This briefing describes the regulated use of the technology for the indication specified, in the setting described and with any other specific equipment referred to. It is the responsibility of healthcare professionals to check the regulatory status of any intended use of the technology in other indications and settings.
The NGAL Test reagent kit, calibrator kit and control kit, manufactured by BioPorto, got its CE marking on 31 January 2011. It is classed as an in vitro diagnostic device.
The NGAL Test is a laboratory test used to determine the level of a chemical known as neutrophil gelatinase-associated lipocalin (NGAL) in human urine and blood. Increased concentrations of NGAL may be caused by acute kidney injury. The NGAL Test could potentially therefore be used in the NHS to diagnose acute kidney injury.
The NGAL Test is promoted to be used in:
intensive care for monitoring
the emergency room as a triage tool
cardiopulmonary bypass surgery for monitoring
renal transplantation for predictive evaluation
nephrotoxicity assessment using intravenous contrast agents.
It is intended to be used with an automated clinical chemistry analyser by qualified laboratory staff (BioPorto 2013).
The NGAL Test is designed as a standard clinical laboratory test and can be used with most clinical chemistry analysers. The amount of NGAL present in samples of a patient's blood or urine is measured using a particle-enhanced turbidimetry laboratory technique. This involves quantifying the particles present in solution by measuring the reduction in transmitted light intensity through the sample. The assay takes about 10 minutes.
NGAL is a protein normally present in low levels in several human tissues. Its expression is greatly increased as a human immune response to inflammation and injury to epithelia (Cowland and Borregaard 1997).
In a person who is healthy, NGAL is filtered out of blood plasma by the glomeruli when it passes through the kidneys. NGAL is then reabsorbed back into blood plasma in the tubules. However, kidney inflammation in acute kidney injury can cause expression of NGAL directly into the urine (Tsigou et al. 2013) because there is a reduction in the glomeruli filtration rate and an increase in NGAL expression from the liver and lungs. This means that an accumulation of NGAL in blood plasma, with increased concentrations in plasma and urine, could indicate acute kidney injury.
Increased concentrations of NGAL can present earlier than other biomarkers used to detect acute kidney injury. Other conditions such as infection, hypertension, inflammation, anaemia and hypoxia can also cause increased concentrations of NGAL in urine and plasma (Tsigou et al. 2013), although not at the levels associated with acute kidney injury. Guidelines defining acute kidney injury use measurements of serum creatinine, urine output and, for children and young people, estimated glomerular filtration rate (eGFR), but do not include a definition of acute kidney injury based on measurement of NGAL.
Serum creatinine measurement is the recommended method for detecting and measuring acute kidney injury (NICE 2013). Measurement of urine output and eGFR can also be used. For each of these measurement methods, there are established ranges that define acute kidney injury: the recognised criteria of risk, injury, failure, loss of kidney function, and end-stage renal failure (RIFLE) (Bellomo et al. 2004); Acute Kidney Injury Network (AKIN 2007); and Kidney Disease Improving Global Outcomes (KDIGO 2012). However, there are limitations to standard methods. Serum creatinine values vary with age, sex, diet, muscle mass, drug intake and exercise and are affected by a compromised glomerular filtration. It can take up to 24 hours for changes in creatinine concentrations to become detectable. Urine output is an inconsistent measure because it is affected by non-renal factors such as bleeding, and there can be practical difficulties in measuring it accurately. eGFR is not considered appropriate in certain groups, including people with severe malnutrition, obesity or other extreme body size; exceptional dietary intake, such as a vegetarian diet or creatinine supplements; a skeletal muscle disease; paraplegia; high muscle mass; or an amputation (KCAT 2013).
The NGAL Test is one of a group of newer biomarkers that have been proposed for detecting acute kidney injury. The others include cystatin C, kidney injury molecule-1, interleukine-18 and fatty-acid binding proteins. None of the newer biomarkers are in clinical use in the NHS.
NICE is aware of the following CE marked diagnostic tests that appear to fulfil a similar function to The NGAL Test:
the NGAL Rapid ELISA Kit 037CE (BioPorto)
the ARCHITECT Urine NGAL assay (Abbott Diagnostics)
the Alere Triage NGAL Test (Alere Ltd).
Information on the cost of using the technology and alternative treatment options was sourced from the manufacturer and the literature (Shaw et al. 2011). Shaw et al. used a cost of £16 (inflated to 2012 prices) for the combined tests of serum creatinine, blood urea nitrogen and urine output. A cost of £27 (inflated to 2012 prices) was used for a urinary NGAL test. However, blood urea nitrogen is not used routinely in the UK and Shaw et al. did not provide the source of the costs, so these estimates should be treated with caution. The cost of testing for serum creatinine (by the Jaffe method) alone is around £2 per test.
The average cost per test of The NGAL Test is estimated to be £24, assuming the test reagent kit, controls and standards can be used for about 100 patients. The individual components needed for the test are The NGAL Test Reagent kit (£1770), the calibrator kit (£213) and the control kit (£417). The lifespan of the technology is thought to be 24 months from manufacturing, with open vial stability and on board stability of 30 days. At 2–8°C, the calibrator and control kits have a shelf life of 24 months from manufacture and an open vial stability of 4 weeks. There are no costs available for service, maintenance or training with The NGAL Test or alternative options. It is estimated that The NGAL Test or alternative options will be used about 4 times in cardiac surgery patients (Shaw et al. 2011) and might be used more often in other clinical settings like monitoring intensive care unit patients.
A nephrologist is needed to interpret NGAL, serum creatinine, blood urea nitrogen and urine output measurements, but the staff time is not expected to be more than for current tests.
The technology is intended to be used in the detection phase of the identification stage of the NICE pathway on acute kidney injury.
The NGAL Test is not used in clinical practice in any hospitals in the UK, but it is being used in research projects in some institutions.
Measurement of serum creatinine was stated as the primary method of detecting acute kidney injury. A lack of clinical evidence was the main reason given by some clinicians for not currently using The NGAL Test in clinical practice. Some clinicians reported using the test for research purposes, but none reported using it in clinical practice in the UK.