Forumlabo - LYon
  • News
    • Featured Articles
    • Product News
    • E-News
  • Magazine
    • About us
    • Digital edition
    • Archived issues
    • Free subscriptions
    • Media kit
    • Submit Press Release
  • White Papers
  • Events
  • Suppliers
  • E-Alert
  • Contact us
  • FREE newsletter subscription
  • Search
  • Menu Menu
Clinical Laboratory int.
  • Allergies
  • Cardiac
  • Gastrointestinal
  • Hematology
  • Microbiology
  • Microscopy & Imaging
  • Molecular Diagnostics
  • Pathology & Histology
  • Protein Analysis
  • Rapid Tests
  • Therapeutic Drug Monitoring
  • Tumour Markers
  • Urine Analysis

Archive for category: Featured Articles

Featured Articles

Brian Moore

Helping elite athletes to give a peak performance

, 26 August 2020/in Featured Articles /by 3wmedia

According to applied physiologist Dr Brian Moore, and Dr Andrew Hodgson, Consultant Physician (Haematology) – co-founders of the Irish company ORRECO – one of the most difficult elements of competing in sport at a world class level is to balance training hard whilst ensuring adequate recovery. Dr Moore and his integrated team of high performance practitioners advised Olympic medalists and competitors at the last three Olympic games, and will do the same at the London Olympic games this year. CLi spoke to Dr Moore and his team to find out more about ORRECO’s mission and the methods it uses to help athletes reach peak performance without overtraining.

Q. Could you first tell us a little about your company. What inspired you to set up ORRECO and what did you hope to achieve? Briefly how does the company operate?
ORRECO was founded with the aim of joining the disciplines of clinical and sports haematology to deliver a unique proposition for world sport. We facilitate blood and saliva analysis for some of the world’s best athletes from an administrative base on Ireland’s western coast – the Innovation Centre at the Institute of Technology, Sligo.

Analysis occurs through a global network of partner laboratories that are located close to training (altitude, warm weather) and competition (World Cup, Championship, Olympic) venues. Results are reported in real time through our software solution DAVE (Download, Analyse, Validate and Export your results) to allow team physicians, coaches and performance staff to review information immediately and compare the results to an athlete’s performance. We cross-reference the results with training and competition data, (e.g. speed and power, GPS tracking) to understand the individual’s adaptation to training.

Recognising that testing and result reporting are just one part of the solution; we also provide a consultancy service for elite athletes and their teams. Our performance staff assists in interpretation and comparison of results against sports-specific reference ranges, as well as provides practical guidance and interventions where needed. This includes nutritional support, training-plan modification and more. Rather then rely on one specific biomarker, we use multiple assays that are aggregated by our bio-statisticians and map the athlete on a range from ‘well’ to ‘unwell’, and, from ‘peak performance’ to ‘over-reached’ or ‘over trained.’

Q. Tough training programmes are integral to sporting success, but what are the main problems that can occur if athletes over train?
We know that in the elite sport world, very small margins exist between defeat and victory. To succeed, an athlete must train extremely hard, and there are situations when a training programme requires an athlete, player or squad to be selectively overreached or overloaded for a short time period. With a subsequent, controlled reduction in training volume, a super-compensation occurs, allowing for a positive adaptation to the intense training dose and overall improved performance.

However, if athletes train too hard for too long in their pursuit of success, they will eventually fatigue and follow the performance continuum [Figure 1], which leads to injury and increased frequency of illness, such as upper-respiratory tract infections, immunosuppression, disturbed sleep patterns and depressed mood states. Biomarker analysis can help navigate the fine line required to balance adequate load with sufficient recovery.

Q. How did you establish which biomarkers were the most important for monitoring athletes in training and how do you carry out analysis of these biomarkers?
Our starting point is leveraging clinical markers that are routinely used for general health and wellness. In the context of training, we rely on biomarkers found in blood and saliva that are known signs of a normal process (e.g. adaptation), abnormal process (e.g. maladaptation), a particular condition (e.g. under performance syndrome) or disease (e.g. infection).

Biomarkers may be used to see how well the body responds to an intervention/process (e.g. training modification), a treatment (e.g. recovery solution) or a stress inducer (e.g. game, match). Our specialist team includes former speed and power coach to the New Zealand ‘All Blacks’ and Americas Cup sailing team, Dr Christian Cook; the first team physiologist to Real Madrid, Dr Carlos Gonzalez-Haro; the former Director of the Australian Institute of Sport Haematology Lab, Robin Parisotto; and Clinical and Performance Nutritionist to the British Olympic Team, Nathan Lewis (MSc). We have significant collective experience of applying, analysing and interpreting biomarkers across a range of elite sports at the very highest level of world competition. We facilitate analysis of markers that have been applied and validated in the world of elite sport. Our combined experience of working with thousands of elite athletes and monitoring them at key times during the season means we can discern trends that are consistent with either peak, or, at times, underperformance. We are especially interested in athletes’ cell counts, inflammatory markers, trace metal status, immunoglobulins and hormonal profiles.

Q. Are you satisfied with the methods and equipment used?
We are constantly looking for improvement and searching for markers that can give us objective information about an athlete’s response capabilities and/or status. For example, we utilise the routine parameters, including the differential WBC, haemoglobin and reticulocyte counts, available on the Siemens Healthcare Diagnostics ADVIA 2120 Haematology System, to give us rapid insights into an athlete’s health and wellness. We also rely on additional parameters available on this platform, such as the cellular haemoglobin of the reticulocyte (CHr) and the percentage hypochromasia of both the reticulocytes and mature red cells (%hypor and %hypom). These parameters are also routinely utilised in renal medicine to deliver specific information about the quality of erythropoiesis.

