Identifying on admission patients likely to develop acute kidney injury in hospital

Acute Kidney Injury (AKI) is emerging as an important clinical syndrome which is associated with poor clinical outcomes. AKI, previously known as Acute Renal Failure, refers to a sudden reduction in kidney function.

The majority of AKI is caused by sepsis and hypovolaemia. Other causes include renal tract obstruction and intrinsic renal disease. Around 1 in 5 adult hospital admissions are associated with AKI [3]. AKI is present on admission in around 60% of all patients with AKI detected in hospital [4]. AKI is associated with high mortality rates; from 8 to 18%, 22–33%, and 32–36% mortality for patients with AKI Stages 1, 2, and 3 respectively, whilst in the absence of AKI, mortality runs at 2% [4–6]. Consequently, in England AKI may be associated with as many as 40,000 excess deaths each year [6]. Hospital inpatient AKI care has been estimated to cost £1 billion each year, and effective prevention of AKI could save up to £200 million per annum [6].

The 2009 National Confidential Enquiry into Patient Outcome and Death (NCEPOD) AKI report found that care could have been improved for 50% of patients [7]. Since the NCEPOD report, great strides have been made in hospital AKI care, including the introduction in UK hospitals of an AKI algorithm to detect AKI and national advice on what an AKI Bundle should include [2, 8]. Clinically recognised risk factors for AKI include modifiable factors (e.g. use of iodinated contrast, use of certain medications) and non-modifiable factors (e.g. age, the presence of chronic kidney disease) [9]; combinations of these modifiable and non-modifiable factors appear to multiply risks of developing AKI. Roberts et al. describe that age alone is closely associated with the number of AKI risk factors patients have, as well as itself being associated with AKI [10].

Given that approximately a third of patients with AKI in hospital develop AKI during their stay in hospital, two-thirds of patients with AKI in hospital have AKI at the time of admission [4]. So, there is an opportunity to prevent the development of AKI in a large number of patients: in cases of AKI developed whilst in hospital, 20% are avoidable [7]. An AKI risk prediction tool could identify patients at high risk of AKI and provide the attending medical teams the opportunity to prevent the development of AKI by intervening in patients’ current care. For example, staff would be alerted to the risk faced by individual patients, prompting a review of the patient’s current clinical condition, and current medication, which may lead to increased clinical monitoring or a change in treatment. This could cut rates of AKI, leading to a reduction in morbidity, mortality, and length of stay.

We describe an attempt at predicting which patients will go on to develop AKI in hospital, and specifically which Stage of AKI. This is undertaken using methods based around fuzzy logic which are then calibrated against more conventional approaches.

Three fuzzy logic systems (FLS) (FLS I, II, III) and three multivariable logistic regression (MLR) models (MLR I, II, III) were constructed to stratify patient risk for developing AKI (any Stage), either Stage 2 or 3 AKI, or Stage 3 AKI respectively during a stay in hospital. Each model was parameterised with data from a time period and validated using data from a later period. Data was provided by RCHT. Each FLS was distinguishable from the other due to the different sets of risk factors used in defining FLS I, II and III respectively.

AKI is categorised into three Stages according to severity. The KDIGO stages of AKI are identified using creatinine measurements from blood tests, or from the reduction in urine output. Other methods to identify AKI such as using novel biomarkers are not used in practice, are evolving, and so were not analysed as part of this study [21]. Current practice only assesses the likelihood of developing AKI (in stages 1, 2, or 3) and does not offer discriminated risk assessment, especially for more dangerous stages of AKI later during their hospital spell, including Stage 2 AKI (22–33% mortality) and Stage 3 AKI (32–36% mortality). This discriminated capability is provided by our risk assessment model through the use of a fresh set of risk factors for each stage of AKI.

Each patient carries a risk of developing AKI at any time during hospitalisation. Research presented here quantifies that risk using information obtained at the point of admission and within the patient’s first two days in hospital. Additionally, the capability to assess the risk of acquiring the more severe strands of acute kidney injury has never previously been attempted using a TSK FLS.

According to this research, use of FLS III could quickly have identified, within the first two days of a hospital spell, all 14 patients who went on to develop Stage 3 AKI during their stay. Moreover, with a specificity of 83%, use of the same model would have falsely identified as “high risk” 17% of patients carrying low risk.

Susceptibility to either Stage 2 or Stage 3 is assessed by FLS II which correctly classifies 61% of high-risk patients and 73% of patients at low risk. Model performance for forecasting the development of any Stage of AKI, using FLS I, was marginally worse, predicting 62% of cases that develop in RCHT and 64% of people not developing the disease.

The purpose behind development of FLS I was to forge comparison with risk tools previously assembled and, thereby assess the suitability of the selected input parameter set in predicting the patients at risk of developing AKI. Therefore, using the same model development technique but with either a refined or an expanded input parameter set, including prospectively collected data, enhanced predictive accuracy might be achieved.

FLS II and FLS III model in particular cannot be properly assessed against prior studies as this is the first attempt at quantifying the risk of developing specific Stages of AKI for a broad cohort of both medical and surgical inpatients. So, we believe our study has generated unrivalled accuracy in identifying patients at risk of Stage 3 AKI (AUC = 0·95, 95% CI: 0·92–0·92). For Stage 2 or 3 AKI, FLS II model performance dropped comparatively (AUC = 0·77, 95% CI: 0·69–0·85), to a level lower than the AUC = 0.9 (95% CI: 0.9–0.9) and AUC = 0.87 (95% CI: 0.87–0.87) resulting from the application of a Gradient Boosting Machine algorithm forecasting patients developing Stage 2 AKI within 24 and 48 h respectively [22]. However, the approach presented here identifies patients at elevated risk of AKI up to a week ahead, allowing for a longer period of mitigating measures to be implemented. Likewise, a week is longer than the forecasting window employed in other research which used ward-monitored serum creatinine to predict onset of each Stage of AKI over the following 24 h [23]. Despite this shorter window, the AUC of 0.83 (95% CI: 0.83–0.84) for Stage 3 AKI underperformed FLS III.

