Could H-FABP Have Potential Benefits in Diagnostics Beyond Cardiac Health Problems?
To date, the most traditional diagnostic test for renal impairment is creatinine. However, although most commonly used, problems can arise when implementing this test as a number of factors are not considered. On this World Kidney Day, Randox will explore the potential utility of H-FABP as a clinical diagnostic marker for cardiac surgery-associated acute kidney injury.
Acute Kidney Injury (AKI) is defined as an acute decline in renal function that can lead to structural changes. It involves a sudden drop in kidney function that usually arises due to a complication of another serious illness such as impaired renal perfusion, exposure to nephrotoxins, outflow obstruction or intrinsic renal disease. As a result, a patient can experience effects such as impaired clearance and regulation of homeostasis, altered acid/base and electrolyte regulation and impaired volume regulation.1
The mortality rate associated with AKI varies depending on severity, patient related factors and setting including whether the patient is in intensive care (ICU) or not.2 In the UK, AKI has been found to affect 1 in 5 people admitted to hospital as an emergency and has been found to be deadlier than a heart attack, contributing to around 100,000 deaths each year. Conversely, in the US, age-standardized rates of acute kidney injury hospitalisations increased by 139% among adults with diagnosed diabetes and by 230% among those without diabetes.3, 4
The rising incidence of AKI comes at price. Patients tend to survive ICU but will be discharged with various degrees of chronic kidney disease (CKD), placing an increasing strain on the health care system. At present, the cost to the NHS is estimated to be between £434 and £620 million, which is more than the costs associated with breast cancer, or lung and skin cancer combined. However, this increased cost and strain could be unnecessary, as research has shown that 30% of the reported 100,000 deaths in the UK could have been prevented with the right care and treatment.3,4
These unfavourable statistics are the result of late detection of AKI, as to date, a superior method of detection has not been found.
Cardiac surgery-associated acute kidney injury (CSA-AKI)
CSA-AKI is a well-recognised postoperative complication of cardiac surgery and is the second most common cause of AKI in the intensive care unit, occurring in up to 30% of patients.5,6 Of these patients, an estimated 1% will require dialysis and the majority will remain dependent on dialysis leading to an increase in mortality. Certain patient groups are more susceptible to CSA-AKI and vulnerability can depend on age, sex, pre-existing cardiac dysfunction, pre-existing CKD, previous cardiac surgery or comorbidity.7
The pathogenesis of AKI involves multiple pathways including hemodynamic, inflammatory and nephrotoxic factors that overlap leading to kidney injury.6 Figure 1 illustrates the pathophysiology of AKI following cardiac surgery. It shows that there are multiple physiological processes that are associated with the development of AKI as a result of cardiac surgery.8
Figure 1 Illustrates the pathophysiology of AKI following cardiac surgery and the various mechanisms that contribute.8
What is H-FABP?
Fatty acid-binding proteins (FABPs) are small cytoplasmic proteins that are abundantly expressed in tissues with an active fatty acid metabolism, with their primary function being the facilitation of intracellular long-chain fatty acid transport.9 Elevated FABP serum concentrations are related to a number of common comorbidities including heart failure, CKD, diabetes mellitus and metabolic syndrome, which represent important risk factors for postoperative AKI.10
H-FABP is most commonly associated with being a marker for acute coronary syndrome (ACS) as its concentrations peak at approximately 6-8 hours after symptom onset, making it easier to detect. Recently studies have highlighted H-FABP as a potential biomarker for the detection of AKI after cardiac surgery. This potential would mean earlier diagnosis of patients, reducing the mortality rate and costs to the health service.