Historically, we would have used ferritin to assess the iron stores, but given the acute phase response of the parameter, we interpret the result in concert with the white cell counts and creatine kinase (CK), as we know the parameter is elevated in infection and inflammation. This information is especially important when an athlete is undertaking altitude or endurance training, as we can ensure enough iron is being made available to the developing red cells and they benefit from all their hard work. We can also pick up a functional or pre-latent iron deficiency before it impacts upon performance and track the responses to prescribed iron supplementation. Thus, in addition to looking for new techniques, we also seek to apply established principles in new ways.

Q. How do you see the future for sports medicine in general and ORRECO in particular?
As explained by our colleague, Dr Bruce Hamilton, sports medicine is no longer focused on just treating injury and illness in athletes. Increasingly, early recognition and prevention of injury and illness is the goal. Particularly when working with elite athletes, being able to identify athletes at risk of developing problems is a constant challenge, and vast amounts or research and resources are being directed at this task. Despite this, we are only just beginning to understand the risk factors behind even common injuries (e.g. hamstring muscle strains) and techniques that may be used to prevent them. Similarly, while illness and fatigue have been recognised as significant limitations to elite athletic performance for many years, to date, the understanding of risk factors and the ability to identify athletes at risk has been limited by both our knowledge base and our technical ability. The goal of tools, such as those developed by ORRECO, are to facilitate the identification and prevention of illness in highly tuned athletes, thereby allowing them to compete to the best of their ability. This is consistent with the aspirations of modern sports medicine around the world.

By integrating sports haematology and biochemistry with knowledge and expertise in clinical and performance nutrition, applied physiology, speed and power physiology, biostatistics and cellular nutrition across our team, whole avenues of possibility open up to performance science in general. ORRECO aims to provide a global resource for real-time sports haematology and biochemistry results for athletes training and competing around the world.

For more information go to www.orreco.com. An introductory video can be seen at http://vimeo.com/41485500.

Siemens Healthcare Diagnostics 

https://clinlabint.com/wp-content/uploads/sites/2/2020/08/Brian-Moore.jpg 349 300 3wmedia https://clinlabint.com/wp-content/uploads/sites/2/2020/06/clinlab-logo.png 3wmedia2020-08-26 09:47:292021-01-08 11:39:21Helping elite athletes to give a peak performance
25903 advert CLI oncology

BioVendor’s Range of Cancer Biomarkers

, 26 August 2020/in Featured Articles /by 3wmedia
https://clinlabint.com/wp-content/uploads/sites/2/2020/08/25903-advert_CLI_oncology.jpg 996 700 3wmedia https://clinlabint.com/wp-content/uploads/sites/2/2020/06/clinlab-logo.png 3wmedia2020-08-26 09:47:292021-01-08 11:39:35BioVendor’s Range of Cancer Biomarkers
BR1

Book review: Atlas of Genetic Diagnosis and Counseling. 2nd ed.

, 26 August 2020/in Featured Articles /by 3wmedia

by Harold Chen. Pub. by Springer 2012, 2472pp., €519. In 3 volumes, not available separately.
ISBN 978-1-4614-1036-2.

With almost 40 years of experience in clinical genetics, Dr Chen has shared his knowledge of almost 250 genetic disorders, malformations and malfunction syndromes. The author provides a detailed outline for each disorder, describing its genetics, basic defects, clinical features, diagnostic tests, and counselling issues, including recurrence risk, prenatal diagnosis, and management. Numerous colour photographs of prenatal ultrasounds, imagings, cytogenetics, and postmortem findings illustrate the clinical features of patients at different ages, patients with varying degrees of severity, and the optimal diagnostic strategies. The disorders cited are supplemented by case histories and diagnostic confirmation by cytogenetics, biochemical, and molecular techniques, when available. The Atlas of Genetic Diagnosis and Counseling will lead to a better understanding and recognition of genetic diseases and malformation syndromes as well as better evaluation, counselling and management of affected patients. In this new edition, 47 additional genetic disorders are added, as well as extensive updates made to the previous disorders. New illustrations, as previous edition, will be supplemented by case and family history, clinical features, and laboratory data, especially molecular confirmation.

SPRINGERwww.springer.com

https://clinlabint.com/wp-content/uploads/sites/2/2020/08/BR1.jpg 199 150 3wmedia https://clinlabint.com/wp-content/uploads/sites/2/2020/06/clinlab-logo.png 3wmedia2020-08-26 09:47:292021-01-08 11:39:15Book review: Atlas of Genetic Diagnosis and Counseling. 2nd ed.
25931 Pointe Sc

Manufacturer of Clinical Chemistry Reagents since 1981

, 26 August 2020/in Featured Articles /by 3wmedia
https://clinlabint.com/wp-content/uploads/sites/2/2020/08/25931-Pointe-Sc.jpg 994 692 3wmedia https://clinlabint.com/wp-content/uploads/sites/2/2020/06/clinlab-logo.png 3wmedia2020-08-26 09:47:292021-01-08 11:39:27Manufacturer of Clinical Chemistry Reagents since 1981
25854 BIP0282 BioPorto Annonce The NGAL Test CLI June issue 2012 92x178 PRESSREADY

The NGAL Test

, 26 August 2020/in Featured Articles /by 3wmedia
https://clinlabint.com/wp-content/uploads/sites/2/2020/08/25854-BIP0282-BioPorto-Annonce-The-NGAL-Test-CLI-June-issue-2012-92x178-PRESSREADY.jpg 1000 513 3wmedia https://clinlabint.com/wp-content/uploads/sites/2/2020/06/clinlab-logo.png 3wmedia2020-08-26 09:47:292021-01-08 11:39:29The NGAL Test
26059 Ani Labs CLI Sept 2012 Neo automate

All-in-One Automate for Neonatal Screening!

