Nephrology In-Reach Services Lead to Improvement in Mortality in Acute Kidney Injury – 3 (AKI-3)

Background: Acute Kidney Injury (AKI) is a sudden decline in kidney function. Early detection and prompt treatment of AKI is vital in improving the outcome of patients. We introduced in-reach nephrology services at South Tyneside District Hospital (STDH) as part of a reconguration of local NHS services. Aims: The principal aim of this study is to analyse patient outcomes relating to service developments and to explore prognostic characteristics among a cohort of AKI-3 patients Design: This was a single centre retrospective impact evaluation study. Methods: We studied all patients (n=246) who either presented with or developed AKI-3 during their admission at South Tyneside District Hospital from 2016 to 2018. The inclusion criteria included age 18-95 years and a diagnosis of AKI-3 as per KDIGO classication. Exclusion include those on established dialysis regime or on palliative care. Results: A total of 246 patients were admitted with AKI-3. There were 64 deaths from AKI-3 over the three-year period. Mortality decreased from 29.5% to 20.7% from 2016 to 2018. In patients with Community Acquired (CA-AKI3) the overall mortality rate was 24.2% (n=182), whereas the overall mortality rate of those with Hospital Acquired (HA-AKI3) was 31.3% (n=64). The pre-AKI use of ACEi, A2RB or diuretics increased from 39.7% in 2016 (n=78), to 59.3% in 2017 (n=86) and 64.6% in 2018 (n=82). Conversely, mortality associated with the use of these medications reduced each consecutive year (32.3%, 25.5%, 18.9%). Conclusion: Development of nephrology in-reach services, staff education measures and a primary care pathway could reduce AKI-3 mortality among patients in inpatient and community settings.


Background
Acute Kidney Injury (AKI) is a clinical syndrome de ned as a sudden decline in kidney function, characterised by a rise in serum creatinine levels, with or without a reduction in urine output. It has evolved as a major health issue affecting numerous patients globally, eventually leading to reduced life expectancy [1]. Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline has recently rede ned the criteria for recognising AKI, and implemented a new three-stage classi cation of severity [2].
The increase of morbidity and mortality among AKI patients has been well established, namely the development of end-stage renal disease and cardiovascular events [3]. According to a review by Coca et al., patients hospitalized with AKI had increased long-term adverse outcomes compared to their counterparts without AKI [4]. Another study by Chertow et al. depicted an increased mortality, length of inpatient stay and hospital cost as a direct result of developing AKI [5]. The incidence of AKI also increases hospital spending, with an estimated £1 billion annual cost of inpatient AKI-related care accounting for 1% of the annual NHS budget [6].
In addition to the wider adverse consequences of AKI on nance and mortality, the patients may present with various compounding factors such as existing co-morbidities and medications that potentially worsen individual outcomes [7]. In the United Kingdom, Think Kidneys has launched a nationwide kidney awareness campaign to equip healthcare professionals with the knowledge and resources required to recognise and prevent the development of AKI. Recent guidance from the National Institute for Health and Care Excellence (NICE) [8] and National Con dential Enquiry into Patient Outcome and Death [9] was issued to improve early recognition and management of AKI. Internationally, there have been quality improvement projects that explore and a rm the need for service improvement, particularly regarding early recognition, specialist outreach support and staff education [10,11,12].
In this study, we aim to analyse the evolution of patient outcomes relating to site-wide service developments over three years. We also aim to explore its effects on a range of variables known to affect clinical outcome among a cohort of AKI patients, such as co-morbidities and medications.