Potential Mechanism for the release of H-FABP in AKI
There are a number of hypotheses regarding the release of H-FABP, with myocardial injury being considered the major reason for an increased level. The mechanisms involved in this increase have been found to differ depending on the severity of a patients ACS situation including whether they are in ICU.11
One possible explanation for the release of H-FABP is the effects of ischemic stress. Ischemic stress induced by non-cardiogenic shock is a type of mechanical stretching which can lead to the leakage of small amounts of macromolecules. This process would lead to the release of H-FABP into the blood. In non-cardiac patients, minor myocardial injury alone may not adequately explain this observed increase. Other factors such as a reduction in the amount of skeletal muscle tissue, lipid disorders, release of free radicals and an increase in free acids produced by the catabolism of glycogen could also contribute to a rise in H-FABP levels.11
One final process that could lead to increased H-FABP is the damage of vital organ functions which occurs in almost all non-surgical intensive care patients. The degree of leakage of H-FABP may vary depending on the severity of a patient’s condition and whether they have suffered from multiple organ failure or vital organ damage. AKI is a component of multiple organ failure suggesting that serum H-FABP levels may increase in AKI patients as a result. Also, serum H-FABP is excreted by renal tubular cells and patients with an acutely diminished renal function are unable to clear large amounts of H-FABP resulting in increasing levels. These potential mechanisms of H-FABP and its release during AKI provide further confirmation that the measurement of serum H-FABP is an effective biomarker in patients with AKI.11
Comparison of H-FABP Measurement Against Traditional Acute Kidney Disease Measurement Tools
For years, no standard method for definition or diagnosis was in place for AKI. The RIFLE classification was introduced in 2004, which defined and staged renal failure over seven days into five classes of increasing severity including; risk, injury, failure, loss and end-stage kidney disease.
The RIFLE criteria were then revised by the Acute Kidney Injury Network (AKIN) and introduced four main changes including replacing the period of seven days for serum creatinine (SCr) with forty eight hours and implementing SCr changes as low as 0.3 mg/dL as the lowest measure considered as AKI. However, despite these changes the Kidney Disease Improving Global Outcome (KDIGO) proposed that AKI is defined when any of the three criteria are met including increase in SCr by 50% in seven days, increase in SCr > 0.3 mg/dL or oliguria.7
However, despite these advances, identification and management of AKI is still difficult for two main reasons. The change of SCr does not occur until two to three days after the initial insult. Also, serum creatinine can rise for a variety of reasons such as tubular injury, hemodynamic alterations or cardio-renal interactions.
The utility of SCr as biomarker for CSA- AKI is questionable as changes occur 48 hours to seven days after the original insult.5 The delays in diagnosis of CSA-AKI may have detrimental effects as prolonging the diagnosis period may result in the disease already being well established.12
Also, a main issue concerning the AKI criteria established is its relevance to the perioperative period. Many surgical patients arrive in hospital without preoperative SCr concentrations being measured, potentially leading to over-diagnosis of AKI. However, when patients do arrive with a preoperative SCr concentration, the opposite can occur and immediate postoperative period SCr concentrations can be lower than baseline as a result of haemodilution. A comparison of the postoperative and preoperative values can lead to under-diagnosis of AKI and consequently delayed treatment.12
The research conducted has illustrated that SCr is not the most appropriate biomarker for diagnosis of AKI. Studies have demonstrated that H-FABP has more clinical utility and is released less than thirty minutes after myocardial injury and renally excreted within 24 hours, showing that as a biomarker it responds faster than creatinine.12
How Randox can Help
The Randox H-FABP test tests utilises an immunoturbidimetric method, offers a wide measuring range and is available liquid ready-to-use for convenience and ease of use.
Want to know more?
Contact us or visit the Randox H-FABP Site
- National Kidney Foundation. Acute Kidney Injury (AKI). National Kidney Foundation. [Online] National Kidney Foundation. [Cited: February 3, 2019.] https://www.kidney.org/atoz/content/AcuteKidneyInjury.
- Biomarkers for the prediction of acute kidney injury: a narrative review on current status and future challenges. Geus, de, MG, Betjes and J , Bakker. 2, s.l. : NCBI, 2012, Vol. 5.
- Kidney Care UK. A range of useful facts and stats about kidneys. Kidney Care UK. [Online] Kidney Care UK. [Cited: February 15, 2019.] https://www.kidneycareuk.org/news-and-campaigns/facts-and-stats/.
- Centers for Disease Control and Prevention. Trends in Hospitalizations for Acute Kidney Injury — United States, 2000–2014. Centers for Disease Control and Prevention. [Online] Centers for Disease Control and Prevention, March 16, 2018. [Cited: February 22, 2019.] https://www.cdc.gov/mmwr/volumes/67/wr/mm6710a2.htm.
