Point-of-care creatinine devices to assess kidney function before CT imaging with intravenous contrast

Historically contrast agents were much more toxic than those used in current practice, with side effects including kidney damage. Clinical experts noted that the risk of developing acute kidney injury (AKI) from contrast agents currently used in the NHS is thought to be very low, especially in people with an estimated glomerular filtration rate (eGFR) of 30 ml/min/1.73 m² and above. However, they noted that there is some concern about the risk of post-contrast AKI (PC‑AKI) for people with an eGFR of less than 30 ml/min/1.73 m², especially if they have other risk factors for kidney disease. Although end-stage renal disease after PC‑AKI is extremely rare, transient rises in creatinine (decreases in eGFR) can have clinical effects and increase mortality, especially if there are repeated rises. Patient experts noted that when a contrast-enhanced CT scan does lead to substantial kidney damage, the effect on a person's quality of life can be considerable. The committee concluded that the risk of PC‑AKI is very low for most people, but there may be a higher risk if eGFR is less than 30 ml/min/1.73 m².

NICE's guideline on acute kidney injury recommends that the risk of AKI should be assessed before offering iodinated contrast agents to adults for emergency or non-emergency imaging, and that increased risk is associated with an eGFR less than 40 ml/min/1.73 m². However, the Royal Australian and New Zealand College of Radiologists iodinated contrast guidelines, which have been endorsed by the Royal College of Radiologists, recommend that an eGFR is only needed before offering iodinated contrast agents if there are risk factors for AKI. The committee noted that these 2 approaches have resulted in variation in clinical practice in the NHS. Some trusts need a recent eGFR result from all patients before doing a contrast-enhanced CT scan. Other trusts will do a contrast-enhanced CT scan without a recent eGFR result if there is a low risk of AKI. The definition of 'recent' may vary between 3 and 12 months in practice.

The evidence showed that the 3 devices with diagnostic accuracy data (ABL800 FLEX, i‑STAT Alinity and StatSensor) perform reasonably well in classifying eGFR into the correct categories. The committee noted that measuring creatinine using the point-of-care (POC) creatinine devices is not as accurate as laboratory measurement. Therefore, there would be some false positive results (incorrectly categorised as eGFR below 30 ml/min/1.73 m²; people would have intravenous hydration unnecessarily) and false negative results (incorrectly categorised as an eGFR of 30 ml/min/1.73 m² and above; people would miss out on intravenous hydration). However, the number of these would be small. A clinical expert explained that the tests are more accurate at high levels of creatinine (low eGFR values), which is when clinical decision making is the most critical. StatSensor appeared to be less accurate than the other 2 devices, but the committee noted that the 95% credible intervals for sensitivity for the different devices overlapped. This means that the sensitivity of StatSensor could be as good as the other devices. The committee acknowledged that the laboratory reference standard used to calculate diagnostic accuracy for the POC creatinine devices was assumed to be 100% accurate, which is probably not the case. It also noted that the studies would have been done under controlled conditions and that the devices may not perform as well in clinical practice. The committee concluded that there was some uncertainty about whether ABL800 FLEX, i‑STAT Alinity and StatSensor can correctly categorise eGFR, but in general, the accuracy of the devices was acceptable.

The diagnostic accuracy studies included very few people with an eGFR less than 30 ml/min/1.73 m². The committee noted that although this could affect the confidence placed on sensitivity calculations, it does reflect clinical practice because most people present for an outpatient CT scan with an eGFR of 30 ml/min/1.73 m² and above. The committee concluded that further research in a population with eGFR less than 30 ml/min/1.73 m² would be beneficial (see section 5.1).

The value of the POC creatinine devices is that they prevent the cancellation and rebooking of CT scans, reduce PC‑AKI and improve the experience for patients attending for a CT scan by allowing same day assessment and decisions. The committee noted that there was no evidence on these outcomes and encouraged further research incorporating them (see section 5.3).

