences. [Online] Genetic and Rare Disease Information Center, April 7, 2017. [Cited: November 30, 2018.] https://rarediseases.info.nih.gov/diseases/1521/menkes-disease.
[6] Mayo Clinic. Wilson’s disease. Mayo Clinic. [Online] March 7, 2018. [Cited: November 30, 2018.] https://www.mayoclinic.org/diseases-conditions/wilsons-disease/symptoms-causes/syc-20353251.
[7] Frassinetti, S, et al. The roel of zinc in life: a review. National Center for Biotechnology Information. [Online] J Environ Pathol Toxicol Oncol, 2006. [Cited: November 28, 2018.] https://www.ncbi.nlm.nih.gov/pubmed/17073562..
[8] Jockers, Dr. David. How To Test Zinc Levels At Home. DrJockers.com. [Online] 2019. [Cited: November 28, 2018.] https://drjockers.com/test-zinc-levels-home/..
[9] Roohani, Nazanin, et al. Zinc and its importance for human health: An integrative review. National Center for Biotechnology Information. [Online] J Res Med Sci, February 18, 2013. [Cited: November 28, 2018.] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3724376/..
[10] Nordqvist, Joseph. What are the health benefits of zinc? Medical News Today. [Online] December 5, 2017. [Cited: November 28, 2018.] https://www.medicalnewstoday.com/articles/263176.php.
Featured Reagents Homepage
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Randox – Diabetes
During December, we aim to highlight how the Randox product portfolio can be used for accurate diagnosis and monitoring of diabetes, with a focus on the Randox Reagents diabetes panel which offers a total of 12 assays for accurate and reliable diabetes testing.
Diabetes is one of the leading causes of death worldwide and it is estimated by WHO (World Health Organisation) that 2.2 million additional deaths are being caused by the condition each year. The number of people with the condition has being growing rapidly in the last 30 years, the International Diabetes Federation predicts that approximately 438 million people will have diabetes by 2030. Early diagnosis and constant monitoring of diabetes is essential in order to manage the condition, as diabetes can lead to other health problems such as heart disease, kidney damage or failure, nerve damage and even blindness.
Randox knows that this condition cannot be ignored as each year it is increasingly becoming a burden on the health service. Randox Reagents are committed to advancing diabetes related testing and offer an extensive range of high quality reagents: from diabetes diagnosis, to the monitoring of diabetes-related complications, the Randox Reagents diabetes testing panel covers the full spectrum of clinical testing requirements.
Reagents Diabetes Testing Assays
To aid with the growing concern of diabetes, Randox Reagents offer a comprehensive range of 12 assays within their diabetes testing panel including assays for the diagnosis and monitoring of diabetes which includes fructosamine, glucose and HbA1c and also those which monitor diabetes-related complications such as adiponectin, cystatin c, microalbumin and NEFA. The Randox diabetes reagents offer a range liquid ready-to-use and lyophilised formats for increased efficiency, applications are also available for a wide range of biochemistry analysers.
RX series Direct HbA1c Testing Capabilities
Renowned for quality and reliability the RX series range of clinical chemistry analysers boasts a world leading test menu with an extensive range of high performing and unique assays available. In addition to NEFA, D-3-Hydroxybutyrate (Ranbut) and Fructosamine the RX series welcomes Direct HbA1c testing on the RX Daytona +, RX imola and RX modena. The latex enhanced immunoturbidimetric method improves laboratory performance and time, highly improving accuracy and precision by revolutionising your diabetes testing capabilities.
Quality Control
Designed for use in the Quality Control of both HbA1c and Total Haemoglobin assays, our Acusera HbA1c controls are an ideal match for laboratories running these parameters and POCT testing. Available in liquid ready-to-use or lyophilised formats, these controls offer attractive stability and flexibility for labs and healthcare practices of any size. Manufactured using human whole blood which ensures commutability, our controls directly mimic the performance of real patient samples helping deliver reliable results.
RIQAS Glycated Haemoglobin Programme
Designed to monitor the performance of HbA1c, our RIQAS glycated haemoglobin EQA program is suitable for both qualitative and quantitative methods of analysis. As the largest EQA scheme in the world, access to large peer groups is guaranteed. Additional benefits include; monthly analysis, user-friendly reports allowing at-a-glance performance assessment, ability to register up to five instruments per programme and cost savings via our unrivalled consolidation.
Tackling Worldwide Drugs of Abuse
Throughout November, we’ve been highlighting how the Randox clinical teams – Randox Rx series, Randox Reagents and Randox QC – are aiding the fight against drugs of abuse.
Drugs of Abuse are a growing problem worldwide and represent a significant burden to healthcare systems as well as creating problems in an individual’s lifestyle. It has been estimated by the WHO (World Health Organisation) that 31 million people globally suffer from drug use disorders and 3.3 million deaths each year are linked to the abuse of both drugs and alcohol.
The abuse of drugs is one of the most pressing issues in the United States of America. Drug abuse not only affects the individual, but also can have far-reaching consequences that affect family, employment, personal health, health care systems, local communities, and society as a whole.
- Misuse of illicit drugs affects society through secondary costs incurred such as crime, reduced productivity at work, and health care expenses.
- Substance abuse costs the US health care system about $11 billion, with overall costs reaching $193 billion.
- Substance abuse and addiction also affects other areas of life and can cause broken families, destroyed careers, death due to negligence or accident, domestic violence, physical abuse and child abuse.
- Drug abuse and addiction changes the chemistry of your brain. The longer you use your drug of choice, the more damage is caused and it becomes more difficult to return to ‘normal’ during drug rehabilitation.
- In 2013, 22.7 million Americans needed treatment for a substance use disorder – almost 9% of the population over the age of 12. Only about 2.5 million received treatment as a specialist facility with 20% of admissions for opiate addication treatment and 17% for the treatment of marijuana abuse.