, 26 August 2020/in Featured Articles /by 3wmedia
https://clinlabint.com/wp-content/uploads/sites/2/2020/08/26059-Ani-Labs-CLI-Sept-2012-Neo-automate.jpg 320 700 3wmedia https://clinlabint.com/wp-content/uploads/sites/2/2020/06/clinlab-logo.png 3wmedia2020-08-26 09:47:292021-01-08 11:39:18All-in-One Automate for Neonatal Screening!
p24 01

Factors impacting on sample collection for urinary schistosomiasis research in Abeokuta, Nigeria

, 26 August 2020/in Featured Articles /by 3wmedia

Sample collection is an important aspect of scientific work because it shapes, to a great extent, the study design and methodology, both of which may influence the outcomes of scientific research. However, often in scientific evaluations of studies which involve both field sample collection and laboratory work, only the laboratory research aspect receives serious attention, while other factors such as the socio-cultural, ecological and belief values of subjects who donate samples for laboratory studies are much less emphasised. These factors and how they play out in any particular study area are critical determinants of successful field sample collection especially in the developing countries.
  
by Dr Olufunmilola Ibironke, Dr Samuel Asaolu and Dr Clive Shiff

Urinary schistosomiasis is caused by a trematode worm, Schistosoma haematobium [1]. Infection with this parasite has been shown to be the commonest cause of haematuria and urogenital diseases in endemic areas. Thus, detection of haematuria in urine has been proposed as a valid indicator of schistosome infection, and has been widely adopted in many national schistosomiasis control programmes [2,3]. Diagnostic procedures in control programmes accordingly involve collection of urine samples from patients.

Most studies of urinary schistosomiasis in Nigeria and other endemic countries have targeted schoolchildren [4-8], because they represent the prime reservoir for the parasite, and children are amenable to mass chemotherapy [9]. However, studies have shown the debilitating effect of the parasite among adults in communities where it is endemic [10-13] and so this population also needs to be studied. As opposed to urine sample collection from children which is mostly done in schools, collection of urine from adults is difficult, particularly among persons who do not consider schistosomiasis as their major health problem when compared to malaria. In a school-based setting, after obtaining clearance from government health and school administrative authorities, researchers usually work with school teachers to get permission from pupils’ parents, and to educate the children involved in the study about how to follow urine sample collection instructions. However, for studies which involve adults, researchers, with the help of local health officers, would have to deal with patients directly to seek their individual involvement in the study, the acceptance of which depends on a number of the above mentioned factors.

Few studies have investigated the sociology of communities involved in such studies. We present here a study on urinary schistosomiasis in two villages in Ogun State, Nigeria, involving collection of urine samples from adults, to investigate the factors that drive their acceptance or refusal for inclusion in the study.

Methods and study sites
The study involved adults between the ages of 20 and 55 years who were mobilised to school halls in each village through the respective heads of the villages. Participants were informed of their right to accept or reject inclusion in the study. Many adults refused to come to school halls, many others who came rejected inclusion in the study. Some others accepted inclusion and collected urine sample containers but never came back while others accepted full participation. People in endemic communities show negative attitudes to urine sample collection for different reasons. To find out villagers’ attitudes to the urine sample collection process, we asked consenting participants why their friends or family refused to participate and in the process we identified some factors responsible for their attitudes. We also visited some households either to seek consent for inclusion or to understand reasons for refusing inclusion in the study.

This study was conducted in July, 2010, in Ogun State, Nigeria as a part of a study on the diagnosis of urinary schistosomiasis in six villages. For the purpose of comparison, two villages, Apojola located in Odeda Local Government Area (LGA), and Ogbere in Ijebu-east LGA, were selected. Apojola is located on Oyan Dam Reservoir. The inhabitants are all immigrant fishermen and their families, and are a mixture of Moslem Hausas and Christian Idomas. Awawa River serves Ogbere community. The inhabitants are mainly Christian Yorubas, and a mixture of farmers and Local Government Area civil servants. Ethical consideration, the data collection process, the population of each village, vegetation types and locations of each local government area have been reported previously [14].

Observations and discussion
Socio-cultural aspect
Several urinary schistosomiasis studies had been conducted in Nigeria, most of which involved urine sample collection, so there is a high level of awareness about the importance of control programmes. However, in the process of field studies there is often confusion in the minds of the participants leading to fear of exposure to strangers which was found to prevail among the villagers. Frequently researchers are mistaken for government agents visiting for revenue collections. If the researcher can work with members of the community to change these opinions it would likely improve level of cooperation for inclusion in the study. We explored this aspect in Apojola, a community located on the heavily schistosome-infested Oyan dam reservoir. We made the first attempt to recruit participants through the community leader, followed by the religious leader, a nurse and a school teacher. The number of participants recruited through the assistance of the different leaders according to age and gender are shown in Table 1a. In Table 1b, it was shown that the community leader is the most effective in helping to mobilise the villagers of both genders for urine collection.

