Annals of Clinical Biochemistry: International Journal of Laboratory Medicine

Acute kidney injury is a common complication of acute illnesses and is associated with increased morbidity and mortality. Over the past years several acute kidney injury biomarkers for diagnostication, decision-making processes, and prognosis of acute kidney injury and its outcomes have been developed and validated. Among these biomarkers, tissue inhibitor of metalloproteinase-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7), the so-called cell cycle arrest biomarkers, showed a superior profile of accuracy and stability even in patients with substantial comorbidities. Therefore, in 2014, the US Food and Drug Administration approved the use of the product of TIMP-2 and IGFBP7 ([TIMP-2] × [IGFBP7]), known as cell cycle arrest biomarkers, to aid critical care physicians and nephrologists in the early prediction of acute kidney injury in the critical care setting. To date, Nephrocheck® is the only commercially available test for [TIMP-2] × [IGFBP7]. In this narrative review, we describe the growing clinical and investigational momentum of biomarkers, focusing on [TIMP-2] × [IGFBP7], as one of the most promising candidate biomarkers. Additionally, we review the current state of clinical implementation of Nephrocheck®.

Lipoprotein(a) has long been regarded as a risk factor for cardiovascular disease; however, its routine use in clinical practice has been hampered by difficulties inherent in the measurement of this complex lipoprotein. The major challenges relate to its size heterogeneity and related issues including (1) use of appropriate calibrators (2) standardization of calibration protocols (3) traceability and (4) reporting units. In the UK, results from the current EQA schemes for lipoprotein(a) suggest that there is considerable work required to standardize lipoprotein(a) measurement. This is becoming increasingly pertinent with the increasing recognition of lipoprotein(a) as an independent risk factor for cardiovascular disease in international guidelines and the emergence of novel antisense therapies to effectively reduce lipoprotein(a). This article raises awareness of the importance of measurement of lipoprotein(a) for the assessment of cardiovascular disease risk and gives guidance to clinical laboratories regarding choice of appropriate assays.

Chronic diarrhoea is common and mostly due to diarrhoea predominant irritable bowel syndrome. Diarrhoea predominant irritable bowel syndrome affects about 11% of the population; however, up to a third of these patients actually have bile acid diarrhoea. There are, therefore, more than one million sufferers of bile acid diarrhoea in the UK. Bile acid diarrhoea is caused by small bowel malabsorption of bile acids and the increased bile acids in the large intestine cause diarrhoea. Once diagnosed, the treatment of bile acid diarrhoea is simple and effective. Bile acid diarrhoea , however, is often not diagnosed because of a lack of easily available and reliable diagnostic methods. In the United Kingdom, the radiolabelled 23-seleno-25-homotaurocholic acid test is the gold-standard method of diagnosis. 23-seleno-25-homotaurocholic acid test, however, is expensive, inconvenient to the patient, involves radiation exposure and has limited availability. As such, a laboratory biomarker is desirable. This review briefly discusses the pathophysiology and management of bile acid diarrhoea and critically evaluates methods for its diagnosis, including serum 7α-hydroxy-4-cholesten-3-one, faecal bile acid measurement, serum fibroblast growth factor 19, urine-2-propanol, and the ¹⁴C-glycocholate breath and stool test.

Reverse T3 (3,3′,5′-triiodothyronine or rT3) is the third most abundant iodothyronine circulating in human blood and is produced by the inner ring deiodination of the pro-hormone thyroxine (T4). Unlike the more abundant and active metabolite T3, the measurement of serum rT3 is yet to find a routine clinical application. As rT3 binds weakly to the T3 thyroid nuclear hormone receptors, it is thought to represent an inactive end-product of thyroid hormone metabolism, diverting T4 away from T3 production. The analysis of serum rT3 has, up until recently, been measured by competitive radioimmunoassay, but these methods have been superseded by mass-spectrometric methods which are less susceptible to interference from other more abundant iodothyronines. Serum rT3 concentration is increased as part of the non-thyroidal illness syndrome, and by administration of common medications such as amiodarone which inhibit the metabolism of rT3. Serum rT3 concentration is also affected by genetic conditions that affect the iodothyronine deiodinases, as well as thyroid transporters and transport proteins. Analysis of rT3 can provide a useful diagnostic fingerprint for these conditions. rT3 has been shown to bind extra-nuclear iodothyronine receptors with a potential role in cell proliferation; however, the clinical relevance of these findings awaits further study.

Wernicke’s encephalopathy is caused by thiamine deficiency and has a range of presenting features, including gait disturbance, altered cognitive state, nystagmus and other eye movement disorders. In the past, Wernicke’s encephalopathy was described almost exclusively in the alcohol-dependent population. However, in current times, Wernicke’s encephalopathy is also well recognized in many other patient groups, including patients following bariatric surgery, gastrointestinal surgery, cancer and pancreatitis. Early recognition of Wernicke’s encephalopathy is vital, as prompt treatment can restore cognitive or ocular function and can prevent permanent disability. Unfortunately, Wernicke’s encephalopathy is often undiagnosed – presumably because it is relatively uncommon and has a variable clinical presentation. Clinical biochemists have a unique role in advising clinicians about potential nutritional or metabolic causes of unexplained neurological symptoms and to prompt consideration of thiamine deficiency as a potential cause in high-risk patient groups. The aim of this review is to summarize the clinical features, diagnosis and treatment of Wernicke’s encephalopathy and to highlight some non-traditional causes, such as after bariatric surgery.