Acute Kidney Injury and Antimicrobial Stewardship
An estimated 1 in 5 hospital admissions in the UK is associated with acute kidney injury1, providing a clear illustration of the need for novel, rapid detection methods. Our latest whitepaper looks at this common condition and the links between Acute Kidney Injury and Antimicrobial Stewardship. For more details on the things discussed in this article, you can download the full whitepaper below.
Acute Kidney Injury
Acute Kidney Injury is defined as a sudden loss of kidney function. This causes a disruption in the kidneys’ ability to filter waste out of your blood resulting in an accumulation of waste products as well as other imbalances.
The loss of kidney function is the result of a sudden reduction in glomerular filtration rate (GFR), the process through which waste is extracted from the blood and is often reversible2.
Aetiology of Acute Kidney Injury
The differential pressure existing between the glomerulus and Bowman’s is the driving mechanism for glomerular filtration2. This pressure contrast is influenced by the combined resistances of the afferent (leading to the glomerulus) and efferent (leading away from the glomerulus) vascular pathways in the kidney. Under normal kidney function, these resistances are in equilibrium, facilitating the proper functioning of the GFR. For example, an increase in efferent resistance restricts the blood flow out of the kidney, elevating pressure inside the kidney and reducing GFR, and vice versa2. However, in AKI, the decline in renal blood flow and GFR has a pathological origin. The pathophysiology of AKI can be classified as prerenal, intrinsic renal, or postrenal.
Pre-renal Acute Kidney Injury
Pre-renal AKI is caused by reduced afferent blood flow or, in other words, increased afferent resistance. While tubular and glomerular functions generally remain intact, pre-renal AKI may be caused by systemic hypoperfusion (decreased blood flow) or selective hypoperfusion to the kidney, caused by renal artery stenosis or aortic dissection3.
Intrinsic Renal Acute Kidney Injury
Renal AKI describes the conditions which affect the glomerulus or tubule, for example, acute tubular necrosis and acute interstitial nephritis. This collection of conditions is associated with vasoconstrictor expression in renal afferent pathways2.
Post-renal Acute Kidney Injury
Post-renal AKI usually results from an obstruction in the filtration system. Causes of obstruction include kidney stones, tumours, or blood clots, commonly in the bladder outlet. Obstruction affecting one side might not invariably lead to acute kidney injury, especially when the impediment develops slowly, such as with tumour growth. This is because the unaffected kidney might be able to adjust and make up for the compromised functionality3
Symptoms & Treatment
AKI often manifests with decreased urine output as its primary symptom. However, additional symptoms, when present, can encompass fatigue, nausea, vomiting, or confusion4. To achieve an accurate diagnosis, a comprehensive review of the patient’s medical history and a physical examination are essential to identify the underlying cause of the condition.
The treatment and management of AKI are contingent upon the root cause of the condition. In milder cases, measures are implemented to maintain appropriate levels of fluid, electrolytes, and blood pressure. Nutritional support may also be administered when necessary. In the most severe instances of AKI, dialysis may be warranted to compensate for the diminished kidney function5.
Creatinine serves as a valuable diagnostic tool for evaluating renal conditions, including kidney health, GFR, and muscular dystrophy. However, abnormal serum creatinine (SCr) levels only become evident when a significant portion of the renal mass is compromised. The kidneys possess an impressive capacity to adapt to reduced function, which means that a considerable loss of function or GFR is necessary to influence SCr levels. This poses a challenge when it comes to early detection of AKI6.
Novel biomarkers, KIM-1, NGAL, Clusterin, and Cystatin C, are associated with AKI2 and can be analysed through molecular testing. These new methods can provide a fast and accurate assessment of an individual’s kidney health, at a much earlier stage than SCr quantification2.
Antimicrobial Stewardship
Antimicrobial Stewardship (AMS) programs are specifically crafted to enhance the efficiency of antimicrobial utilization, curtail the emergence of Antimicrobiasl Resistance (AMR), and enhance patient outcomes7. These programs encompass a variety of approaches, such as educational initiatives, training, the establishment of guidelines and protocols, ongoing monitoring and feedback regarding antimicrobial usage, and the management of antimicrobial formularies. Through the promotion of prudent antibiotic utilization, AMS programs contribute to the safeguarding of the efficacy of currently available antimicrobial agents and the deceleration of AMR development7.
Antibiotics and Acute Kidney Injury
Various antibiotics are associated with the progression of AKI due to their nephrotoxicity which can cause severe damage to the kidneys. These antibiotics include polymyxins, aminoglycosides and the commonly used, vancomycin8.
Randox Renal Injury Detection
Using the patented Biochip Technology, the Randox Acute Kidney Injury (AKI) array, available on the Evidence Investigator, simultaneously tests for four novel biomarkers (KIM-1, NGAL, Clusterin, Cystatin C) delivering an early diagnosis and monitoring of treatment efficacy. Multiplex testing better captures reduced renal function, as each biomarker reflects different mechanisms that result in similar injury outputs, allowing for a more accurate picture of the underlying cause of AKI. Along with being able to identify AKI at a much earlier stage, this array provides an accurate and sensitive solution for the diagnosis and monitoring of AKI.
If you’d like some more information on the Randox Acute Kidney Injury Array or would like to add this technology to your laboratory, take a look at our website at https://www.randox.com/acute-kidney-injury/ or get in touch today at marketing@randox.com.
References
- NICE. How common is it? Acute Kidney Injury . Published July 2023. Accessed October 2, 2023. https://cks.nice.org.uk/topics/acute-kidney-injury/background-information/prevalence/
- Adiyanti SS, Loho T. Acute Kidney Injury (AKI) Biomarker.; 2012.
- Manzoor H, Bhatt H. Prerenal Kidney Failure.; 2023.
- NHS. Acute Kidney Injury. NHS. Published 2023. Accessed July 31, 2023. https://www.nhs.uk/conditions/acute-kidney-injury/
- Goyal A, Daneshpajouhnejad P, Hashmi M, Bashir K. Acute Kidney Injury . In: StatPearls [Internet]. StatPearls Publishing ; 2023.
- Rule AD, Lieske JC. The estimated glomerular filtration rate as a test for chronic kidney disease: Problems and solutions. Cleve Clin J Med. 2011;78(3):186-188. doi:10.3949/ccjm.78a.11004
- Baur D, Gladstone BP, Burkert F, et al. Effect of antibiotic stewardship on the incidence of infection and colonisation with antibiotic-resistant bacteria and Clostridium difficile infection: a systematic review and meta-analysis. Lancet Infect Dis. 2017;17(9):990-1001. doi:10.1016/S1473-3099(17)30325-0
- Clifford KM, Selby AR, Reveles KR, et al. The Risk and Clinical Implications of Antibiotic-Associated Acute Kidney Injury: A Review of the Clinical Data for Agents with Signals from the Food and Drug Administration’s Adverse Event Reporting System (FAERS) Database. Antibiotics. 2022;11(10):1367. doi:10.3390/antibiotics11101367
Charting the Course to Laboratory Excellence
Are you still using spreadsheets for your QC data and Charts?
You’ve been left behind.
But don’t worry!
Your laboratory’s ultimate ally in the quest for precision and excellence has arrived.
Acusera 24.7 is a tool that not only streamlines your QC data but also empowers you with a treasure trove of invaluable charts.