- Cardiac Surgery-Associated Acute Kidney Injury. Mao, h, et al. s.l. : Karger, 2013, Vol. 3.
- Acute Kidney Injury Associated with Cardiac Surgery. Rosner, Mitchell and Okusa, Mark. 1, s.l. : Clinical Journal of American Society of Nephrology, 2016, Vol. 1.
- Cardiac surgery-associated acute kidney injury. Loubon, Christian, et al. 4, s.l. : NCBI, 2016, Vol. 19.
- Acute kidney injury following cardiac surgery: current understanding and future directions. O’Neal, Jason, Shaw, Andrew and Billings, Frederic. s.l. : NCBI, 2016, Vol. 20.
- Heart-type fatty acid-binding protein predicts long-term mortality after acute coronary syndrome and identifieshigh-risk patients across the range of troponin values. Kilcullen, N, et al. 20, s.l. : Epub, 2012, Vol. 50.
- Preoperative serum h-FABP concentration is associated with postoperative incidence of acute kidney injury in patients undergoing cardiac surgery. Oezkur, Mehmet, et al. 117, s.l. : BMC Cardiovascular Disorders, 2014, Vol. 14.
- The serum heart-type fatty acid-binding protein (HFABP) levels can be used to detect the presence of acute kidney injury on admission in patients admitted to the non-surgical intensive care unit. Shirakabe, A, et al. 1, s.l. : NCBI, 2016, Vol. 16.
- Perioperative acute kidney injury. Goren, O and Matot, I. 2, s.l. : British Journal of Anaesthesia, 2015, Vol. 115.
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 
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
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:
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.
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.
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.
Want to know more?
Contact us or download our Cardiology and Lipid Testing brochure to learn more.
Lipid Panel Page
 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
 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/
 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.
 NORD. Hyperlipoproteinemia Type III. NORD. [Online] 2019. [Cited: February 21, 2019.] https://rarediseases.org/rare-diseases/hyperlipoproteinemia-type-iii/
 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
 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
 Medline Plus. Familial Dysbetalipoproteinemia. Medline Plus. [Online] May 16, 2018. [Cited: February 21, 2019.] https://medlineplus.gov/ency/article/000402.htm.
 Dysbetalipoproteinemia: Two cases report and a diagnostic algorithm. Kei, Anastazia, et al. 4, s.l. : World Journal of Clinical Cases, 2015, Vol. 3.
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.
Want to know more?
Contact us or visit our featured reagent page to learn more.
- 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.
Approximately 400,000 people in the UK are living with type 1 diabetes, with over 29,000 being children and young people . 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.
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 
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:
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.
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.
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.
 National Paediatric Diabetes Audit and Royal College of Paediatrics and Child Health, National Paediatric Diabetes Audit Report 2012-15: Part 2, 2017
 NHS, “Avoiding Complications” – Type 1 Diabetes, Available at: https://www.nhs.uk/conditions/type-1-diabetes/avoiding-complications/ [Accessed on 24th October 2018].
 “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]
On a global scale, 1.62 billion people are affected by anaemia which is equivalent to 24.8% of the population ₁. According to a review carried out by WHO of various national surveys, anaemia affects approximately 42% of pregnant women worldwide and it is also estimated that at least 50% of all anaemia cases are due to iron deficiency.
Anaemia caused by iron deficiency is usually expected during pregnancy. This is due to several reasons: the increased demand for iron by a pregnant woman’s body from increased total blood cell volume, requirements of the foetus and placenta as well as mass blood loss during labour₂. Although iron cost is unbalanced by the lack of loss of menstrual blood during pregnancy, the net cost is still high enough that iron recommendations are higher than in non-pregnant women. Also, iron is critical during pregnancy considering its involvement in foetal growth: 600-800mg of iron is required during pregnancy with around 300mg needed just for the foetus, a minimum of 25mg for the placenta and almost 500mg due to the increase in volume of red blood cells. ₃
Iron deficiency is the most common micronutrient deficiency in pregnant women leading to iron deficiency anaemia if left untreated. However, iron deficiency can be difficult to measure in some populations due to the lack of availability of field-specific biomarkers. For example, anaemia can affect up to 56% of pregnant women in developing countries, which suggests a high prevalence of iron deficiency anaemia: around 25%. In settings with endemic malaria, such as certain countries in Africa, the number of pregnant women with anaemia is much higher: around 65%.
