Clin Biochem Rev [journal]
- Fat-Soluble Vitamins: Clinical Indications and Current Challenges for Chromatographic Measurement. [Journal Article, Review]
- Clin Biochem Rev 2016 Feb; 37(1):27-47.
Fat-soluble vitamins, including vitamins A, D and E, are required for a wide variety of physiological functions. Over the past two decades, deficiencies of these vitamins have been associated with increased risk of cancer, type II diabetes mellitus and a number of immune system disorders. In addition, there is increasing evidence of interactions between these vitamins, especially between vitamins A and D. As a result of this enhanced clinical association with disease, translational clinical research and laboratory requests for vitamin measurements have significantly increased. These laboratory requests include measurement of 25-OHD (vitamin D), retinol (vitamin A) and α-tocopherol (vitamin E); the most accepted blood indicators for the assessment of body fat-soluble vitamin (FSV) status. There are significant obstacles to precise FSV measurement in blood. These obstacles include their physical and chemical properties, incomplete standardisation of measurement and limitations in the techniques that are currently used for quantification. The aim of this review is to briefly outline the metabolism and interactions of FSV as a prelude to identifying the current challenges for the quantification of blood vitamins A, D and E.
- An Age-Calibrated Definition of Chronic Kidney Disease: Rationale and Benefits. [Journal Article]
- Clin Biochem Rev 2016 Feb; 37(1):17-26.
Defining chronic kidney disease (CKD) is the subject of intense debate in the current nephrology literature. The debate concerns the threshold value of estimated glomerular filtration rate (eGFR) used to make the diagnosis of CKD. Current recommendations argue that a universal threshold of 60 mL/min/1.73m(2) should be used. This threshold has been defended by epidemiological studies showing that the risk of mortality or end-stage renal disease increases with an eGFR below 60 mL/min/1.73m(2). However, a universal threshold does not take into account the physiologic decline in GFR with ageing nor does it account for the risk of mortality and end-stage renal disease being trivial with isolated eGFR levels just below 60 mL/min/1.73m(2) in older subjects and significantly increased with eGFR levels just above 60 mL/min/1.73m(2) among younger patients. Overestimation of the CKD prevalence in the elderly (medicalisation of senescence) and underestimation of CKD (potentially from treatable primary nephrologic diseases) in younger patients is of primary concern. An age-calibrated definition of CKD has been proposed to distinguish age-related from disease-related changes in eGFR. For patients younger than 40 years, CKD is defined by eGFR below 75 mL/min/1.73m(2). For patients with ages between 40 and 65 years, CKD is defined by 60 mL/min/1.73m(2). For subjects older than 65 years without albuminuria or proteinuria, CKD is defined by eGFR below 45 mL/min/1.73m(2).
- Androgen Receptor Structure, Function and Biology: From Bench to Bedside. [Journal Article, Review]
- Clin Biochem Rev 2016 Feb; 37(1):3-15.
The actions of androgens such as testosterone and dihydrotestosterone are mediated via the androgen receptor (AR), a ligand-dependent nuclear transcription factor and member of the steroid hormone nuclear receptor family. Given its widespread expression in many cells and tissues, the AR has a diverse range of biological actions including important roles in the development and maintenance of the reproductive, musculoskeletal, cardiovascular, immune, neural and haemopoietic systems. AR signalling may also be involved in the development of tumours in the prostate, bladder, liver, kidney and lung. Androgens can exert their actions via the AR in a DNA binding-dependent manner to regulate target gene transcription, or in a non-DNA binding-dependent manner to initiate rapid, cellular events such as the phosphorylation of 2(nd) messenger signalling cascades. More recently, ligand-independent actions of the AR have also been identified. Given the large volume of studies relating to androgens and the AR, this review is not intended as an extensive review of all studies investigating the AR, but rather as an overview of the structure, function, signalling pathways and biology of the AR as well as its important role in clinical medicine, with emphasis on recent developments in this field.
- Variation in Laboratory Reporting of Haemolysis - a Need for Harmonisation. [Journal Article]
- Clin Biochem Rev 2015 Nov; 36(4):133-7.
The purpose of this survey was to determine the cut-offs being used by Australian laboratories using their instrument's Haemolysis Index (HI), whether these cut-offs vary, and at what level of haemolysis (or haemolysis index) did laboratories stop reporting one or more analytes. This was done in response to the large numbers of haemolysed samples reported in the RCPAQAP Key Incident Monitoring and Management System External Quality Assurance program (KIMMS EQA) and lack of information in the literature at the time regarding what to do once a haemolysed sample was identified. As it was known from discussions with laboratory personnel that different instruments reported their HI differently, we asked for the results to be provided in g/L free haemoglobin.An electronic survey was conducted with participants enrolled in the RCPA Quality Assurance Programs with a total of 68 laboratories responding to this survey. Some questions attracted a lower level of response.The responses showed a poor understanding of the relationship between HI units and haemoglobin concentration. There was wide variation in the way HI results were reported and thus comparing cut-off values for reporting specific analytes based on the HI was impossible to determine.There is a need to harmonise the way laboratories report analytes in the presence of haemolysis. This would involve adopting a uniform definition of HI and a protocol for laboratories to confirm for themselves the level of HI at which each analyte is no longer reported, as this is method dependent and so will vary from laboratory to laboratory.