These charts are more than just numbers and lines; they are your secret weapon for troubleshooting, achieving accreditation, and driving continuous process improvement.
Acusera 24.7 doesn’t just offer charts. It offers a symphony of insights at your fingertips. From the precision of interactive Levey-Jennings charts to the competitive edge of performance summary charts for peer group comparison, from the rhythm of weekly mean charts to the clarity of reliable SD histograms – these charts are your compass in the world of quality control.
The best part?
You’re in control.
Tailor these charts to your unique needs, whether you’re dealing with single or multiple analytes, an abundance of QC lots, fixed or variable SDs, or need to pinpoint data within a specific date range.
Join us on a journey through the world of Acusera 24.7’s charts, where data becomes your strategic advantage, and discover why more laboratories are choosing Acusera 24.7 for QC data management every day.
Levey-Jennings Charts
Every laboratorian has seen countless Levey-Jennings charts and for good reason.
These charts are the unsung heroes of quality control in the laboratory.
They offer a visual snapshot of data over time, helping to detect trends, outliers, and systematic errors that might otherwise go unnoticed. Levey-Jennings charts are like the heartbeat monitor of your laboratory, providing real-time insights into the health of your analytical processes.
We’ve taken Levey-Jennings charts to the next level.
Our colourful graphs might look like they belong in a modern art museum, but trust me, they’re more than just eye candy.
Acusera 24.7’s Levey-Jennings charts are like the laboratory’s personal detective, sniffing out anomalies and shifts and making sure your QC data behaves.
Let’s have a look at what you can do with the Acusera 24.7 interactive Levey-Jennings charts.
The screenshot below shows a Levey-Jennings chart for a single analyte, with the date on the X-axis and SD on the Y-axis. On this chart, you can see data points displayed in different colours. Green data points indicate an acceptable result. Orange points show data that has triggered your predefined alert criteria, while red points are those that have broken your set rejection rules.
The lines marked on the chart below represent events that have been recorded. Instrument events such as calibration events or maintenance can be recorded to monitor their effects on your QC, allowing you to quickly see how these events relate to any deviations or improvements in your QC data. For example, after the event labelled ‘Reagent lot change’ you can see a series of alerts and failures. Marking this event on the chart allows for an at-a-glance explanation of this deviation. These events are completely customisable so you can record any relevant information you want!
Finally, data points that appear as a triangle indicate a comment has been added. What text is included in the comment is completely up to you!
The next screenshot below shows a Levey-Jennings chart containing QC data for all the tests included in the Clinical Chemistry Panel.
Acusera 24.7 panels allow you to group related tests together, helping increase the efficiency of your data review.
It looks great, right?
Maybe a little confusing.
The screenshot is perhaps a little deceptive.
When viewing these charts live, you can view the data as a whole, or home in on individual data sets by simply hovering over the data you want to see. You can also selected a deselect datasets at will by clicking on its name in the list below the chart.
The screenshot below shows an example of this.
All the charts we’ve looked at so far have had a fixed 3SD on the Y-axis.
For a more in-depth review of your data, you may wish to expand this axis.
With the click of a button, you can expand the Y-axis to include all your data points. See below for an example.
In some cases, you may wish to view this data displayed as ‘% Deviation’.
Again, with the click of a single button, you can convert the Y-axis to show just that, as shown below.
Performance Summary Charts
Peer group comparison of IQC data has a lot of benefits.
Comparing your data with other laboratories that use the same QC lot, instrument, method and more, can help you with troubleshooting and continuous process improvement.
The Acusera 24.7 Performance Summary Charts do all the work for you.
As shown in the screenshot below, these charts display your data and how it compares to your peers including mean, CV, and SD.
You can also view this data in a table to get a more detailed picture of your performance.
Like the Levey-Jennings charts, you can also combine this information for panels or a selection of multiple lots and analytes. You can see an example below:
Weekly Mean Charts
Weekly Mean Charts are one of the new features in our latest software release.
They allow you to view your weekly count of QC results for a specific instrument, assay, or lot.
Below is an example in a bar chart format.
You can also view this data as a line graph, which plots the weekly mean of results from multiple instruments using the same assay and QC lot, allowing a comprehensive overview of your QC data.
Or you can view your weekly means for a range of tests and panels.
Finally, the SD Histograms allow you to view the distribution of your results, for an overview of performance.
When used with Acusera 24.7’s suite of advanced statistical tools and reports, our charts can help you reduce the time you spend investigating non-conformances.
When the dreaded accreditation assessment approaches, you can relax. While others are scrambling to find documentation, you can rest assured that all the QC data you need is easily accessible.
Assessors love to see Acusera 24.7 load when they enter a laboratory because they understand how much easier QC management is when using our software.
We provide complete onboarding assistance and full training on the software for new customers while delivering prompt and effective customer support for existing users. The Acusera 24.7 and QC operations teams are always eager to help new and existing Acusera 24.7 users with any issues they experience.
To learn more about the features of this ground-breaking software, visit our website here.
Alternatively, feel free to reach out to us at marketing@randox.com for more information or to arrange a demo!
From Fear to Freedom: A QC Data Management Revolution
What if we told you we had a solution to the multitude of monotonous hours spent analysing reams of IQC data and could provide you with an intuitive tool packed with comprehensive and customisable reports, interactive charts, and automated statistical analysis to help improve your QC data management?
Perhaps it sounds too good to be true?
This time, it isn’t.
Uncertainty of Measurement. 6Sigma. QC Multi-rules. These words can strike fear into the hearts of even the most experienced laboratory staff.
With Acusera 24.7, we’ve reached under the bed and forced the monster that is advanced statistical analysis out into the cold.
Acusera 24.7 is a live, cloud-based, interlaboratory QC data management and peer group comparison software.
A mouthful. I know.
But let’s break it down
A live, cloud-based software means you can access your QC data from anywhere, anytime.
Bid farewell to the labyrinth of folders you hunt through when troubleshooting or looking for a specific dataset.
Interlaboratory management describes the momentous task many QC managers face – monitoring the QC performance of multiple laboratories in different locations, ensuring they all maintain the high standards required for accreditation and accurate patient results.
Unlike some big-name subscription services, we encourage you to use our software at different locations to help you monitor all your laboratories and instruments to see how their results stack up against one another.
Acusera 24.7 provides multiple levels of access which are completely customisable. This allows you to grant or restrict access to different parts of the software depending on what is required by your staff. This also allows QC managers to view data from all their sites in one location without needing multiple email chains from each laboratory.
Peer group comparison? Isn’t that what EQA is for?
Well, you would be right.
Yes, EQA does provide a comparison with your peer group, but it doesn’t have exclusive rights.
There are many benefits to comparing your IQC data with your peer group. The real-time comparison data aids with troubleshooting, or you can show off how great you are to your friends and colleagues.
You can select your peer group for an instrument, method and more, providing you with a comprehensive picture of how your laboratory performance compares to your peers using the same lot of control.
There are no submission deadlines. One less thing for you to worry about.
Still think it sounds too good to be true?
Then let’s look at some of the software features and how they can be used to make your daily QC data management easier.
Charts
For many laboratories, review of their QC data is a momentous task involving an abundance of printouts with different data tables and graphs and hastily scribbled notes going back maybe months, if not years.