There are various factors that may increase the risks of iron deficiency anaemia. For example, a diet influenced by religious beliefs can cause a lack of iron in the diet, such as vegetarianism which is common in countries such as India where religious beliefs dictate this. Iron levels can also be affected by consumption of nutrients which inhibit proper absorption of iron, such as calcium or ones that promote iron absorption, such as vitamin C. Other circumstantial risks include infections, multiple pregnancies and adolescent pregnancy while socioeconomic factors and access to healthcare mean some women won’t have access to anaemia control programs, iron supplements or even access to information about iron deficiency anaemia during pregnancy.
To prevent iron deficiency, international guidelines state that iron supplementation to manage iron deficiency is recommended during pregnancy. ₄ However, this is not always available, especially in developing countries.
Iron deficiency anaemia during pregnancy can cause several complications for the mother including:
- Increased fatigue
- Short-term memory loss
- Decreased attention span
- Increased pressure on the cardiovascular system due to insufficient haemoglobin and blood oxygen levels
- Lower resistance to infections
- Reduced tolerance to significant blood loss and surgical implications during labour.
As expected, neonates with mothers who suffered from iron deficiency anaemia during pregnancy will also be confronted with risks and, even if iron deficiency is only mild to moderate, can result in a premature birth, complications with foetal brain development, low birth weight and even foetal death. Additionally, it has been proven that cognitive and behavioural abnormalities can be seen in children for up to ten years after iron insufficiency in the womb.
Randox Reagents offer a Soluble Transferrin Receptor assay to expand upon our current iron testing offering.
In iron deficiency anaemia, soluble transferrin receptor levels are significantly increased, however, remain normal in acute phase conditions including: chronic diseases and inflammation. As such, sTfR measurements are useful in the differential diagnosis of anaemia: anaemia of chronic disease or iron deficiency anaemia.
In iron deficiency anaemia, increased sTfR levels have also been observed in haemolytic anaemia, sickle cell anaemia and B12 deficiency.
The benefits of the Randox Soluble Transferrin Receptor (sTfR) Reagent include:
- Latex enhanced immunoturbidimetric method facilitating testing on biochemistry analysers and eliminating the need for dedicated equipment.
- Liquid ready-to-use reagents for convenience and ease-of-use
- Stable to expiry date when stored at +2 to +8 °C
- Excellent measuring range of 0.5 – 11.77mg/L, comfortably detecting levels outside of the normal health range of 0.65 – 1.88mg/L
- Excellent correlation coefficient of r=0.977 when compared against other commercially available methods
- Applications available detailing instrument-specific settings for a wide range of clinical chemistry analysers
Find out more at: https://www.randox.com/stfr/
- de Benoist B et al., eds.Worldwide prevalence of anaemia 1993-2005. WHO Global Database on Anaemia Geneva, World Health Organization, 2008.
- Harvey et al, Assessment of Iron Deficiency and Anemia in Pregnant Women: An Observational French Study, Women’s Health, Vol 12 Issue 1, 2016
- Burke et al, Identification, Prevention and Treatment of Iron Deficiency during the First 1000 Days, Nutrients, Vol 6 Issue 10, 2014
- Guideline: Daily Iron and Folic Acid Supplementation in Pregnant Women. World Health Organization; Geneva, Switzerland: 2012
Diet trends have continued to evolve throughout the years with a strong influence from celebrities. Beginning in the 1930s the grapefruit diet aka the “Hollywood diet” started which encouraged eating a grapefruit with every meal. More recently an increasing amount of extreme diet trends have emerged. In 2004, Beyoncé started the master cleanse involving a concoction of hot water, lemon juice, maple syrup and cayenne pepper and even crazier was Reese Witherspoon’s “baby food diet”. The newest trend to materialise is the keto diet favoured by celebrities including Halle Berry and the Kardashians. However, the results for long term weight loss and the safety of the diet is still questioned.