There is also an increasing cynicism about the disease among adult patients in endemic communities. Many members of the communities who admit passing blood in the urine do not perceive it as an indication of a serious disease. They consider it as a sign of virility and puberty which is a familiar sign among adults in other villages around them. A few others who have experienced some discomfort and thought it might be a major health problem were either ashamed of their disease status or ashamed of bringing their ‘red’ urine. Past studies have noted that individuals’ perceptions on the aetiology and impact of urinary schistosomiasis differed with their levels of education and gender [13]. Lack of knowledge about the cause and effect of the disease affects patient’s turnout for sample collection and this in turn has a direct influence on field data coverage and research quality.

Apart from lack of health education on the cause of the disease, the willingness to participate in the urine sample collection process is seemingly greater among patients with some level of education than among the uneducated. We investigated how patient’s level of education impacts turnout for urine sample collection in Ogbere community. Ogbere inhabitants are a mixture of uneducated farmers, who have nought to six years of formal education, and the educated comprising teachers and Local Government Area civil servants, who have from seven to 16 years of formal education. In Table 2, data from both groups are presented for comparison to show turnout according to education level and gender.

This Table shows the percentage contributions by the Community Leader (CL), Nurse (N), Teacher (T) and Religious Leader (RL) on the total number of respondents. CL is best for mobilising males in the community (P = 0.00155). CL is also best for mobilising male and female with calculated P = 0.052 just higher than 0.05. N is best for mobilising females but this is not statistically significant.

Ecological aspect
Transmission of urinary schistosomiasis is through freshwater snails, Bulinus species, as intermediate hosts and varies with different ecological factors. In many endemic communities, the ecological factors which favour disease transmission also promote agricultural practices such as farming, cattle rearing and fishing. Therefore, transmission to humans often occurs as a result of irrigation systems for agricultural purposes or when visits are made to the rivers for washing and swimming. As such, the rate of transmission to humans varies, to a great extent, with occupation.
However, since diagnosis is by urine testing, many peasant farmers and fishermen who are thought to be the most impacted with S. haematobium because of frequent water contact may remain undiagnosed and untreated. Urine sample collection for the diagnosis of urinary schistosomiasis is preferably done between the hours of 10:00 and 14:00 for optimum egg passage [9]. These hours coincide with the time during which farmers go to farm and fishermen set nets for fish catching. This coincidence might affect turnout for sample collection and estimation of overall disease prevalence in the community.

To evaluate the impact of patient’s occupation on turnout for urine sample collection, we compared turnout of farmers and civil servants in Ogbere community. For statistical purpose, farmers, cattle rearers and fishermen are classified as farming, while students, teachers and local government workers are classified as civil servants, see Table 2. In total, there are 84 participants out of which 33 are farmers (39.2%) and 51 are civil servants (60.7%). In all, more women (79.8%) turned out for sample collection.

According to the community leader, the total adults’ population in Ogbere is 3121 and the ratio of farmers to civil servants is approximately 20:1.

Z- Distribution test was used to compare the response level between the two groups using the formula:

(see picture number 4)

where p is the difference of proportions, N1 = 149 = Educated population and N2 = 2972 = Uneducated population. At all levels of significance 0.05, 0.01 and 0.001, response from the educated civil servant population was significantly higher than response from the uneducated farmer population.

Belief structures
Christians in Apojola and Ogbere communities were relatively unhindered by religious belief regarding their willingness to come forward for education about the project and provision of their urine samples. However there was gender problem with urine collection among the Muslim families at Apojola. The Muslim families at Apojola have the culture of restricting married women within the family household compounds and forbiding male visitors of adolescent age and older from entering the compounds or visiting the women. In order to be able to collect urine samples from these Muslim women, the local community nurse and a female member of our research team were accompanied by a local female Muslim field assistant and interpreter before being allowed access to the compounds to explain the importance of the disease and purpose of the study.

Conclusion
This study attempts to find out patients‘ attitudes to scientific research especially during a field sample collection process and suggests possible reasons for rejection of inclusion in scientific research by patients. In general, this study showed that social and ecological values including educational background, occupation, religious practices and poor knowledge about the aims and objectives of the study, strongly influence turnout for urine sample collection. Therefore, such values are worth considering for a holistic understanding of the scientific study results.

