The technology

The NephroCheck test (Ortho Clinical Diagnostics) measures urinary levels of tissue inhibitor of metalloproteinase 2 (TIMP-2) and insulin-like growth factor binding protein 7 (IGFBP7). The test is intended to be used in the early detection of acute kidney injury (AKI) because these markers are thought to be involved in the development of renal tubule injury. The company claims that TIMP-2 and IGFBP7 have an additive predictive value if used together.

The test procedure involves adding fresh urine samples to a buffer mixed with a fluorescent antibody conjugate. The sample is then applied to a cartridge and inserted into the platform for incubation, reading, result calculation and result display. The plastic cartridge is single use and contains sandwiched immunoassays for TIMP-2 and IGFBP7. It has a shelf life of 52 weeks and must be used on 1 of 2 specified platforms, either:

  • NephroCheck test cartridge on a benchtop instrument (Astute140Meter) or

  • VITROS NephroCheck test cartridge on a laboratory instrument (VITROS 3600 Immunodiagnostic System or VITROS 5600 Integrated System).

The procedure takes about 20 minutes and the output is a single number called the AKI risk score. The test score is derived from multiplying the concentrations of the 2 biomarker levels. An AKI risk score of 0.3 or less indicates a low risk of developing moderate to severe (AKI stage 2 and AKI stage 3) AKI within 12 hours of the assessment, while an AKI risk score of greater than 0.3 suggests a high risk of developing moderate to severe AKI within 12 hours.

Innovations

The company claims that the biomarkers measured by the NephroCheck test predict kidney injury earlier than current clinical assessment and tests. This enables appropriate intervention that may prevent progression to a more severe injury. The test differs from current markers of renal injury in that the 2 markers are claimed to be less likely to be elevated by common comorbidities such as diabetes, chronic kidney disease and sepsis.

Current care pathway

The definition of AKI covers a wide spectrum of injury and is typically characterised by increased serum creatinine (SCr) levels and decreased urine output. Attempts at defining and staging AKI as a set of functional criteria have led to the following classifications:

  • RIFLE (risk, injury, failure, loss of kidney function, end-stage kidney disease)

  • AKIN (Acute Kidney Injury Network)

  • KDIGO (Kidney Disease: Improving Global Outcomes).

Early diagnosis of AKI remains a challenge; the NICE guideline on acute kidney injury: prevention, detection and management, which is being updated, puts emphasis on early intervention and stresses the importance of risk assessment and prevention. The guideline recommends using a multi-parameter approach including clinical indicators of functional decline such as raised SCr levels, estimated glomerular filtration rate (eGFR), reduced urine output and other factors such as age, use of nephrotoxic drugs and comorbidities to identify at-risk patients. Patients considered to be at risk are offered preventive therapy.

Increased SCr levels and reduced urine output are consequences of an earlier injury to the kidney and may not manifest for up to 48 hours after the injury has occurred.

It is suggested that TIMP-2 and IGFBP7 levels rise rapidly early in the process of injury to kidney cells, allowing earlier intervention when increased levels are found.

NICE has published a medtech innovation briefing on the NGAL test for early diagnosis of AKI.

Population, setting and intended user

The NephroCheck test system is intended to be used in addition to clinical evaluation and standard diagnostic tests, such as serum creatinine, as an aid to assess the risk of moderate or severe AKI. It is most likely to be used in critically ill patients, including those who have had major surgery. The test is intended to be done in a laboratory by a trained technician, or in a near-patient setting by a trained healthcare professional.

Costs

Technology costs

The VITROS 3600 Immunodiagnostic and VITROS 5600 integrated laboratory systems can be used for a variety of tests; it is not anticipated that a hospital will purchase either of these platforms solely to use NephroCheck. If neither of the laboratory systems, or an Astute140 meter is available, a hospital adopting the test is likely to purchase the benchtop Astute140, which costs £3,000 excluding VAT. Each single use NephroCheck cartridge costs £49.80 excluding VAT.

Resource consequences

NephroCheck would be an additional cost compared to standard diagnostic testing for AKI. These costs may be offset if early detection resulted in appropriate nephro-protective care and avoided resource-intensive treatments such as renal replacement therapy. Further cost savings may arise from avoiding unnecessary preventive care in patients not at risk, and so avoiding the cost of managing any adverse events arising from this. There is no published economic evidence to support this. Training for laboratory staff is provided by the company.

Currently, 3 NHS organisations have used the NephroCheck test.