What is the ketogenic diet?
The ketogenic diet is a low carb diet which involves drastically reducing carbohydrate intake and replacing it with fat. Initially, the purpose of the ketogenic diet was not to aid weight loss but was prescribed to aid in the treatment of tough-to-control epileptic seizures that were unresponsive to drugs. In the 1920s the diet was found to significantly reduce the frequency of seizures in children. However, the benefits for weight loss have also been realised as the carbohydrate reduction kicks the body into a natural fat burning state called ketosis. By starving the body of carbohydrates and sugars, the first fuel the body burns, the body looks for another source of fuel to retrieve its energy. The body becomes efficient at burning fat for energy whilst also turning fat into ketones in the liver which can supply the brain with energy.
The metabolism of fatty acids in the liver results in the production of ketone bodies. These comprise of three chemicals consisting of acetone (2%), acetoacetate (20%) and D-3-Hydroxybutyrate (78%) and this production is called ketogenesis. The ketone bodies are produced by the chemical acetyl-CoA predominantly in the mitochondrial matrix of liver cells. This process is necessary in small amounts particularly when carbohydrates are scarce, and glucose is not available as a fuel source.
The ketone bodies are water soluble allowing for the transportation across the inner mitochondrial membrane as well as across the blood brain barrier and cell membranes. This allows them to source the brain, heart and muscle with fuel. Interestingly, during starvation they are the major energy source for the brain, providing up to 75%.
The excess production of ketones can accumulate in the body creating a state of ketosis. This stage, although abnormal, is not considered harmful, which is why it is being promoted as a diet craze. However, due to the acidic nature of the ketone bodies, particularly D-3-Hydroxybutyrate, larger amounts of ketone bodies can cause the pH levels in the body to drop to dangerously acidic levels creating a state of ketoacidosis.
The benefits of the keto diet have been well advertised and received a lot of celebrity support. With powerful celebrities such as Halle berry ‘swearing by it’ as it allows her to manage her diabetes, it is easy to see why so many are keen to try it. However, with little to no information about the long-term effects, should we be finding out more before trying it ourselves?
In 2006, a study was conducted reviewing the influence of a low-carbohydrate diet can have on ketoacidosis. In this study the patient who had no history of diabetes was placed on a strict low carbohydrate diet for four years. Although the patient showed a significant decrease in weight on the diet, they also experienced four episodes of ketoacidosis. Each time an episode occurred the patient was administered intravenous fluids and insulin which lead to their recovery, however each time they returned to the diet it wasn’t long before another ketoacidosis episode occurred. When the patient was placed on a diet containing normal amounts of carbohydrates their glucose levels returned to normal, preventing a ketoacidosis episode from occurring again. The more ketones in the blood, the more ill a person with ketoacidosis will become. Left untreated ketoacidosis can cause potentially fatal complications such as severe dehydration, coma and swelling of the brain.
Randox D-3-Hydroxybutyrate (Ranbut) Reagent
Randox Reagents offer a D-3-Hydrobutyrate assay designed to measure the major ketone lvels in the body, D-3-Hydroxybutyrate, allowing for an efficient diagnosis to be implemented. The superior methodology provides more accurate, reliable and specific results compared to the traditional dipstick method of ketone body measurement.
The benefits of the Randox D-3-Hydroxybutyrate (Ranbut) assay include:
- Excellent precision of less than 3.5% CV
- Exceptional correlation coefficient of r=0.9954 when compared against other commercially available methods.
- A wide measuring range of 0.100 – 5.75mmol/l, comfortably detecting levels outside of the healthy range, 0.4 – 0.5mmol/l.
- Enzymatic method for accurate and reliable results
- Reconstituted stability of 7 days when stored between +2 to +8⁰C
- Ketoacidosis during a low-carbohydrate diet. Shah, Panjak and Isley, William. s.l. : The new england journal of medicine, 2006, Vol. 354.
Cardiovascular disease (CVD) is the number one cause of death globally and more people die annually from CVD than any other disease state. On World Heart Day 2018, Randox Reagents are committed to developing niche and superior performance assays for the early detection of CVD risk with the hope to change this statistic and improve the heart health of millions worldwide.