References
1. Edungbola LD, Asaolu SO, Omonisi MK, Aiyedun BA. Schistosoma haematobium infection among schoolchildren in the Babana district, Kwara State, Nigeria. Afr J Med Sci 1988; 7: 187-193.
2. Koukounari A, Gabrielli AF, Toure S, Bosque-Oliva E, Zhang Y, Sellin B, Donnelly CA, Fenwick A, Webster JP. Schistosoma haematobium infection and morbidity before and after large-scale administration of praziquantel in Burkina Faso. J Infect Dis 2007; 196: 659-669.
3. Webster JP, Koukounari A, Lamberton PH, Stothard JR, Fenwick A. Evaluation and application of potential schistosome-associated morbidity markers within large-scale mass chemotherapy programmes. Parasitology 2009; 136: 1789-1799.
4. Abdel-Wahab MF, Esmat G, Ramzy I, Fouad R, Abdel-Rahman M, Yosery A, Narooz S, Strickland GT. Schistosoma haematobium infection in Egyptian schoolchildren: demonstration of both hepatic and urinary tract morbidity by ultrasonography. Trans R Soc Trop Med Hyg 1992; 86: 406-409.
5. Fenwick A, Webster JP, Bosque-Oliva E, Blair L, Fleming FM, Zhang Y, Garba A, Stothard JR, Gabrielli AF, Clements AC, Kabatereine NB, Toure S, Dembele R, Nyandindi U, Mwansa J et al. The Schistosomiasis Control Initiative (SCI): rationale, development and implementation from 2002-2008. Parasitology 2009; 136: 1719-1730.
6. French MD, Rollinson D, Basanez MG, Mgeni AF, Khamis IS, Stothard JR. School-based control of urinary schistosomiasis on Zanzibar, Tanzania: monitoring micro-haematuria with reagent strips as a rapid urological assessment. J Pediatr Urol 2007; 3: 364-368.
7. Nduka FO, Ajaero CM, Nwoke BE. Urinary schistosomiasis among school children in an endemic community in south-eastern Nigeria. Appl Parasitol 1995; 36: 34-40.
8. Okoli EI, Odaibo AB. Urinary schistosomiasis among schoolchildren in Ibadan, an urban community in south-western Nigeria. Trop Med Int Health 1999; 4: 308-315.
9. Ibironke OA, Phillips AE, Garba A, Lamine SM, Shiff C. Diagnosis of Schistosoma haematobium by detection of specific DNA fragments from filtered urine samples. Am J Trop Med Hyg 2011; 84: 998-1001.
10. Koukounari A, Webster JP, Donnelly CA, Bray BC, Naples J, Bosompem K, Shiff C. Sensitivities and specificities of diagnostic tests and infection prevalence of Schistosoma haematobium estimated from data on adults in villages northwest of Accra, Ghana. Am J Trop Med Hyg 2009; 80: 435-441.
11. Mostafa MH, Sheweita SA, O’Connor PJ. Relationship between schistosomiasis and bladder cancer. Clin Microbiol Rev 1999; 12: 97-111.
12. Mungadi IA,.Malami SA. Urinary bladder cancer and schistosomiasis in North-Western Nigeria. West Afr J Med 2007; 26: 226-229.
13. Sarkinfada F, Oyebanji AA, Sadiq IA, Ilyasu Z. Urinary schistosomiasis in the Danjarima community in Kano, Nigeria. J Infect Dev Ctries 2009; 3: 452-457.
14. Ibironke O, Koukounari A, Asaolu S, Moustaki I, Shiff C. Validation of a new test for Schistosoma haematobium based on detection of Dra1 DNA fragments in urine: evaluation through latent class analysis. PLoS Negl Trop Dis 2012; 6: e1464.

The authors
Dr Olufunmiola Ibironke*
Cell and DNA Repository
Rutgers, The State University of New Jersey
New Brunswick
New Jersey, USA
e-mail: oai5@rutgers.edu

Dr Clive Shiff
Department of Molecular Microbiology and Immunology
Johns Hopkins Bloomberg School of Public Health
Baltimore, MD, USA
e-mail: cshiff@jhsph.edu

Dr Samuel Asaolu
Department of Zoology
Obafemi Awolowo University
Ile-Ife
Nigeria

*Corresponding author

https://clinlabint.com/wp-content/uploads/sites/2/2020/08/p24_01.jpg 344 500 3wmedia https://clinlabint.com/wp-content/uploads/sites/2/2020/06/clinlab-logo.png 3wmedia2020-08-26 09:47:292021-01-08 11:39:31Factors impacting on sample collection for urinary schistosomiasis research in Abeokuta, Nigeria
25857 CLI jun 2012

We improve the well-being of people around the world

, 26 August 2020/in Featured Articles /by 3wmedia
https://clinlabint.com/wp-content/uploads/sites/2/2020/08/25857_CLI-jun-2012.jpg 1000 682 3wmedia https://clinlabint.com/wp-content/uploads/sites/2/2020/06/clinlab-logo.png 3wmedia2020-08-26 09:47:292021-01-08 11:39:29We improve the well-being of people around the world
26094 AST 001 ad for CLI oc

Diagnostics for personalised medicine

, 26 August 2020/in Featured Articles /by 3wmedia
https://clinlabint.com/wp-content/uploads/sites/2/2020/08/26094-AST-001-ad-for-CLI-oc.jpg 1000 686 3wmedia https://clinlabint.com/wp-content/uploads/sites/2/2020/06/clinlab-logo.png 3wmedia2020-08-26 09:47:292021-01-08 11:39:11Diagnostics for personalised medicine

Biomarkers in the management of cardiorenal syndrome

, 26 August 2020/in Featured Articles /by 3wmedia

The cardiorenal syndrome (CRS) involves both kidney failure and heart failure, with the failing organ initially being either the heart or the kidney; usually one failing organ leads to the failure of the other. While use of biomarkers and imaging techniques can assess cardiovascular function, the assessment of renal injury and function is complex in CRS patients. This article discusses some of the novel markers for the assessment of renal function and injury.