With Acusera 24.7’s interactive Levey-Jennings charts, you can see the QC data from a specified date range. This helps visualise trends and biases over any period to simplify the troubleshooting and lot validation processes, or, can be used as evidence during accreditation assessments. These charts can be generated for a single analyte or for multiple analytes and QC levels.
You can also add events to the graph to record factors that might impact the performance of your analyser such as preventive maintenance, calibrations or switching QC lots. So, when you come to review the QC data and see a shift in the results, you can see at a glance if there was an explanation for the change in QC results.
What’s more, the points plotted on the chart will appear in orange or red if they trigger your alert or reject protocols respectively. Those that appear as a triangle indicate a comment is attached. Comments can be added to any data point directly on the Levey-Jennings chart, allowing you to record any information relevant to the data, saving you time, not to mention the cost of all those sticky notes.
This complements the Panel feature of the software. Within Acusera 24.7 you can create a panel of tests, for example, a Liver Function Test panel, grouping all the tests together. You can then view all the QC data for this panel at the click of a few buttons. Shown below is the collective data for a clinical chemistry panel.
When you do need the paper copy, all the charts and reports found in Acusera 24.7 can be exported to Excel or PDF for independent analysis or printing, making it easy to bring your data to meetings or for hardcopy filing and audits.
For peer group comparison, you can get a performance summary chart. This chart basically does the analysis for you! You define the date and time range, and the software looks at all the data points within it for you and your peer group, comparing individual data, means, CVs and SDs. Like our other charts, you can combine any number of these for multi-analyte analysis.
Advanced Statistics
Some people love statistics. Others can think of nothing worse.
Either way, there’s a lot of work involved in advanced statistical analysis.
Even if you’re in the love camp, you might find yourself sickened before you’ve finished this metaphorical jar of marmite.
The role of a pathology laboratory is not to run QC and show off their statistical skills, but to provide accurate and appropriate patient results.
As the old saying goes, time is money.
But in your case, time is the difference between a fast or delayed diagnosis for a patient.
This may impact their condition or treatment.
By making use of the suite of statistical options included in Acusera 24.7, including QC Multi-rules, 6Sigma and Uncertainty of Measurement, you can focus on providing the most accurate and efficient testing for patients.
Data Entry
To save even more time, Acusera 24.7 can be integrated with many LIMS or Middleware packages for fully automated data transfer. At a predefined time, your internal software will send your QC data to a shared folder on your network and from there to a Randox Cloud IP address, meaning we don’t go into your IT system and take anything; we won’t cause any information security problems. This data is then taken from the cloud and populated onto 24.7.
All this in less time than it takes you to say, ‘fully automated data transfer.’
You can also import your data through a semi-automated upload procedure. For this, the data is exported from your LIMS or middleware and imported manually to your Acusera 24.7 account using an EDI import file. Simply put, all you have to do is send the file, and the software will populate it onto the system. Alternatively, you can upload the data manually on the simple and intuitive data entry page.
Acusera 24.7, while comprehensive and initially daunting due to its vast array of features, is incredibly easy to use. The Acusera 24.7 and QC operations teams are always eager to help new and existing Acusera 24.7 users with any issues they experience. We provide complete onboarding assistance and full training on the software for new customers while delivering prompt and effective customer support for existing users.
We’ve only begun to cover the range of features available on Acusera 24.7 for QC data management! For more information or to arrange a demo, get in touch with our team at marketing@randox.com. Or, you can take a look at our website here.
Differentiating Viral from Bacterial Infections
Estimates claim that over 1.2 million people died in 2019 as a direct result of an antibiotic-resistant bacterial infection. Statistics show that up to 4.95 million deaths in the same year were associated with antimicrobial resistance (AMR)1. The overuse and misuse of antibiotics is considered to be the largest contributing factor to the rise of AMR. Antibiotics are effective at treating a wide range of bacterial infections, however, when used to treat viral infections, they have little to no effect. Even still, many physicians continue to prescribe so-called empirical antibiotics as an all-encompassing treatment strategy. In their defence, differentiating viral from bacterial infections can be troublesome. Traditional testing takes the form of paired serology, which requires patients to visit a healthcare facility twice during a 2–4-week period. Many of these infections have distressing symptoms, making this an unreasonable time-to-diagnosis period. Novel molecular techniques can reduce the time to result in the determination of many infections. However, some of these methods are associated with high false positive rates and low specificity resulting in further misuse of antibiotics.
Mxyovirus resistance protein A (MxA) is a biomarker associated with viral infections. It displays antiviral activity against positive, double-stranded RNA viruses and some DNA viruses2. In a study from earlier this year, MxA was used to differentiate viral from bacterial infections in a cohort of 61 adults with an AUROC of 0.9 and a sensitivity and specificity of 92.3% and 84.6% respectively3. An additional study, known as the TREND study, found that a cut-off of 430μg/L could effectively differentiate bacterial and viral infections with an AUROC of 0.9, a sensitivity of 92% and a specificity of 100%4.
C-reactive protein (CRP) is a non-specific acute phase protein which is associated with bacterial infection. However, CRP levels have also been shown to be elevated in response to various viral infections such as Influenza virus, malaria5 and SARS-COV-26, limiting its utility in differentiating the aetiology of an infection.
Using both biomarkers in combination can help physicians determine the true aetiology of infection with high specificity, supporting antimicrobial stewardship and reducing the harmful use of these drugs. Available on the VeraSTAT, Randox provides tests for MxA and CRP, which together provide a fast and accurate method of detection and differentiation of bacterial and viral infections from a small sample.
We have provided an educational guide which describes these biomarkers and their usefulness in the arena of viral and bacterial detection. If you’re interested in learning more, you can find our educational guide here.
Differentiating Viral from Bacterial Infections
Alternatively, don’t hesitate to browse our range on our website or get in touch with one of our team at marketing@randox.com who will be happy to help with any query you have!
References
- Murray CJL, Ikuta KS, Sharara F, et al. Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. The Lancet. 2022;399(10325):629-655. doi:10.1016/S0140-6736(21)02724-0
- Liao S, Gao S. MxA: a broadly acting effector of interferon-induced human innate immunity. Visualized Cancer Medicine. 2022;3:2. doi:10.1051/vcm/2022002
- Metz M, Gualdoni GA, Winkler HM, et al. MxA for differentiating viral and bacterial infections in adults: a prospective, exploratory study. Infection. Published online February 3, 2023. doi:10.1007/s15010-023-01986-0
- Rhedin S, Eklundh A, Ryd-Rinder M, et al. Myxovirus resistance protein A for discriminating between viral and bacterial lower respiratory tract infections in children – The TREND study. Clinical Microbiology and Infection. 2022;28(9):1251-1257. doi:10.1016/j.cmi.2022.05.008
- Joseph P, Godofsky E. Outpatient Antibiotic Stewardship: A Growing Frontier—Combining Myxovirus Resistance Protein A With Other Biomarkers to Improve Antibiotic Use. Open Forum Infect Dis. 2018;5(2). doi:10.1093/ofid/ofy024
- Paranga TG, Pavel-Tanasa M, Constantinescu D, et al. Comparison of C-reactive protein with distinct hyperinflammatory biomarkers in association with COVID-19 severity, mortality and SARS-CoV-2 variants. Front Immunol. 2023;14. doi:10.3389/fimmu.2023.1213246
Pursuing Perfection: Insights into Global IQC Practices
In a time when medical laboratory personnel are pushed to their limits, internal quality control and quality management are easy to consider a nuisance. However, these processes are vital to ensure accuracy and precision in the potentially life-saving tests performed in these laboratories. Most High-to-middle-income countries have strict regulations governing quality procedures in medical laboratories, but global standardisation in these areas is lacking. Over 70% of clinical decisions are based on laboratory testing but many clinicians are unaware of the accuracy and precision limitations associated with many of these tests. This places the responsibility on laboratory staff to ensure that all results provided to clinical decision-makers are as true as possible. For this, they rely on IQC and a robust quality management system.