Another attempt at stratifying the risk of AKI development in-hospital used electronic patient data gathered 24 h either side of admission. Although categories employed to portray disease severity do not match AKI Stages used in this research and in clinical practice, an AUC of 0.75 (95% CI: 0.73–0.76) resulted [24]. In the case of FLS I the accuracy of our approach fell slightly further (AUC = 0·70, 95% CI: 0·64–0·77). However, the AUC for FLS I is comparable with a validation of an AKI Prediction score which was applied to identify development of hospital-acquired AKI in general medical and surgical admissions; for medical patients with no known baseline serum creatinine an AUC of up to 0.71 was achieved [25]. This contrasts to a number of studies which have looked to assess the risk of AKI in medical admissions. In analysing 898 patient records Roberts et al. generated AUC values of approximately 0·7 [10]. Marginally better levels of model performance were obtained by a study in Sussex, UK (AUC = 0·72) [26]. Similarly, a study from a hospital in Kent, UK processed data from non-maternity, emergency admissions only and predicted the onset of AKI on admission (AUC = 0.75) and 72 h post admission (AUC = 0·68) [27].

In addition to forecasting AKI up to a week prior to development, our study utilises data obtained 24 h either side of admission, thereby reducing computational burden. This contrasts to an approach which uses data gathered across varying windows, up to 30 days prior to admission [28]. Although the AUC reached 0.765, 0.73 and 0.7 (to predict AKI at times 1, 2 and 3 days prior respectively), patients in this cohort were limited to between 18 and 64 years old, and the researchers did not explore the applicability of the models for the elderly.

Our study performs less well than that employing up to five modelling techniques using data collected within the first 24 h of a hospital stay from patients aged 60 or over (AUC = 0.74, 95% CI: 0.73–0.76) [29]. However, in addition to the age restriction, the research used variables which were not available electronically for all patient admissions at RCHT, e.g. BMI and Family History.

FLS I, however, has comparable performance to all of these studies, and uses data from both medical and surgical patients and both emergency and non-emergency.

According to our study data, mortality from AKI across our study period stood at 38% for Stage 3 and 17% for both AKI Stage 1 and AKI Stage 2. Given approximately 30% of cases are considered preventable, we propose that use of an accurate risk assessment tool for the development of in-hospital AKI Stage 3 could save lives. Based on the results presented in this study, the use of FLS III could evolve the potential to avoid some of these deaths.

The ability of FLS III to predict patients at low risk of AKI Stage 3 is not as good as it is for those at high risk. Falsely mitigating against some conditions, e.g. Deep Vein Thrombosis, can bring about unacceptable risks, i.e. bleeds. However, we consider the potential harm to the patient from inappropriate mitigation is likely to be sufficiently outweighed by the marginal risk caused by withholding measures. So, the use of a tool such as FLS III is worthy of health economic testing for the prevention of AKI Stage 3 in hospital.

These measures might be considered low-cost and add minimal risk for patients to whom they are unnecessarily introduced, including those falsely identified as being at high risk. The specificity results of this study indicate that mitigating measures will be unnecessarily introduced to roughly a third of patients carrying low risk who are expected to stay more than two days in hospital. In addition, given the lack of intrusiveness as these measures are introduced to patients, this is likely to be considered acceptable.

The performance of each FLS was assessed against MLR, a methodology more traditionally employed in developing risk assessment frameworks in healthcare. In all three models, the performance of FLS was at least as good as MLR, perhaps signalling that FLS could be employed more widely in health risk assessment and epidemiological research.

It is hypothesised that by identifying a patient’s risk of developing AKI Stage 3 at the earliest point possible during a patient spell this will increase survival. Based on the data period within this study, the fraction of patients dying in hospital following a diagnosis of Stage 3 AKI during hospitalisation stands at 38% (25 out of 66). Assuming one fifth of these cases were preventable and FLS III would have early identified 80%, use of this risk assessment tool could have prevented approximately 4 deaths during the same hospital stay.

Of 304 patients who went on to develop Stage 1 or Stage 2 AKI, 53 died. Assuming one fifth preventable and a FLS sensitivity of 60%, a further 6 lives might have been saved with early risk assessment.

However, these claims should be tempered because later development of AKI can be a signature of a general end-of-life decline and greater mortality risk [24]. Nevertheless, due to the high levels of predictive accuracy achieved by research and given that 20% of cases of AKI developed in hospital are avoidable, it offers considerable potential to cut the in-hospital burden of the disease if accompanied by appropriate mitigating measures.

Acute Kidney Injury can develop in patients in hospital with the severest type, Stage 3, having a mortality rate of between 30 and 40%. With appropriate mitigation, some cases can be avoided. We have used anonymised data taken from patients as they were admitted to hospital to create risk assessment models using Fuzzy Logic and multivariable logistic regression. The models were trained to recognise patterns in data and distinguish between those patients who went onto develop AKI any Stage, AKI Stage 2 and 3, or AKI Stage 3 and those who did not develop AKI at all. This was the first attempt at building separate models for the three currently recognised degrees of AKI severity and upon testing the models, our ability to predict AKI Stage 3 was very strong, albeit on a small number of cases. Subsequently, our view is given that AKI is preventable in some cases and any technology containing these models is designed to be deployed early on in a patient’s stay, it has the potential to save lives.