- Aspects to Consider in Adopting Pregnancy-Specific Reference Intervals. [Journal Article]
- Clin Biochem Rev 2015 Nov; 36(4):127-32.
- Reporting Thyroid Function Tests in Pregnancy. [Journal Article, Review]
- Clin Biochem Rev 2015 Nov; 36(4):109-26.
While there is agreement that overt maternal hypothyroidism (serum thyroid stimulating hormone (TSH) >10 mIU/L) should be treated immediately, the evidence is mixed regarding the harm associated with subclinical hypothyroidism and the benefits of thyroxine replacement. The diagnosis of subclinical hypothyroidism rests on the recognition of an increased serum concentration of TSH which may be affected by many factors including gestational age, analytical method, the antibody status of the mother, ethnicity, iodine nutrition and even the time of day when the blood is collected. The 97.5(th) percentile of TSH at the end of the first trimester is commonly used as the upper boundary of normal in early pregnancy with a default value of 2.5 mIU/L specified in a number of recent clinical guidelines. There have now been numerous papers showing that a more realistic figure is between 3.0 and 4.0 mIU/L depending on the analytical method that is used. There are suggestions that ethnicity may also have a significant effect on TSH and FT4 reference limits in pregnancy.
- Consensus Statement for the Management and Communication of High Risk Laboratory Results. [Journal Article, Review]
- Clin Biochem Rev 2015 Aug; 36(3):97-105.
Ineffective test follow-up is a major source of harm for patients around the world. Unreliable communication from medical laboratories (henceforth termed 'laboratories') to clinicians of results that represent critical or significant risk to patients (collectively termed 'high risk results') is a contributing factor to this problem. Throughout Australasia, management practices for such results vary considerably. The recommendations presented in this document are based on best practice derived from the published literature and follow consultation with a wide range of stakeholders. These recommendations were created to harmonise Australasian practices by guiding laboratories in the design and implementation of safe and effective communication procedures for managing high risk results which require timely notification.
- Adventures with Creatinine and eGFR - A National, International and Personal Story - AACB Roman Lecture 2014. [Journal Article]
- Clin Biochem Rev 2015 May; 36(2):75-82.
In Australia and New Zealand today there is a commonality in all laboratories in many areas of testing related to Chronic Kidney Disease (CKD). These include creatinine assay standardisation, estimated Glomerular Filtration Rate (eGFR) reporting and the use of common units for serum creatinine and eGFR. This is supported by a single definition for diagnosis and staging of CKD, agreed indications for who and how to test together with detailed advice on test interpretation and patient management provided by our nephrology colleagues. These outcomes are the product of a decade of effort within Australia and New Zealand with collaboration between clinical disciplines and amongst laboratories. These local activities have been based on and supported by international actions in assay standardisation, eGFR formula development, understanding of clinical outcomes and guideline development. It is my belief that the local implementation of the current laboratory-based CKD testing processes is an outstanding example of good laboratory practice. This paper outlines the local and international activities and provides a view of my personal adventures with creatinine and eGFR.
- Regional Variation in Analytical Techniques used in the Diagnosis and Monitoring of Porphyria: a Case for Harmonisation? [Journal Article]
- Clin Biochem Rev 2015 May; 36(2):63-74.
The Royal College of Pathologists of Australasia (RCPA) Porphyrin Quality Assurance Program assesses the measurement of urine, faecal, plasma and whole blood porphyrins and their components plus urinary porphobilinogen and delta aminolaevulinic acid and has laboratories enrolled from around the world. It was observed that there was a wide scatter in results submitted to some subsections of the program.A detailed questionnaire covering the analytical techniques used in the diagnosis of porphyria was sent to all laboratories enrolled in the RCPA Porphyrin Quality Assurance Program. Additionally, self-enrolment data over a five year period was examined for trends/changes in standardisation, reagent sources and analytical technique.Twenty of the 45 laboratories enrolled in the Porphyrin Quality Assurance Program completed the survey, providing a snapshot of the analytical techniques used world-wide. Post survey self enrolment data indicated only little or no noticeable changes to analytical standardisation of techniques despite the continual lack of agreement of results in subsections of the External Quality Assurance program.While some aspects of porphyria testing are relatively consistent between laboratories, other diagnostic techniques vary widely. A wide variety of individualised reference intervals and reporting techniques is currently in use world-wide. While most of the participants in the survey are regional reference centres specialising in the diagnosis of porphyria and, as such, their diagnostic capability is not in question, international guidelines or global harmonisation of analytical techniques should allow better inter-laboratory comparisons to be made, ultimately improving diagnostic accuracy.