Renal dysfunction is an independent and significant contributor to poor heart failure outcomes. Serum creatinine (SCr), the most frequently used marker for clinical assessment of renal dysfunction and injury, is at best a retrospective window. Glomerular filtration rate, GFR, considered the best overall measure of renal function (RF), is similarly affected by multiple variables, but novel biomarkers of renal injury and function are now available. These biomarkers also have limitations but they address gaps in the information provided from use of conventional biomarkers

A marker of renal function: cystatin-C
Cystatin C, an endogenous proteinase inhibitor of low molecular weight (13-kDa), possesses many features that make it attractive as a surrogate marker of RF and GFR. It is synthesised and released into plasma by all nucleated cells at a constant rate, is freely filtered by the glomerulus and completely reabsorbed by the proximal tubules. It can be easily measured in the serum and plasma without the need for a urine sample or complex equations. It is not affected by changes in body mass, nutrition, age or gender, making it potentially more beneficial in critically ill patients, elderly and children. It has been validated as a marker of GFR in patients with pre-existing renal dysfunction and acute kidney injury (AKI) as levels increase before SCr. In congestive heart failure (CHF) Cys-C is superior to SCr based estimates, which underestimate GFR. This appears to extend to acure decompensated heart failure (ADHF) admissions without advanced RF. Cys-C also reflects myocardial stress and damage, reflects more advanced left ventricular diastolic and right ventricular systolic dysfunction and is an independent predictor of long-term prognosis after adjusting for myocardial factors. The advantage of Cys-C over SCr appears greater and more conclusive for ruling in renal injury in affected patients. Other benefits include predicting future CV events in intermediate-risk individuals, mainly through the identification of those unlikely to develop events; it is a stronger predictor of adverse events than conventional measurement of RF and, in combination with cardiac troponin T and N-terminal–pro-brain natriuretic peptide, it improves risk stratification for CV mortality (inclusive of HF) beyond models of established risk factors.

Novel assessments of renal injury
The potential to attenuate or reverse renal injury is far less likely when renal dysfunction is already evident, at least based on current assessment methods. Several promising AKI biomarkers arenow available.

Neutrophil gelatinase-associated lipocalin
Human neutrophil gelatinase-associated lipocalin (NGAL) is a 25-kDa protein initially described to be bound to gelatinase in specific granules of the neutrophil, with recent evidence suggesting physiological activity in the kidney. It is expressed and secreted by immune cells, hepatocytes and renal tubular cells in various pathologic states. NGAL exerts bacteriostatic effects, which are explained by its ability to capture and deplete siderophores, small iron-binding molecules that are synthesised by certain bacteria as a means of iron acquisition and role in cell survival, inflammation and matrix degradation. NGAL is up regulated more than 10-fold in post ischaemic renal injury in a mouse model and secreted relatively early into the urine. Several recent studies in homogenous (adult and paediatric cardiac surgery), heterogeneous (intensive care and emergency department) and chronic kidney disease (CKD) populations have supported the use of NGAL as an important biomarker in early diagnosis and prediction of duration and severity of AKI. NGAL differentiates AKI from changes in GFR due to chronic disease progression, predicts duration of ICU stay and provides prognostic value. Specifically, a single urine level of NGAL in the emergency department differentiates AKI from normal function and from pre-renal azotaemia, and predicts poor in-patient outcome.

A recent multicentre pooled analysis of published data on 2322 critically ill children and adults with the cardiorenal syndrome revealed the surprising finding that approximately 20% of patients display early elevations in NGAL concentrations but never develop increases in serum creatinine. Importantly, this sub-group of ‘NGAL-positive creatinine-negative’ subjects encountered a substantial increase in adverse clinical outcomes, including mortality, dialysis requirement, ICU stay and overall hospital stay. Thus, early NGAL measurements can identify patients with sub-clinical AKI who have an increased risk of adverse outcomes, even in the absence of diagnostic increases in serum creatinine.

Among acute decompensated heart failure patients, high admission serum NGAL levels were associated with increased risk of worsening RF. In particular, patients with an NGAL of >140 ng/mL on admission had a 7.4-fold increased risk, with a sensitivity and specificity of 86% and 54%, respectively. NGAL values are also significantly increased and parallel the clinical severity of CHF. After a 2-year follow up, patients with baseline NGAL > 783 ng/mL had a significantly higher mortality. These findings may suggest that NGAL plays a pivotal role in the systemic adaptation to CHF. Elevated baseline serum levels in acute post-myocardial infarction and CHF correlated with clinical and neurohormonal deterioration and adverse outcomes. In a rat model of post-MI HF, NGAL/lipocalin-2 gene expression was increased in the non-ischaemic left ventricle segments, primarily located to cardiomyocytes. Strong NGAL immunostaining was found within cardiomyoctes in experimental and clinical HF. Furthermore interleukin-1β and agonists for toll-like receptors 2 and 4 were potent inducers of NGAL/lipocalin-2 in isolated neonatal cardiomyocytes supporting a role for the innate immune system in HF pathogensesis. Urinary NGAL also increases in parallel with the NYHA classes for HF and is also closely correlated with serum NGAL, Cys-C, SCr and eGFR. This suggests tubular damage may accompany renal dysfunction in CHF, which has prognostic consequences.