The model only included people who present for an outpatient CT scan without a recent (within 3 months) eGFR result; it did not assess strategies for increasing the number of people who present for their CT scan with a recent eGFR result. The committee considered that the structure, inputs and assumptions used in the model were appropriate. It noted that the external assessment group (EAG) was unable to include the effect of delaying a planned CT scan on clinical outcomes relating to the underlying condition during a wait for a rescheduled scan. This was because there are many different reasons for having a CT scan and the effect of them all could not be quantified. The committee also noted that costs for training and laboratory governance of the POC creatinine devices were not included. A clinical expert explained that laboratory governance costs can vary considerably between trusts, depending on how much POC testing is already done across the trust and whether IT connectivity is already in place. The EAG estimated that annual implementation and governance costs would have to be over £80,000 to change conclusions from the economic model. Clinical experts agreed that these costs would be much lower than this and therefore concluded that the model analyses were acceptable for decision making.

The testing strategy in which people presenting for a CT scan without a recent eGFR had no further testing and had a contrast-enhanced scan without intravenous hydration resulted in the highest net benefit. The committee considered however, that no testing for anybody, regardless of whether risk factors were present, and giving contrast agent to all without intravenous hydration was not an appropriate comparator in the model. This was because it is not in line with national and international guidelines, which recommend assessing the risk of AKI because, although rare, when PC‑AKI does occur the consequences for an individual are substantial (see section 4.1).

The differences in quality-adjusted life years (QALYs) between the different testing strategies assessed were extremely small. The strategy in which all people presenting for a CT scan without a recent eGFR would have a laboratory test was associated with more QALYs than the strategies involving a POC creatinine device. The EAG explained that this was because the number of false negative test results (that is, when true eGFR is less than 30 ml/min/1.73 m² but the test suggests an eGFR of 30 ml/min/1.73 m² and above) is higher for strategies including POC creatinine devices than for the laboratory test (which is assumed to have 100% sensitivity). However, the QALY gain from appropriately managing treatment for people who have an eGFR of less than 30 ml/min/1.73 m² is very small. The committee concluded that overall the clinical effectiveness is very similar across the different strategies. But it noted that the effect on quality of life for the small number of people who do develop kidney damage after a contrast-enhanced scan can be considerable (see section 4.1).

In the model, the POC creatinine devices were assumed to be used only for measuring creatinine and calculating eGFR, but the committee noted that some of the devices have multiple uses. For example, the ABL800 FLEX can measure 18 analytes, but test costs were not apportioned to other uses. Therefore, the cost per test for ABL800 FLEX was higher than for the i‑STAT Alinity and StatSensor. This led to strategies including ABL800 FLEX having lower net benefit than strategies involving i‑STAT Alinity or StatSensor. The committee noted that, depending on the setting of the radiology department, an ABL800 FLEX could also be used by different departments, which would reduce the cost per test because the throughput would be higher.

In the model, if a scan was cancelled and rebooked because of a positive POC creatinine test result or the need for a laboratory test, then a cost of £87.92 (equal to the cost of an unenhanced scan) was included. The committee noted that this assumes that the cancelled CT scan appointment cannot be filled. Clinical experts explained that in radiology departments that do both acute (emergency and inpatients) and elective (outpatient) CT scans these cancelled appointments would be filled by other patients waiting for CT scans. However, if the radiology department only does elective CT scans, for example a mobile clinic, then the cancelled appointment is unlikely to be filled and the cost assigned to a cancelled scan is appropriate. The committee also considered that using an unenhanced CT reference cost as a proxy for the rebooked CT scan could overestimate the opportunity cost because the cost of cancellation would already be accounted for in the fully absorbed reference cost. The committee noted that a scenario analysis of the model was run in which no CT scans were cancelled because of a laboratory test. The results of this analysis showed that the strategies of laboratory testing for all or risk factor screening followed by laboratory testing were the most cost effective. However, in the scenario in which 25% of CT scans were cancelled because of a laboratory test, laboratory testing for all returned to being the least cost-effective strategy. The committee acknowledged that cancelled CT scans are not only an opportunity cost for the NHS, but would not be good for patients, who would have to return to the hospital for a rebooked CT scan. The committee concluded that there was uncertainty in the opportunity cost associated with cancelling CT scans and therefore in the optimal strategy.