There are a number of influencing factors that can lead to a patient experiencing a cardiovascular event. The risk factors for this multifactorial disease include: genetic predisposition, age, gender, smoking, hypertension, stress, dietary habits and physical inactivity. Little evidence exists explaining the mechanism of the Apolipoproteins in the body and their contribution to the causes of some of these cardiac diseases.
Apolipoprotein E (Apo E) is a lipid transport and signalling protein found in the blood which is synthesized mostly by the liver. Apo E has been found to have many roles in the body including the promotion of antiatherogenic properties. Essentially the main function of Apo E is to act as a ligand to the LDL receptor. This relationship plays a critical role in metabolism by promoting cellular uptake of lipoproteins. Through this process Apo E acts as a major component of overall plasma cholesterol homeostasis which facilitates the hepatic uptake of lipoproteins by binding to their receptors. It works to stabilise the equilibrium of cholesterol in the blood by transporting the cholesterol between cells preventing platelet aggregation. Apo E deficiency can influence the plasma concentration and metabolic destination of LDL creating an increased risk of CVD.
Apolipoprotein C-III is another apolipoprotein found in the circulatory system. Its metabolic actions have been found to be actively different to ApoE. The Apo C-III has been found to prevent binding of VLDL cellular receptors resulting in the conversion of VLDL to LDL rather than promoting the clearance of the circulatory system. In addition, it specifically and directly encourages proatherogenic changes in monocytes and endothelial cells. Research has found that the plasma concentration of LDL with Apo C-III strongly predicts the incidence of recurrent cardiovascular events.
Working together to lower CVD Risk
The conflicting roles of Apo E and Apo C-III in the circulatory system has created interest amongst researchers and has raised the question ‘Could the ApoE content of LDL Cholesterol with Apo C-III reduce the proatherogenic nature of Apo C-III reducing a patient’s risk of a CVD event?’.
In fact, studies have now found that the presence of ApoE is associated with lower atherogenicity of LDL Cholesterol containing Apo C-III. The abundance ApoE relative to the abundance of LDL Cholesterol with Apo C-III is a protective factor against coronary heart disease. This relationship is further supported by the antagonistic relationship between the two apolipoproteins. The idea that Apo E may be able to effectively protect against the effects of the combination of LDL Cholesterol with Apo C-III is important to consider due to their strong links with CVD.
The Randox Apolipoprotein E and Apolipoprotein C-III reagent allows for prompt and accurate diagnosis of Apolipoprotein levels, an influencing factor in cardiovascular disease.
The Randox Apolipoprotein E reagent
The benefits of the Randox Apo E assay includ:
- Excellent working reagent stability when stored at +2 to +8 ̊C
- A wide measuring range of 1.04 -12.3 mg/dl enabling the comfortable detection of levels outside of the health range, 2.7-4.5 mg/dl
- Liquid ready-to-use reagent for convenience and ease-of-use
- Immunoturbidimetric method
The Randox Apolipoprotein C-III reagent
The key benefits of the Randox C-III assay include:
- Liquid ready-to-use reagent for convenience and ease-of-use
- Excellent Linearity of 21.7 mg/dl. The approximate normal upper limit for Apo CIII is 9.5 mg/dl therefore the Randox assay will comfortably detect elevated, potentially harmful levels of Apo C-III
- Limited interference from Bilirubin, Haemoglobin, Intralipid and Triglycerides for truly accurate results
- Applications are available detailing instrument-specific settings for a wide range of clinical chemistry analyzers
- Immunoturbidimetric method
- Apolipoprotein E in VLDL and LDL with Apolipoprotein C-III is Associated with a Lower Risk of Coronary Heart Disease. Mendivil, Carlos, et al. s.l. : Journal of the American Heart Association , 2013.
Lactic acid is an organic compound which produces the conjugate base lactate through a dissociation reaction. Due to it being a chiral compound, two optical isomers of lactate exist; D-Lactate and L-Lactate. The lactate dehydrogenase (LDH) enzyme can produce and metabolise both isomer forms to pyruvate, however due to the isomer-specific nature of LDH different forms of the enzyme are required. D-Lactate requires a D-LDH form whereas L-Lactate requires L-LDH. As a result of this requirement, combined with the fact that mammalian cells only contain L-LDH, the lactate produced in humans is almost exclusively L-Lactate.