To find out more about how Randox is helping in the fight against Drugs of Abuse, please visit https://www.randox.com/drugs-of-abuse/ or for more information about Randox RX, Randox Reagents or Randox QC, please email marketing@randox.com.
World Diabetes Day: The Biggest Burden on the NHS
Diabetes
Approximately 400,000 people in the UK are living with type 1 diabetes, with over 29,000 being children and young people [1]. Type 1 diabetes affects 96% of all children with diabetes in England and Wales, with incidences increasing by approximately 4% each year.
Globally, the UK has the fifth highest rate of type 1 diabetes diagnosis in children (aged up to 14) with 85% of these children having no family history of the condition. Whilst the condition isn’t fatal and can be managed, it cannot be cured. Type 1 diabetes increases the risk of developing other health problems such as heart disease, stroke, foot and circulation problems, sight problems including blindness, nerve damage and kidney problems. However, many of these related conditions are preventable and it is recommended to stabilise blood sugar levels, attend diabetes appointments regularly and complete a diabetes course to educate patients and family members and prevent the risk of further help complications[2].
Diabetes in children
Children under five are at the highest risk of developing diabetic ketoacidosis due to a late diagnosis and it is also thought to be due to of lack of public knowledge of the signs and symptoms attributed to type 1 diabetes. Such symptoms include:
- Frequent urination as the kidneys are trying to expel excess sugar in the blood, resulting in dehydration which leads to extreme thirst.
- Increased hunger or unexpected weight loss because the body is unable to attain enough energy from food
- Slow healing cuts as high blood sugar levels can affect blood flow which can cause nerve damage.
- Fatigue as the body is unable to convert sugar into energy
- Irritable behaviour combined with other symptoms can be a means of concern
Diabetes and the NHS
Diabetes costs the NHS approximately £9.8 billion per year, an estimate of 10% of total expenditures. Hospital admissions of children and young people with diabetes presents a considerable burden on themselves, their families and the NHS. It is estimated that approximately 80% of these cases are potentially avoidable.
A report produced by the National Paediatric Diabetes Audit found that although the numbers of admissions didn’t significantly differ year to year, it highlighted differences in terms of socio-economic risk factors:
- Living in a deprived area increases the risk of hospital admissions which can be attributed to lack of education in the community about diabetic symptoms and the management of diabetes.
- Children below 5 years of age have a 35% increased risk of hospitalisation compared to those aged 5-9
- Females have a 33% increased risk of developing type 1 diabetes compared to males.
- Children with poor diabetes control have a twelve-fold increased risk of hospital admission
- Insulin pump users have a 27% increased risk of hospital admission compared to those who use insulin injections.
Figure A. Number of preventable paediatric diabetes admissions [3]
Prevention
There are campaigns in place to aid in the early diagnosis of type 1 diabetes which mainly focus on raising awareness of the signs and symptoms of diabetes. On this World Diabetes Day, it is important to know that it is not just simply the responsibility of the diabetic patient to prevent admission but the main responsibility lies with the diabetic teams that inform the families with children who are diagnosed with type 1 diabetes.
Paediatric diabetes teams should ensure that the families and the children receive structured education for self-management when diagnosed and throughout the illness. In doing so, the diabetic teams should implement blood ketone testing from diagnosis and utilise the nationally agreed hypoglycaemia management guidelines. It is also important that diabetic teams are fully aware of the patient characteristics associated with a greater risk of admission and that they use this knowledge to develop anti-admission strategies specifically tailored to the needs of each individual group.
Primary care practitioners should seek access to a specialist diabetic team who they can refer to when deciding if a patient requires admission to hospital. Furthermore, they should access blood glucose and ketone testing to identify patients at risk of diabetic ketoacidosis that require hospital admission.
How Randox can Help
Randox offer a range of assays to diagnosis and monitor diabetes and to monitor associated complications. Some of these tests are unique to Randox, including:
Fructosamine
The Randox fructosamine assay employs the enzymatic method which offers improved specificity and reliability compared to conventional NBT-based methods. The Randox enzymatic method does not suffer from non-specific interferences unlike other commercially available fructosamine assays.
D-3-Hydroxybutyrate (Ranbut)
The Randox D-3-Hydroxybutyrate (Ranbut) assay detects the most abundant and sensitive ketone in the body, D-3-Hydroxybutyrate. The Randox Ranbut assay is used for the diagnosis of ketosis, more specifically diabetic ketoacidosis. Other commercially available tests, such as the nitroprusside method, are less sensitive as they only detect acetone and acetoacetate, not D-3-Hydroxybutyrate.
Adiponectin
The Randox adiponectin assay is a biomarker in diabetes testing as adiponectin is a protein hormone responsible for regulating the metabolism of lipids and glucose and influences the body’s response to insulin. Adiponectin levels inversely correlates with abdominal visceral fat levels.
Want to know more?
Contact us or visit our Diabetes panel page to learn more.
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References
[1] National Paediatric Diabetes Audit and Royal College of Paediatrics and Child Health, National Paediatric Diabetes Audit Report 2012-15: Part 2, 2017
[2] NHS, “Avoiding Complications” – Type 1 Diabetes, Available at: https://www.nhs.uk/conditions/type-1-diabetes/avoiding-complications/ [Accessed on 24th October 2018].
[3] “Potentially Preventable Pediatric Hospital Inpatient Stays for Asthma and Diabetes, 2003-2012”, www.hcup-us.ahrq.gov, 2015. [Online] Available: https://www.hcup-us.ahrq.gov/reports/statbriefs/sb192-Pediatric-Preventable-Hospitalizations-Asthma-Diabetes.jsp [Accessed 08-Nov-18]