Strategies in which risk factor screening was done first followed by a POC creatinine test for people who were identified as having at least one risk factor were more cost effective than strategies in which POC creatinine testing was done for all people presenting for a CT scan without an eGFR. The committee noted that including risk factor screening as a first step reduced the number of POC creatinine tests that would be done, which reduced the overall cost of testing. In the model, risk factor screening was assumed to be done with a generic risk factor questionnaire that had 100% sensitivity and 65.2% specificity. The committee agreed that risk factor screening should identify people at higher risk of AKI. But it noted that defined questionnaires had not been assessed, although risk factors are clearly stated in national and international guidelines. The committee concluded that risk factor screening is likely to be an appropriate first step for people presenting for a CT scan without an eGFR, but that further research should be done to develop a suitable risk tool or validate an existing risk tool for use in the NHS (see section 5.2).

The strategies with the highest net benefit in the model were those that combined risk factor screening, a POC creatinine test for all people identified as having at least one risk factor, and a final confirmatory laboratory test for people who have a positive test result from a POC device. A confirmatory laboratory test would result in the CT scan being cancelled and rebooked. In practice this often means that the referral for CT would be cancelled, resulting in another referral having to be made for the patient. A patient expert explained that cancelling a CT scan would not be good for patients and their carers because it would take time to go for a blood test, wait for another referral and return to the hospital for the rebooked CT scan. This may also be associated with travel expenses, time off work, and anxiety about the scan and the underlying clinical condition, most of which were not captured in the model. The committee noted that people with a true eGFR of 30 ml/min/1.73 m² and above who are identified as having an eGFR of less than 30 ml/min/1.73 m² using a POC creatinine device (false positive) would have intravenous hydration unnecessarily, which is associated with additional cost, but not with a QALY loss. It therefore concluded that although a strategy with a confirmatory laboratory test is slightly cheaper, it should not be considered further because of the negative experience for patients and their carers of cancelling the CT scan, going for a blood test and returning for the rescheduled CT scan.

Men, people over the age of 60, and those of African-Caribbean, African or South Asian family origin are at higher risk of kidney disease than others. The committee noted that people of these family origins are not often included in research studies, but the availability of POC creatinine devices could have a greater benefit for them than for the rest of the population. This is because in some trusts if a person is at low risk of PC‑AKI, eGFR would not be measured before a contrast-enhanced CT scan (see section 4.2). Men, people over the age of 60, and those of African-Caribbean, African or South Asian family origin thought to be at low risk of PC‑AKI based on clinical factors may still have a higher risk than other people.

The committee concluded that using POC creatinine devices to guide the use of contrast in outpatient CT scans is likely to be cost effective and improve patient experience if current protocols need all outpatients to have a recent eGFR result before a contrast-enhanced CT scan can be done (see section 4.2). The committee agreed that the most appropriate testing strategy was to use a risk factor screening questionnaire and then a POC creatinine device to test people with one or more risk factors (see section 4.11), without laboratory confirmation of positive test results (eGFR less than 30 ml/min/1.73 m²; see section 4.12). It acknowledged that:

• POC creatinine test results should not be used to make decisions about care other than the decision to give contrast agent because of their lower accuracy than laboratory creatinine measurement.

• POC creatinine testing should be set up and run as a collaboration between the radiology department and the pathology laboratory.

• POC creatinine testing should only be done when clear laboratory governance structures for point-of-care testing are in place.

The committee noted that a risk of PC‑AKI should not prevent diagnostic images being taken to inform treatment decisions. All patients in whom contrast-enhanced CT imaging is indicated should get a form of imaging that enables access to treatment they might need. The committee acknowledged that POC creatinine devices are less accurate than laboratory creatinine testing. Therefore, patients who arrive at a CT scan appointment with a recent eGFR result are most likely to have appropriate management of their condition. The committee noted that these patients were not included in the economic model, but that a scenario in which all referrers provide an eGFR measurement before a CT scan appointment is likely to be the optimal approach, and that this approach should be encouraged to avoid higher numbers of patients needing POC creatinine measurement before a contrast-enhanced CT scan.