Evidence is continuing to accumulate and NGAL measurement appears to be of diagnostic and prognostic value. In a recent meta-analysis, NGAL levels predicted renal replacement therapy initiation and in-hospital mortality. Several recent studies showing the response of urinary levels to therapy suggest a future role for NGAL for follow up and monitoring the status and treatment of diverse renal diseases reflecting defects in the glomerular filtration barrier, proximal tubule reabsorption and distal nephrons. Thus the prospects of NGAL being used as a diagnostic tool, even beyond the realms of nephrology, are exciting but require further clinical research. The commercial availability of standardised clinical platforms for the accurate and rapid measurement of NGAL in the urine and plasma will facilitate future investigations as well as direct clinical applications.

Interleukin-18
Interleukin (IL)-18 is a proinflammatory cytokine which induces interferon-g production in T cells and natural killer cells. It is synthesised as a biologically inactive precursor, which requires cleavage into an active molecule by an intracellular cysteine protease similar to IL-1b. IL-18 is both a mediator and biomarker of ischaemic AKI. Several early studies demonstrate increases in patients with acute tubular necrosis, prerenal azotaemia, nephrotic syndrome, delayed graft function after renal transplantation, chronic renal insufficiency and urinary tract infections. In contrast nephropathy, cardiopulmonary bypass, critically ill children and kidney transplantation, urinary IL-18 rises two days earlier than SCr. Urine IL-18 increases four to six hours after cardiopulmonary bypass, peaks at over 25-fold at 12 hours, and remains elevated up to 48 hours later. IL-18 levels also predict graft recovery and need for dialysis up to three months later. There is also significant evidence that IL-18 contributes to clinical HF and other acute and chronic cardiovascular presentations. Presently there are no studies with patients with CRS.

Major concerns over IL-18 surround its discriminatory capacity and appropriate use. One concern is a spill over into the urine and its effects as a confounder, differentiating elevated cardiac as opposed to renal injury. Additionally, serum IL-18 may be increased in other disease states e.g. autoimmune disorders such as SLE, certain leukaemias, postoperative sepsis, chronic liver disease and acute coronary syndromes. On a positive note serum IL-18 levels were not different between those with and without AKI post paediatric cardiac surgery, and data suggesting its pathophysiological contribution to the renal damage observed during ischaemia/reperfusion are positive signs for its discriminatory values and causative effects in renal injury. Thus IL-18 appears to be a worthwhile addition to a biomarker panel in the assessment of AKI.

Kidney injury molecule-1
Kidney injury molecule-1 (KIM-1) is a transmembrane protein that is highly over expressed in proximal tubule cells after ischaemic or nephrotoxic AKI. Several studies have shown KIM-1 in urine and renal biopsy to be elevated from predominately ischaemic AKI and not from prerenal azotaemia, chronic renal disease, and contrast nephropathy. KIM-1 appears to play a role in the pathogenesis of tubular cell damage and repair in experimental and human kidney disease. KIM-1 is a sensitive marker for the presence of tubular damage. It is virtually undetectable in healthy kidney tissue, but tubular KIM-1 expression is strongly induced in acute and chronic kidney disease as well as transplant dysfunction, where it is significantly associated with tubulointerstitial damage and inflammation. Elevated urinary KIM-1 levels are strongly related to tubular KIM-1 expression in experimental and human renal disease, indicating that urinary KIM-1 is a very promising biomarker for the presence of tubulo-interstitial pathology and damage. Furthermore, urinary excretion of KIM-1 is an independent predictor of graft loss in renal transplant recipients, demonstrating its prognostic impact. Studies after cardiopulmonary bypass surgery have noted similar findings. KIM-1 also predicts adverse clinical outcomes in various forms of AKI. Data from non-diabetic proteinuric patients suggest that urinary excretion of KIM-1 may have the potential to guide renoprotective intervention therapy. KIM-1 could potentially provide additional prognostic data for tubular damage in CHF. Future studies will reveal whether the sensitive biomarker KIM-1 will become a therapeutic target itself. Kim-1/KIM-1 dipsticks can provide sensitive and accurate detection of Kim-1/KIM-1, thereby providing a rapid diagnostic assay for kidney damage and facilitating the rapid and early detection of kidney injury in preclinical and clinical studies. The primary limitation of KIM-1 is that time to peak is 12 to 24 hours after insult. While it may be of limited use as an early AKI biomarker, the ability to detect KIM-1 in urine makes it an attractive option, possibly in a biomarker panel togther with NGAL and IL-18.

L-FABP
The fatty acid-binding proteins (FABPs) are 15kDa cytoplasmic proteins. There are two types: heart type (H-FABP) located in the distal tubular cells and liver type (L-FABP) which is expressed in the proximal tubular cells. Both markers have been suggested as useful for the rapid detection and monitoring of renal injury. H-FABP has been tested as a marker for ischaemic injury in donor kidneys. L-FABP has been tested in progressive ESRD as well as renal injury post renal transplantation and cardiopulmonary bypass and more recently acute coronary syndromes. In patients undergoing PCI for unstable angina, urine L-FABP levels were significantly elevated after two and four hours and remained elevated for 48 hours. SCr did not change significantly during the study period. Among nondiabetic CKD patients, urine L-FABP levels correlated with urine protein and SCr levels. Notably, L-FABP levels were significantly higher in patients with mild CKD who progressed to more severe disease. Neither SCr nor urine protein differed between those same groups. H-FABP however is produced by myocardial damage and its clearance is determined by RF. The ratio of H-FABP to myoglobin after haemodialysis may be a useful marker for estimating cardiac damage and volume overload in haemodialysis. This may be an advantage for FABP in a panel of biomarkers to discrimnate background noise and cases where troponin levels can’t be interpreted. The main drawbacks are lack of evidence in the HF setting, small sample sizes in existing studies, and non-availability of a commercially usable assay. Additional longitudinal studies are needed to demonstrate the ability of L-FABP to predict AKI as well as CKD and its progression in cohorts with CKD of multiple aetiologies.