To determine the state of the industry, a report by the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) Task Force on Global Laboratory Quality (TF-GLQ) surveyed over 100 IFCC full and affiliate members, receiving responses from 46 countries1. This survey consisted of a series of multiple-choice questions in relation to quality practices in their respective countries.
Findings by IFCC Task Force on Global Laboratory Quality
90% of respondents indicated that quality standards are in use in their country, despite being mandatory in only 46.7% of those countries.
These responses are encouraging showing that at least some level of predefined QC practice is implemented even in countries that do not legislatively mandate the inclusion of quality standards. This also hints that in those countries where it is not mandatory, it may soon become a requirement to adhere to a specified QC system. Nevertheless, in countries where regulatory measures are currently absent, the rigour of the implemented quality control procedures may not be adequate to ensure the accurate reporting of results.
42.5% of respondents indicated that IQC was not run in all laboratories in their country.
These respondents indicated that IQC is run in 50-99% of laboratories in their country. This less encouraging result shows that minimum IQC practices are not implemented globally. However, due to the multiple-choice nature of this survey, it is difficult to determine how drastic this issue is. Although it does raise the question of how these laboratories verify the precision of their results.
66.7% of respondents indicated that they use assay manufacturer quality control material.
This refers to first party quality control materials which are optimised by the manufacturer for use with a specific assay, instrument or method. These controls are often manufactured from the same material as the calibrator, making them less sensitive to subtle changes in performance, allowing them to mask weaknesses in the assay in question and therefore should be considered less effective options than third-party controls. Additionally, ISO15189:2022 encourage the use of third-party controls and require laboratories seeking accreditation that do not use third party controls to provide a sufficient explanation as to why this is the case.
60% of respondents indicated that not all laboratories in their country had written IQC policies and procedures.
This highlights an important aspect of a quality management system. Without written IQC policies and procedures it is almost impossible to standardise the IQC process and corrective action across laboratory staff, never mind on a national scale. Drafting this documentation can be cumbersome, however, many organisations can be contracted to assist with the drafting and implementation of these procedures for laboratories seeking to gain accreditation.
28.6% of respondents reported that manual interpretation of the IQC data was normal practice.
Manual data interpretation also poses challenges to the standardisation of IQC processes. Written IQC policies and procedures are crucial in implementing standard acceptance criteria for IQC results. Manual data interpretation also implements restrictions on the ability to carry out more advanced statistical analysis of the QC data.
Discussion
The implementation of robust IQC practices is crucial for ensuring the trueness and precision of the results produced by a laboratory. Used correctly, IQC can monitor variability caused by instrumentation and lot changes as well as various other sources of analytical error. ISO15189:2022 provides a thorough framework for designing rigorous IQC policies and procedures, highlighting key areas such as the use of third party QC material, levels of QC material, the frequency at which IQC should be completed, matrix composition, acceptance/rejection criteria and non-conformance procedures. For more information on ISO15189:2022 accreditation, take a look at our educational guide ISO15189:2022 Updates.
The results from this survey conducted by IFCC show a clear disparity between IQC processes around the globe, displaying differences in requirements, recommendations, and legislation. Standardisation of IQC is not without its challenges. However, by striving to achieve the highest possible levels of quality, and following the guidance laid out in ISO15189:2022, laboratories can be confident in the results they provide to clinicians.
Acusera Quality Control
The Acusera range offers unbiased, independent third party quality controls for medical and research laboratories of all shapes and sizes. Our assayed controls are provided with target values for most commercially available analysers, ensuring that your test menu will be covered. With enhanced stability, commutability and consolidation, all our controls are manufactured to provide a clinically relevant challenge to your test method, aiding in ISO15189 accreditation. For more specialist laboratories, our teams are happy to discuss your requirements and help to provide bespoke quality control material, providing an extremely flexible QC range.
Acusera 24.7
Designed for use with the Acusera range of third party controls, the Acusera 24•7 software will help you monitor and interpret your QC data. Access to an impressive range of features, including interactive charts, the automatic calculation of Measurement Uncertainty & Sigma Metrics and live peer group data generated from our extensive database of laboratory participants, ensures Acusera 24•7 is the most comprehensive package available. For laboratories performing manual review of their IQC data, Acusera 24•7 provides a comprehensive yet easy-to-use platform for advanced statistical analysis and monitoring of these data.
For more information on our Acusera range of IQC material, or Acusera 24•7, feel free to reach out to us at marketing@randox.com or alternatively, browse our range of literature at the QC Resource Hub
References
- Wheeler SE, Blasutig IM, Dabla PK, et al. Quality standards and internal quality control practices in medical laboratories: an IFCC global survey of member societies. Clinical Chemistry and Laboratory Medicine (CCLM). 2023;0(0). doi:10.1515/cclm-2023-0492
RX Imola: Inflammatory Biomarkers in COVID-19
Over the course of human history, few events have had such a dramatic impact as the COVID-19 pandemic. According to the World Health Organization (WHO), as of 12th July 2023, the SARS-CoV-2 virus has claimed almost 7 million lives and figures continue to rise1. While many who become infected are only subject to mild symptoms, those who develop a more severe form of the infection are encumbered with a debilitating flu-like condition, often requiring days, if not weeks of bed rest. In a paper from June 20232, the Rx Imola was used to study C reactive protein concentrations, along with other biomarkers, in mild and severe COVID-19 patients in order to develop novel risk stratification methods for this potentially life-threatening viral infection.
The impact on healthcare services around the world cannot be understated. In developed countries, access to services for both COVID-related and other conditions took a catastrophic hit. In low-to-middle-income countries, the impact has been even more distressing, all but eliminating basic medical care in favour of combating COVID-19, partly due to inferior resources and facilities3.
In times of medical emergency, it is crucial to have an efficient and effective means of stratifying the risk to patients and a process for suitably categorising those into the least and most at risk of severe complications or death. Due to the rate at which COVID-19 spread, unfortunately, the world lacked these mechanisms for SARS-CoV-2, resulting in mass hospital overpopulation, cancelled appointments for other life-threatening conditions and ultimately the staggering mortality statistics we’ve been bombarded with since January 2022. This prompted an unprecedented surge in medical research and major advances in testing capabilities, giving us new methods of detecting SARS-CoV-2 and determining the risk posed to individuals.