One of the roles of L-Lactate is its involvement in the Cori Cycle, a metabolic pathway involved in the production of glucose. The cycle involves the rotatory transportation of lactate and glucose from the liver and the muscle. Lactate is produced in the muscle through glycolysis which is then transported to the liver through the blood stream. In the liver, the lactate is oxidised to pyruvate and then converted to glucose by gluconeogenesis, which is then transported back to the muscle for the process to start again. 1500 mmol of lactate is produced daily by the body and is cleared at a constant rate via the liver.
Problems can arise if the liver fails to regulate the lactate produced. Hyperlactamia is the name given to elevated levels of lactate in the body, as a result of the rate of production exceeding the rate of disposal. This is due to a lack of oxygen that reduces blood flow to the tissues. If levels continue to rise a patient is at risk of lactic acidosis.
The liver is an important tissue in the regulation of lactate, it is therefore no surprise that liver damage can prevent this process resulting in a further diagnosis of lactic acidosis. A healthy liver is a vital part of lactate regulation as it acts as the main consumer of lactate and contributes to 30-40% of lactate metabolism. Potential victims are patients who suffer with cirrhosis, a complication of liver disease, which is commonly caused by alcohol abuse and viral Hepatitis B and C.
Patients with liver cirrhosis have a higher risk of increased lactate levels. Increased levels of the lactate ions disturbs the acid-base equilibrium, causing a tilt towards lactic acidosis. The mortality rate of patients who develop lactic acidosis is high, prompt recognition and treatment of the underlying cause remain the only realistic hope for improving survival.
The Randox L-Lactate reagent allows for a prompt and accurate diagnosis of lactic acidosis.
Randox L-Lactate Reagent
The Randox L-Lactate key benefits include:
- Excellent working reagent stability of two weeks when stored at + 15 – +25°C
- Exceptional correlation of r = 0.99 when compared against other commercially available methods
- A wide measuring range of 0.100 – 19.7 mmol/l and so is capable of detecting abnormal levels in a sample
- Colorimetric method
- Lyophilised reagents for enhanced stability
The aim of Biomedical Science Day is to raise the public’s awareness of the importance of biomedical science and the vital role it plays in the world. Randox are dedicated to improving healthcare worldwide through placing a major focus on research and development. The Randox scientists work in pioneering research into a range of common illnesses such as cancer, cardiovascular disease and Alzheimer’s disease.
A recent blog from Doris-Ann Williams, the Chief Executive at BIVDA, explains how “increased funding is not enough to sustain the NHS” and how “we need to make better use of in vitro diagnostics to ensure a successful future”.
The National Health Service (NHS) is a publicly funded, primarily taxation, national healthcare system in the United Kingdom. It was first set-up on July 5th, 1948 by Aneurin Bevan as he believed that everyone, regardless of wealth, should have access to good healthcare. Whilst the NHS is an extremely important aspect of healthcare in the UK, in vitro diagnostics are the heart and soul of the healthcare system as healthcare professionals not only rely on blood tests to diagnose and treat patients, but also to rule out the different contributing causes to a disease state. In vitro diagnostics also plays a key role in monitoring chronic disease states. In vitro diagnostics can also aid in reducing hospital stays, reduce misdiagnosis and support patients in looking after their own health and to deliver personalised treatment plans.
The Randox scientists have developed several niche assays to improve patient diagnosis, monitor treatment and eliminate misdiagnosis.
Adiponectin is a protein hormone secreted by adipocytes with anti-inflammatory and insulin-sensitising properties. It plays an important role in a number of metabolic processes including glucose regulation and fatty acid oxidation. Adiponectin levels are inversely correlated with abdominal visceral fat which have proven to be a strong predictor of several pathologies, including: metabolic syndrome, type 2 diabetes mellitus (T2DM), cancers and cardiovascular disease (CVD). For more information on the importance of testing Adiponectin levels, check out our Adiponectin Whitepaper.