Biomarker panels
Each of these biomarkers has advantages and limitations. It will be a while yet before any of these biomarkers match serum troponin and act as a ‘standalone’ marker. However they do provide a safety mechanism initially to highlight anticipated risk, as well as additional information on likely renal pathophysiology. It may ultimately be that a panel of biomarkers is required. Candidates for inclusion are NGAL, IL-18, KIM-1, Cys C and L-FABP. The alternative may be selective use of markers when renal injury is anticipated, a strategy synonymous with acute coronary syndromes with serial cardiac enzymes, i.e.’serial renal enzymes’. Ultimately a point of care device would be ideal, and some kits are already in place. It is however clear that the learning paradigm is still ongoing. Future studies will need to validate these biomarker panels in a large heterogenous cohort.

The future of renal assessments in cardiovascular patients
Renal dysfunction is an independent and significant contributor to poor heart failure outcomes. Idiosyncracies in cardiorenal physiology and limitations of conventional diagnostic tools are factors in the poor prescribing of proven heart failure therapies in these patients. Novel biomarkers of renal injury and function are currently available. These biomarkers do have limitations but they address gaps in the information gained from conventional biomarkers i.e. improvements in injury chronology and functional accuracy. Significant limitations in how these markers are used as well as issues of availability and cost can only be addressed by further work. Future research studies should consider addressing these questions.

Reference
Abstracted with permission from Iyngkaran P et al. Cardiorenal syndrome – definition, classification and new perspective in diagnostics. Seminars in Nephrology 2012; 32: 3-17.

https://clinlabint.com/wp-content/uploads/sites/2/2020/06/clinlab-logo.png 0 0 3wmedia https://clinlabint.com/wp-content/uploads/sites/2/2020/06/clinlab-logo.png 3wmedia2020-08-26 09:47:292021-01-08 11:39:21Biomarkers in the management of cardiorenal syndrome
Page 36 of 145«‹3435363738›»
Bio-Rad - Preparing for a Stress-free QC Audit

Latest issue of Clinical laboratory

March 2026

CLi Cover MRCH 2026
11 March 2026

Isomorphic Labs unveils IsoDDE, a unified AI drug design engine surpassing AlphaFold 3 in biomolecular prediction

11 March 2026

Androgen testing for PCOS diagnosis

9 March 2026

DiaSys Diagnostic Systems | ACE FS

Digital edition
All articles Archived issues

Free subscription

View more product news

Get our e-alert

The leading international magazine for Clinical laboratory Equipment for everyone in the Vitro diagnostics

Sign up today
  • News
    • Featured Articles
    • Product News
    • E-News
  • Magazine
    • About us
    • Archived issues
    • Free subscriptions
    • Media kit
    • Submit Press Release
clinlab logo blackbg 1

Prins Hendrikstraat 1
5611HH Eindhoven
The Netherlands
info@clinlabint.com

PanGlobal Media is not responsible for any error or omission that might occur in the electronic display of product or company data.

Scroll to top

This site uses cookies. By continuing to browse the site, you are agreeing to our use of cookies.

Accept settingsHide notification onlyCookie settings

Cookie and Privacy Settings



How we use cookies

We may ask you to place cookies on your device. We use cookies to let us know when you visit our websites, how you interact with us, to enrich your user experience and to customise your relationship with our website.

Click on the different sections for more information. You can also change some of your preferences. Please note that blocking some types of cookies may affect your experience on our websites and the services we can provide.

Essential Website Cookies

These cookies are strictly necessary to provide you with services available through our website and to use some of its features.

Because these cookies are strictly necessary to provide the website, refusing them will affect the functioning of our site. You can always block or delete cookies by changing your browser settings and block all cookies on this website forcibly. But this will always ask you to accept/refuse cookies when you visit our site again.

We fully respect if you want to refuse cookies, but to avoid asking you each time again to kindly allow us to store a cookie for that purpose. You are always free to unsubscribe or other cookies to get a better experience. If you refuse cookies, we will delete all cookies set in our domain.

We provide you with a list of cookies stored on your computer in our domain, so that you can check what we have stored. For security reasons, we cannot display or modify cookies from other domains. You can check these in your browser's security settings.

.

Google Analytics Cookies

These cookies collect information that is used in aggregate form to help us understand how our website is used or how effective our marketing campaigns are, or to help us customise our website and application for you to improve your experience.

If you do not want us to track your visit to our site, you can disable this in your browser here:

.

Other external services

We also use various external services such as Google Webfonts, Google Maps and external video providers. Since these providers may collect personal data such as your IP address, you can block them here. Please note that this may significantly reduce the functionality and appearance of our site. Changes will only be effective once you reload the page

Google Webfont Settings:

Google Maps Settings:

Google reCaptcha settings:

Vimeo and Youtube videos embedding:

.

Privacy Beleid

U kunt meer lezen over onze cookies en privacy-instellingen op onze Privacybeleid-pagina.

Privacy policy
Accept settingsHide notification only

Subscribe now!

Become a reader.

Free subscription