One such investigation, by Paranga et al., (2023) studied a total of 13 biomarkers to determine which could accurately differentiate mild, moderate, and severe cases and identify biomarkers which were good predictors of fatality2. C reactive protein (CRP) was the best-described biomarker relating to COVID-19 throughout the pandemic. This paper compares it to 12 other biomarkers including suPAR, sTREM-1, ferritin, MCP-1 and Lactate dehydrogenase. Of these, it was discovered that CRP was clearly the most effective biomarker for differentiating mild from severe cases, with concentrations in those with severe infection being, on average, 45% higher than in those with mild symptoms2. Additionally, the authors discovered that CRP levels were not significantly affected by age, a factor known to affect the inflammation and immune responses, providing a powerful and inclusive risk stratification tool. Some of the additional conclusions drawn from this paper can be seen below2:
- Lactate dehydrogenase, sTREM-1 and HGF were good predictors of mortality in COVID-19.
- suPAR was identified as a crucial molecule in characterising Delta variant infection and mortality.
- The initial values of inflammatory biomarkers were good to excellent predictors of disease severity in COVID-19 patients.
- Disease severity and mortality are associated with a higher rate of comorbidities including thrombocytopenia and other blood diseases, circulatory and respiratory system diseases and liver diseases such as cirrhosis.
So, what is CRP and how does it become elevated in response to a SARS-CoV-2 infection? CRP is a non-specific, acute-phase protein, meaning its concentration is altered in response to inflammation4. The acute respiratory distress syndrome induced by SARS-CoV-2 is, in part, a result of the hyperinflammation caused by the virus2. CRP is a well-characterised inflammatory biomarker and is therefore well-suited for identification and risk stratification in an emerging disease.
This investigation2 utilised the RX Imola, a rapid, comprehensive clinical chemistry platform, to quantify CRP. With the RX Imola, laboratories can gain access to the world’s largest clinical chemistry test menu covering routine chemistries as well as specific proteins, lipids, and more providing a cost-effective and user-friendly platform. With 60 cooled reagent positions and a sample carousel with 20 cooled positions for controls and calibrators, the RX Imola is an ideal solution for small to medium-throughput laboratories seeking an innovative and reliable clinical chemistry system. Randox also supplies suitable, high-quality reagents, and through Acusera, state-of-the-art controls and calibrators, completing the clinical chemistry portfolio.
References
1. World Health Organisation. WHO Coronavirus (COVID-19) Dashboard. https://covid19.who.int/.
2. Paranga TG, Pavel-Tanasa M, Constantinescu D, et al. Comparison of C-reactive protein with distinct hyperinflammatory biomarkers in association with COVID-19 severity, mortality and SARS-CoV-2 variants. Front Immunol. 2023;14. doi:10.3389/fimmu.2023.1213246
3. Jain P. Impact of COVID-19 Pandemic on Global Healthcare Systems and the role of a new era of global collaborations. Sushruta Journal of Health Policy & Opinion. 2021;14(3):1-5. doi:10.38192/14.3.2
4. Nehring S. C Reactive Protein . https://www.statpearls.com/articlelibrary/viewarticle/18744/.
World Hepatitis Day 2023
Introduction
World Hepatitis Day, observed on July 28th, serves as a crucial reminder of the ongoing battle against hepatitis (HBV), a viral infection that affects millions of people worldwide. In 2019, it was estimated that 296 million people were living with chronic hepatitis B, resulting in over 800,000 fatalities1. In this article, we will delve into the intricate mechanisms behind hepatitis, explore the viral species responsible for its occurrence, discuss methods for diagnosis, and shed light on treatment and management strategies.
Understanding Hepatitis
Hepatitis refers to the inflammation of the liver, often caused by viral infections. Among the primary hepatitis viruses are Hepatitis A, B, C, D, and E, each with distinct modes of transmission and characteristics2.
Mechanisms of Hepatitis Infection
Hepatitis A and E: Hepatitis A and E viruses are primarily transmitted via the faecal-oral route, often through contaminated food or water. Ingestion of these viruses leads to acute infection, and while self-limiting in most cases, they can cause significant morbidity and mortality in certain populations5,6.
Hepatitis B, C, and D: Hepatitis B, C, and D viruses are predominantly spread through blood and bodily fluids. Hepatitis B can also be transmitted from mother to child during childbirth which in endemic areas, HBV infection from mother to child transmission accounted for approximately half of chronic infections. These viruses can cause chronic infections, leading to long-term liver damage, cirrhosis, and an increased risk of hepatocellular carcinoma7,8.
Diagnosis of Hepatitis
Accurate and timely diagnosis of hepatitis is crucial for appropriate management. Diagnostic methods include:
Serology: Serological tests, such as enzyme immunoassays, are employed to detect specific viral antigens or antibodies in blood samples, aiding in the identification of different hepatitis viruses and determining the stage of infection9.
Nucleic Acid Testing: Highly sensitive molecular techniques like polymerase chain reaction (PCR) enable the detection and quantification of viral genetic material, aiding in the diagnosis and monitoring of chronic hepatitis10.
Treatment and Management of Hepatitis
The management of hepatitis depends on several factors, including the virus involved, the stage of infection, the presence of co-infections, and the individual patient’s health status. Treatment strategies encompass:
Antiviral Medications: For hepatitis B and C, antiviral drugs such as interferons and direct-acting antivirals have revolutionized the treatment landscape, offering higher cure rates and improved outcomes11,12.
Supportive Care: Hepatitis patients may require supportive care to alleviate symptoms, maintain proper nutrition, and manage complications. Vaccination against hepatitis A and B is highly recommended for prevention13.
Liver Transplantation: In cases of end-stage liver disease or hepatocellular carcinoma resulting from chronic hepatitis, liver transplantation may be considered a lifesaving option14.
Randox Hepatitis Solutions
Acusera
Acusera provides a range of positive and negative serology controls comprising various infectious diseases including Hepatitis. The table below details the suitable controls, and more information can be found on our website: Serology Quality Controls – Randox Laboratories
RIQAS
The RIQAS HIV/Hepatitis EQA programme is designed to monitor the performance of tests used to detect HIV/Hepatitis antibodies and specific antigens. All samples are conveniently supplied liquid ready-to-use and are suitable for qualitative methods of analysis.
Parameters:
- Anti-HIV-1
- Anti-HCV
- Anti-HTLV-II
- HBsAg
- Anti-HIV-2
- Anti-HBc
- Anti-HTLV-1&2 (combined)
- Anti-HIV-1&2 (combined)
- Anti-HTLV-I
- Anti-CMV
- Anti-HAV IgM
- Anti-HAV (Total)
- Anti-HBc (Total)
- Anti-HBe (Total)
- Anti-HBs (Total)
- P24
For more information, please visit our website at: HIV Hepatitis EQA | RIQAS (randox.com)
Qnostics
Monitoring for the presence of Blood Borne Virus (BBV) nucleic acid is an essential parameter in guiding clinical treatment and patient outcomes. The use of appropriate quality control measures is important in ensuring the appropriate daily performance of the molecular assay used in the laboratory independent of the technology.
Qnostics’ Blood Borne Virus Molecular Controls comprises a range of pathogens which are classically detected directly from the blood including those related to hepatitis. The table below lists the Qnostics products related to hepatitis testing. For more information visit our website: Qnostics | Molecular Infectious Disease Controls – Randox Laboratories
QCMD
QCMD is a world-leading External Quality Assessment (EQA) / Proficiency Testing (PT) scheme, dedicated to improving the quality of molecular diagnostic assays used in the detection of infectious diseases. With an extensive database of over 2000 participants in over 100 countries, QCMD is one of the largest providers of molecular EQA in the field of molecular diagnostics. QCMD programmes related to hepatitis testing are listed below:
- HBV Drug resistance Typing EQA programme.