Cystatin C is an early risk marker for renal impairment. The most commonly run test for renal impairment is Creatinine. Creatinine measurements have proven to be inadequate as certain factors must be taken into consideration, including age, gender, ethnicity etc. The National Institute for Health and Care Excellence (NICE) have updated their guidelines, which now recommends Cystatin C as a more superior test for renal impairment due to its higher specificity for significant disease outcomes than those based on Creatinine. For more information on the importance of testing Cystatin C levels, check out our Cystatin C Whitepaper.
Small-dense LDL Cholesterol (sdLDL-C)
LDL Cholesterol (LDL-C) consists of two parts: the large and buoyant LDL Cholesterol and the small and dense LDL Cholesterol. Whilst all LDL-C transports triglycerides and cholesterol to bodily tissues, their atherogensis varies according to their size. As sdLDL-C is small and dense, they can more readily permeate the arterial wall and are more susceptible to oxidation. Research indicates that individuals with a predominance of sdLDL-C have a 3-fold increased risk of myocardial infarction. It has been noted that sdLDL-C carries less Cholesterol than large LDL, therefore a patient with predominately sdLDL-C particle may require nearly 70% more sdLDL-C particles to carry the same amount of cholesterol as the patient with predominately LDL-C particles. For more information on the importance of testing sdLDL-C levels, check out our sdLDL-C Whitepaper.
These three niche in vitro diagnostics tests developed by Randox scientists can aid in reducing NHS costs due to their higher performance compared to the traditional tests. Randox are constantly striving to improve healthcare worldwide.
For more information on the extensive range of Randox third-party in vitro diagnostic reagents, visit: https://www.randox.com/diagnostic-reagents/ or contact firstname.lastname@example.org.
Homocysteine is a thio-containing amino acid produced by the intracellular demethylation of methionine. Elevated levels of homocysteine (hyperhomocysteinemia) is more common in women than in men and is associated with a wide array of illnesses. It has also been proven to cause several problems in women including: cardiovascular disease (CVD), colon cancer, pregnancy complications, and birth defects.
Elevated levels of circulating homocysteine correlates with an increased risk of vascular occlusion (blockage of a blood vessel). Hyperhomocysteinemia can cause inflammation of the endothelium (thin layer of cells linking the interior blood vessels). Failure to lower homocysteine levels can cause further inflammation of the arteries, veins, and capillaries causing atherosclerosis. Consequently, blood and oxygen supply to tissues is reduced, increasing the risk of cardiovascular disease. Elevated levels correlates with higher diastolic and systolic blood pressure, hypertension. However, this correlation is stronger in women than in men. Women with elevated levels of homocysteine have a 3-fold increased risk of CVD, whereas men have a 2-fold increased risk.
Women with hyperhomocysteinemia have an increased risk of colorectal cancer than women with lower levels. Women who present with the highest levels of homocysteine have more than a 70% increased colorectal cancer risk. A correlation between reduced levels of folate and increased levels of homocysteine have been found in women with colorectal adenoma. It is recommended that women with hyperhomocysteinemia and reduced levels of folate should increase their intake of fruit and vegetables to reduce their levels of homocysteine and increase their levels of folate.
Pregnancy Complications and Birth Defects
Homocysteine levels should decline during pregnancy, however, in some cases, levels increase. Hyperhomocysteinemia is associated with foetal neural tube defects which causes various conditions, characterised by placental vasculopathy, including pre-eclampsia, abruption, and recurrent pregnancy loss. It has been identified that folate supplementation can half the risk of foetal neural tube defects. One study found that hyperhomocysteinemia was associated with a 2-fold to 3-fold increased risk for pregnancy-induced hypertension, abrupyio placentae, and intrauterine growth restriction.
Randox Homocysteine Reagent
The Randox Homocysteine assay offers a few unique features:
- Limited interference from Bilirubin, Haemoglobin, Triglycerides, and Intralipid, producing more accurate and precise results.
- Two-reagent format for convenience and ease of use
- Calibrator provided with kit, simplifying the ordering process
Other features include:
- Liquid ready-to-use reagents – for optimum user experience
- Excellent linearity – 47. 9 μmol/L, ensuring abnormally high levels of homocysteine are detected.
- Enzymatic method
- Tri-level cardiac control available