- HCV Drug resistance Typing EQA programme.
- Hepatitis B Virus DNA EQA Programme
- Hepatitis B Virus Dried Blood Spot EQA Pilot Study
- Hepatitis B virus Genotype EQA Programme
- Hepatitis C Virus Dried Blood Spot EQA Pilot Study
- Hepatitis C Virus RNA EQA Programme
- Hepatitis C virus Genotype EQA Programme
- Hepatitis D Virus EQA Programme
- Hepatitis E virus RNA EQA Programme
For more information on any of these EQA programmes please visit: QCMD – Molecular EQA Scheme | Randox Quality Control
Conclusion
World Hepatitis Day serves as a reminder of the global impact of hepatitis and the urgent need to raise awareness, prevent transmission, and improve the diagnosis and management of this disease. By understanding the mechanisms, bacterial species involved, diagnostic techniques, and treatment approaches, we can work towards a future free from the burden of hepatitis. Let us unite in our efforts to combat this disease and strive for a healthier world.
If you’d like to find out more about hepatitis or the diagnosis and testing of hepatitis, please visit our website. If you’d like more information on how Randox can improve hepatitis testing in your laboratory, please reach out to marketing@randox.com.
References
- World Health Organization. World Health Statistics 2023. World Health Organization; 2023. https://www.who.int/publications/i/item/9789240074323
- World Health Organization. Hepatitis. https://www.who.int/news-room/fact-sheets/detail/hepatitis-a. Published 2017. Accessed June 9, 2023.
- Wan Z, Wang X. Bacterial Hepatitis. In: Encyclopedia of Medical Microbiology. Elsevier; 2020:110-117.
- Russo TA, McFadden DC. Bacterial and fungal infections in patients with cirrhosis. Clin Liver Dis. 2019;14(2):71-74.
- World Health Organization. Hepatitis E. https://www.who.int/news-room/fact-sheets/detail/hepatitis-e. Published 2018. Accessed June 9, 2023.
- Rakesh S, Pekamwar SS. Hepatitis A. In: StatPearls [Internet]. StatPearls Publishing; 2020.
- World Health Organization. Hepatitis B. https://www.who.int/news-room/fact-sheets/detail/hepatitis-b. Published 2021. Accessed June 9, 2023.
- World Health Organization. Hepatitis D. https://www.who.int/news-room/fact-sheets/detail/hepatitis-d. Published 2021. Accessed June 9, 2023.
- Alfaresi MS, Elkoush AA, Khan AS. Serological diagnosis of viral hepatitis. J Clin Transl Hepatol. 2017;5(4):343-359.
- European Association for the Study of the Liver. EASL Recommendations on Treatment of Hepatitis C. J Hepatol. 2017;66(1):153-194.
- European Association for the Study of the Liver. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol. 2017;67(2):370-398.
- Vermehren J, Sarrazin C. New HCV therapies on the horizon. Clin Microbiol Infect. 2011;17(2):122-134.
- World Health Organization. Hepatitis A. https://www.who.int/news-room/fact-sheets/detail/hepatitis-a. Published 2020. Accessed June 9, 2023.
- Kim WR, Terrault NA. Hepatocellular carcinoma and liver transplantation. Clin Liver Dis. 2018;22(2):381-394.
Exploring the Intricacies of Bile Acids: Understanding Their Role in Metabolism and Intrahepatic Cholestasis of Pregnancy
Bile acids (BAs) are fascinating molecules that play a pivotal role in our bodies metabolic processes. From aiding in the digestion of lipids to regulating essential metabolic pathways, BAs have garnered significant interest among researchers and healthcare professionals. In this article, we will delve into the structural and functional aspects of bile acids and explore their significance in a condition called intrahepatic cholestasis of pregnancy (ICP). For additional information, we encourage you to take a look at our latest educational guide: 5th Generation Bile Acids & Intrahepatic Cholestasis of Pregnancy. So, let’s unravel the secrets of bile acids and their impact on our health!
Understanding Bile Acids
Bile acids belong to a diverse family of bile salts, characterised by their planar and amphipathic nature. They possess a hydrophilic hydroxyl and a hydrophobic methyl group, conferring their unique amphipathic properties. These properties allow bile acids to emulsify and solubilize lipids, facilitating their digestion and absorption1.
Bile acids are primarily synthesized in the liver through two pathways: the classic (neutral) pathway and the alternate (acidic) pathway. The classic pathway involves the hydroxylation of cholesterol, while the alternate pathway utilizes oxysterols as precursors. These pathways produce primary bile acids, which are further modified to generate secondary and tertiary bile acids2.
Importance of Bile Acids in Metabolism
Bile acids serve multiple functions in our bodies. Firstly, they emulsify dietary fats, breaking them down into smaller droplets that can be efficiently digested by pancreatic enzymes. Additionally, bile acids are crucial for the absorption of fat-soluble vitamins, such as vitamins A, D, E, and K. These vitamins are incorporated into micelles, facilitated by the presence of bile acids, enabling their uptake3.
Furthermore, bile acids exhibit signalling activity through various receptors, influencing metabolic responses. One key receptor associated with bile acid metabolism is the Farnesoid X receptor (FXR). Activation of FXR regulates bile acid synthesis, delivery, and clearance, maintaining their levels within a safe range. FXR also modulates lipid transport and metabolism, as well as hepatic gluconeogenesis. Another important receptor is TGR5, which influences vasodilation, gallbladder function, and exerts anti-inflammatory effects1.
Intrahepatic Cholestasis of Pregnancy
During pregnancy, the metabolic processes in the liver undergo significant adaptations to accommodate the growing foetus. One condition that can arise during pregnancy is intrahepatic cholestasis, commonly known as ICP. It is a multifactorial disorder characterised by elevated levels of bile acids in the blood, particularly chenodeoxycholic acid (CDCA) and cholic acid (CA)4.
ICP manifests in the second or third trimester and can lead to various symptoms such as pruritus (itching), abnormal liver enzyme levels, jaundice, abdominal pain, and depression. The exact mechanisms underlying ICP are not fully understood, but it is believed that elevated bile acid levels may have adverse effects on the cardiovascular system of the foetus, potentially leading to stillbirth or preterm birth5.
The detection and monitoring of ICP are essential for managing the condition and ensuring the well-being of both the mother and the foetus. Total bile acid (TBA) concentration is a commonly measured parameter to assess the severity of ICP. Monitoring TBA levels can aid in identifying potential risks and enabling timely interventions5.
Introducing the 5th Generation Total Bile Acids Assay
To facilitate the accurate quantification of total bile acids in serum and plasma, the 5th Generation Total Bile Acids Assay has emerged as a reliable and advanced diagnostic tool. This assay utilizes a highly sensitive enzymatic cycling method to measure total bile acid levels, providing precise and reproducible results. With its improved sensitivity and specificity, the 5th Generation Total Bile Acids Assay offers a valuable tool for the early detection and monitoring of intrahepatic cholestasis of pregnancy.
The assay is easy to use and can be incorporated into routine laboratory workflows. It requires a small sample volume, making it convenient for both patients and healthcare professionals. The assay provides rapid results, allowing for prompt diagnosis and timely intervention when necessary.
By accurately quantifying total bile acid levels, the 5th Generation Total Bile Acids Assay aids in assessing the severity of ICP and monitoring the response to treatment. This information is vital for guiding clinical decisions and optimizing patient care during pregnancy.
Furthermore, the assay can contribute to ongoing research on bile acids and their role in ICP. By analysing a larger population and monitoring the dynamics of bile acid levels, researchers can gain deeper insights into the mechanisms underlying this condition and explore potential therapeutic targets.
Assay Principle
Two reactions are combined in this kinetic enzyme cycling method. In the first reaction, bile acids are oxidised by 3-α hydroxysteroid dehydrogenase with the subsequent reduction of Thio-NAD to Thio-NADH. In the second reaction, the oxidised bile acids are reduced by the same enzyme with the subsequent oxidation of NADH to NAD. The rate of formation of Thio-NADH is determined by measuring the specific absorbance change at 405nm. Enzyme cycling means multiple Thio-NADH molecules are generated from each bile acid molecule giving rise to a much larger absorbance change, increasing the sensitivity of the assay.
In conclusion, understanding the intricacies of bile acids is essential for comprehending their impact on our metabolism and health. Intrahepatic cholestasis of pregnancy is a condition that warrants attention, and accurate measurement of total bile acid levels is crucial for its diagnosis and management. The 5th Generation Total Bile Acids Assay offers an advanced and reliable solution for assessing bile acid levels, enabling timely interventions, and improving patient outcomes. With ongoing research and advancements in diagnostic techniques, we can continue to unravel the complexities of bile acids and enhance our understanding of their role in health and disease.
Don’t underestimate the strength of knowledge and awareness. Empower yourself, stay informed, and prioritize your health and well-being!
If you’d like to learn more about Bile Acids and ICP we encourage you to read our new educational guide, 5th Generation Bile Acids & The Importance of Of Intrahepatic Cholestasis of Pregnancy
If you would like an additional information on our 5th Generation Total Bile Acids Assay, or anything else, don’t hesitate to reach out the marketing@randox.com. Additionally, feel free to visit our Reagent resource hub where you will find all of our brochures, support tools and a collection of educational material, to aid you in maintaining the highest possible levels of quality.
References
- McGlone ER, Bloom SR. Bile acids and the metabolic syndrome. Annals of Clinical Biochemistry. 2019;56(3):326-337. doi:https://doi.org/10.1177/0004563218817798
- Chiang JYL, Ferrell JM. Bile Acid Metabolism in Liver Pathobiology. Gene Expression. 2018;18(2):71-87. doi:https://doi.org/10.3727/105221618×15156018385515
- Chiang JYL. Bile Acid Metabolism and Signaling. Comprehensive Physiology. 2013;3(3). doi:https://doi.org/10.1002/cphy.c120023
- Di Mascio D, Quist-Nelson J, Riegel M, et al. Perinatal death by bile acid levels in intrahepatic cholestasis of pregnancy: a systematic review. The Journal of Maternal-Fetal & Neonatal Medicine. Published online November 19, 2019:1-9. doi:https://doi.org/10.1080/14767058.2019.1685965
- Piechota J, Jelski W. Intrahepatic Cholestasis in Pregnancy: Review of the Literature. Journal of Clinical Medicine. 2020;9(5):1361. doi:https://doi.org/10.3390/jcm9051361
A Comprehensive Guide to External Quality Assessment Programmes
The importance of External Quality Assessment (EQA) programmes in the realm of medical laboratories is beyond dispute. These programmes serve as external control mechanisms, underpinning the accuracy and reliability of diagnostic tests carried out by laboratories across the globe. By participating in EQA programmes, laboratories gain the ability to monitor their proficiency, identify areas for improvement, enhance their analytical performance, and above all, ensure top-tier patient care.
Today, we find ourselves faced with a multitude of EQA programmes, each touting its own, unique features and benefits. Therefore, the question that naturally follows is – how do you choose the right EQA programme for your laboratory?
Understand Your Laboratory’s Requirements
The first step towards selecting an EQA programme is to clearly understand the requirements of your laboratory. These requirements could encompass the range of tests performed, the desired frequency of assessment, and the specific areas where your lab wishes to improve
Examine the EQA Programmes
The next step is to critically examine each EQA programme. Look at the range of tests they cover, the frequency of their assessments, the type of samples they use, and their approach towards feedback and improvement.
Reporting
One of the most critical aspects of an EQA programme is the results reporting mechanism. This mechanism should provide comprehensive and constructive feedback, highlighting areas of improvement, and offering guidance on how to enhance performance. It is also essential to consider the frequency of reporting. More frequent reporting allows laboratories to identify problems and implement corrective actions swiftly, aiding in the continuous improvement of a laboratory and the confident delivery of accurate patient results.
Accreditation
The accreditation of the EQA programme should also be evaluated. Superior programmes are accredited to ISO17043:2010. Participation in an accredited EQA programme is mandatory under ISO15189:2022 accreditation. Choosing a scheme accredited to ISO17043 ensures that the programme has been rigorously evaluated and meets the necessary criteria of a high-quality EQA programme.
Cost-effectiveness
The cost of the EQA programme should be compared to the benefits your laboratory will reap from participating in the scheme. Although cost should not be the sole determining factor, it’s a crucial element to consider. Factors such as consolidation and number of registrations are key areas where many providers differ.
Customer Support
Finally, it’s vital to consider the customer support provided by the EQA programme. Adequate support will ensure that any issues or queries are addressed in a timely and efficient manner
Our latest educational guide Choosing the Right EQA Programme has been constructed to help you with this decision. Providing more detail on the points discussed above and more, this guide displays how the world-renowned RIQAS EQA programmes can help you maximise the accuracy of your laboratory results and achieve ISO15189:2022 accreditation.
In conclusion, selecting the right EQA programme requires a careful and thorough evaluation of several factors. By taking the time to understand your laboratory’s needs, scrutinising each EQA programme, and considering factors such as reporting, accreditation, cost, and customer support, you can make a well-informed decision that will significantly enhance the proficiency of your laboratory and the quality of patient care.
Remember, the primary objective of an EQA programme is to help your laboratory improve. Therefore, the right EQA programme for your laboratory is the one that best assists you in achieving this objective.
Prostate-specific Antigen & Prostate Cancer
Prostate cancer is the most common form of cancer in men. In the UK, 1 in every 8 men will be diagnosed with the condition within their lifetime, resulting in around 12’000 deaths per year1. Prostate-specific antigen is a major protease found in semen which functions to cleave semeogelins into smaller polypeptides resulting in the liquefication of semen2.
This week, we had the pleasure of welcoming Dr Floris Helmich, who discussed laboratory imprecision relating to Prostate-specific antigen (PSA) and prostate cancer in our latest webinar. Dr Helmich took the time out of his busy schedule to present his experience in PSA quantification and the importance of quality control in yielding accurate and precise results as well as discussing some of the experimental techniques he has found useful in identifying the source of bias laboratory testing. Dr Helmich also discussed the ambiguity relating to reporting ranges and how bias can affect the results of laboratory PSA testing.
What is PSA?
PSA is an enzyme produced by the prostate ductal and acinar epithelium where it is secreted into the lumen before it is used to liquefy semen. Once PSA enters circulation, most are bound to protease inhibitors, however, some remain inactive and circulate in the lumen as free PSA2.
PSA levels in men vary depending on their age. Typically, men between the ages of 50 and 69 should have a PSA level below 3ng/ml. If the PSA concentration exceeds 3ng/ml, it could be a potential indicator of prostate cancer3. However, the challenge with using PSA as the sole monitoring method for prostate cancer is the relatively high false positive rate associated with it. A higher PSA concentration can also be attributed to conditions such as an enlarged prostate, prostatitis, or a urinary tract infection4.
Research indicates that 1 out of 4 men with elevated PSA levels will actually have prostate cancer. Additionally, it has been observed that approximately one in every seven men diagnosed with prostate cancer will maintain normal PSA levels3. These findings highlight the limitations of relying solely on PSA screening for prostate cancer diagnosis. As a result, some countries have started to limit their recommendations regarding PSA-based prostate cancer diagnosis.
In response to these limitations, other countries have chosen to maintain their recommendations for PSA testing but are augmenting the guidelines by incorporating additional criteria to ensure more accurate diagnoses.
Elevated PSA
Elevated levels of PSA should not always be automatically interpreted as a sign of prostate cancer. In older men, one common cause of elevated PSA is benign prostatic hyperplasia (enlarged prostate). Additionally, prostatitis, which refers to inflammation of the prostate, can contribute to an increase in PSA concentration3. It’s important to consider other potential factors that can lead to elevated PSA levels, such as urinary tract infections, recent sexual activity, natural age-related increases, or injury to the groin area5.
Therefore, when assessing PSA levels, it is crucial to recognize that various non-cancerous conditions can also result in elevated PSA. It is recommended to consult healthcare professionals who can evaluate the individual’s medical history, perform further diagnostic tests, and consider other clinical factors to accurately determine the underlying cause of elevated PSA and make informed decisions about the next steps in diagnosis and treatment.
Ultra-low PSA concentrations
The diagnostic accuracy of PSA concentration for prostate cancer is known to be limited. However, there is a clear association between PSA levels and prostate cancer, which confirms it as a valuable tool for risk stratification and diagnosis when used in conjunction with other established factors.
PSA testing also plays a crucial role in monitoring patients who have undergone treatment for prostate cancer. In cases where the patient is deemed cancer-free, their PSA levels should decrease to within the normal range. Following radical prostatectomy (removal of the entire prostate), PSA levels should ideally be undetectable. Post-radiotherapy, it is expected that PSA levels will reach their lowest point (nadir) within 12-18 months. However, it’s important to note that in some cases, a temporary spike in PSA concentration has been observed after radiotherapy. This spike should not be immediately interpreted as recurrent cancer, but these patients should be closely monitored.
If PSA concentrations rise above 2.0ng/ml after radiotherapy, further testing is recommended to assess the possibility of recurrent cancer. Close monitoring and additional evaluations will help healthcare professionals make accurate and timely decisions regarding the patient’s ongoing treatment and care6
Guidelines
Different countries offer varying guidance in relation to Ultra-low PSA testing. The table below details some of these recommended guidelines:
| Guidelines | Description |
| American Urology Association 7 | PSA concentrations of >0.2ng/ml, followed by a subsequent confirmatory >0.2ng/ml result should be considered biochemical recurrence. However, a cut-off of 0.4ng/ml may better predict metastatic relapse. |
| European Association of Urology8 | A detectable PSA indicating relapse should be differentiated from a clinically meaningful relapse. PSA thresholds that predict further metastasises are:
Post-RP = >0.4ng/ml Post-RT = nadir + 2ng/ml |
| Prostate Cancer Foundation1 | Post-RP = PSA 0.2ng/ml is indicative of biochemical recurrence
Post-RT = PSA nadir + 2ng/ml is indicative of biochemical recurrence |
Randox Ultra-low PSA Control
We are excited to introduce Randox’s latest innovation, the Ultra-low PSA Control, designed to assist in the precise quantification and monitoring of ultra-low levels of PSA in post-therapy prostate cancer patients. This control has been specifically optimized for use on Roche systems, ensuring exceptional performance and compatibility. Moreover, it is versatile enough to be utilized on various other platforms, making it the sole control available on the market for measuring ultra-low levels of PSA across a range of instruments.
With the Acusera Ultra-low PSA Control, healthcare professionals can achieve accurate and reliable results, enabling them to monitor the progress and treatment response of prostate cancer patients with heightened sensitivity. With a clinically relevant concentration of approximately 0.055ng/ml, this advancement in control technology contributes to enhanced patient care and supports medical professionals in making informed decisions regarding treatment adjustments or further interventions.
Randox’s commitment to innovation and precision in diagnostic solutions continues with the Ultra-low PSA Control, empowering laboratories to deliver high-quality and dependable PSA measurements, even at the ultra-low levels required for post-therapy monitoring.
Take a look at our webinar, Laboratory Imprecision in Relation to PSA and Prostate Cancer Follow-up, with Dr Floris Helmich to learn about how his clinical laboratory deals with bias at quality control relating to Ultra-low PSA quantification
If you’d like to learn more about PSA testing and prostate cancer, we encourage you to read our new educational guide, Ultra-low PSA and Prostate Cancer
If you would like an additional information on our Ultra-low PSA Control, or anything else relating to Quality Control, don’t hesitate to reach out the marketing@randox.com. Additionally, feel free to visit our QC resource hub where you will find all of our brochures, support tools and a collection of educational material, to aid you in maintaining the highest possible levels of quality.
References
- Prostate Cancer Foundation. About prostate cancer. Prostate Cancer UK. Published 2023. https://prostatecanceruk.org/prostate-information-and-support/risk-and-symptoms/about-prostate-cancer
- Balk SP, Ko YJ, Bubley GJ. Biology of Prostate-Specific Antigen. Journal of Clinical Oncology. 2003;21(2):383-391. doi:https://doi.org/10.1200/jco.2003.02.083
- NHS Choices. Should I have a PSA test? – Prostate cancer. NHS. Published 2019. https://www.nhs.uk/conditions/prostate-cancer/should-i-have-psa-test/
- Isono T, Tanaka T, Kageyama S, Yoshiki T. Structural Diversity of Cancer-related and Non-Cancer-related Prostate-specific Antigen. Clinical Chemistry. 2002;48(12):2187-2194. doi:https://doi.org/10.1093/clinchem/48.12.2187
- Mejak SL, Bayliss J, Hanks SD. Long Distance Bicycle Riding Causes Prostate-Specific Antigen to Increase in Men Aged 50 Years and Over. Steyerberg EW, ed. PLoS ONE. 2013;8(2):e56030. doi:https://doi.org/10.1371/journal.pone.0056030
- Santis D, Gillessen S, Grummet J, et al. EAU-EANM-ESTRO-ESUR-ISUP-SIOG Guidelines on Prostate Cancer.; 2023.
- AUA. Advanced Prostate Cancer: AUA/ASTRO/SUO Guideline (2020) – American Urological Association. www.auanet.org. Published 2023. https://www.auanet.org/guidelines-and-quality/guidelines/advanced-prostate-cancer
- Sindhwani P, Wilson CM. Prostatitis and serum prostate-specific antigen. Current Urology Reports. 2005;6(4):307-312. doi:https://doi.org/10.1007/s11934-005-0029-y