Study Population
We conducted a cohort study from 2016-2018, between the dates of 1 st September and 31 st December. This period was chosen as during this period the hospital services traditionally receive multi-morbid patients with complications. This period has been commonly called as the "winter pressure" period. The study took place at South Tyneside district hospital (STDH), belonging to the South Tyneside and Sunderland NHS Foundation Trust (STSFT). STDH serves the population of South Shields and neighbouring boroughs and is situated in the North-East of England. Its population is circa 150,000 (ONS data, 2016), with a larger proportion of people aged 50+ years compared to the rest of the country. We collected data from 1 st September to 31 st December 2016 to guide our interventions.
We studied all patients (n=246) who either presented with or developed AKI-3 during their admission at STDH within the mentioned timeframe. Data was retrieved using hospital electronic patient record systems. The inclusion criteria included age 18-95 years and a diagnosis of AKI-3 as per KDIGO classi cation at presentation or during hospital stay. Patients on an established dialysis regime or on palliative care were excluded from the study.
Re ecting the KDIGO diagnostic criteria, AKI was diagnosed as such: Increase in SCr by ≥0.3 mg/dl (≥26.5 mmol/l) within 48 hours; or Increase in SCr to≥1.5 times baseline, which is known or presumed to have occurred within the prior 7 days; or Urine volume <0.5 ml/kg/h for 6 hours.
AKI was staged into AKI 3 if any one of the following criteria was met: Increase in serum creatinine was ≥3.0 times baseline OR Increase in serum creatinine to ≥4.0 mg/dl (≥353.6 mmol/l) OR Initiation of renal replacement therapy (RRT) OR <0.3 ml/kg/h of urine for ≥24 hours OR Anuria for ≥12 hours Service improvement interventions to improve patient outcome This site did not have any in-reach of renal services prior to December 2016. Due to local NHS service reorganisation and merger of two trusts renal in-reach services were established. Between each year of study, we implemented changes with the aim to improve patient outcomes.
Educational awareness programme for primary and secondary care teams. This included regular teaching sessions for the clinical teams on the site. The teaching was delivered by a consultant nephrologist in focussed groups including Foundation year 1 trainee teaching, core medical trainees teaching and during weekly clinical meeting attended by all clinical staff members.
Nephrology in-reach and inpatient service from the local renal centre. This included establishment of two general nephrology clinics on site and two sessions every week for a consultant nephrologist to review patients presenting with AKI or those needing specialist renal input.
Creation of an AKI Online Health Pathway tool for primary care, in accordance to South Tyneside Clinical Commissioning Group (CCG) protocols.
The primary outcomes of this study were as follows: in-hospital mortality, length of hospital stay and the recovery of renal function. Secondary outcomes included incidence of common co-morbidities (diabetes mellitus, hypertension, left ventricular failure and liver disease); treatment with RRT; incidence of de ned medications (ACE-Inhibitors (ACEi), Angiotensin II Receptor Inhibitors (A2RB), Diuretics.

Statistical Analysis
The categorical variables are presented as percentages and rates, while continuous and skewed variables were expressed in terms of the mean value.
Statistical analysis was performed using the 26 th version of the SPSS software.
Results on analysed individual variables across the three years were presented as percentage values. The overall cohort analysis also includes relative risk of the examined variables against mortality. We used Pearson's Chi-Squared test to evaluate correlations between mortality and a range of different factors. We accepted categorical variables with p≤0.050 as having a statistically signi cant correlation. To compare overall mortality between 2016 to 2018, the use of ACEi, A2RB or Diuretics from 2016-2018 and to evaluate signi cance on any observed trends, we used Independent T-Test analysis.

Results
A total of 246 patients developing AKI-3 during the study period. 182 of these patients developed AKI-3 in the community and were admitted to hospital as compared to the 64 patients who developed their AKI-3 as an inpatient. However, a gradual rise in incidence of hospital acquired AKI (HA-AKI3) was noted as compared to community acquired AKI (CA-AKI3) during the study period (Table:1).
The mean age of incidence of AKI was similar over three years, with mean age being between 68 and 71. The average length of hospital stay was shortest in the rst year of study; 15.3 days in 2016, compared to 26.5 days in 2017, and 23.6 days in 2018. Of the 246 patients admitted, there were a total of 64 deaths.
Most of these deaths were in male patients, comprising of 38 out of the 64 (59.4%). There was an annual decline of overall mortality throughout the study period, from 29.5% (n=78) in 2016 to 20.7% (n=82) in 2018.
Over the three years, there was a decreasing trend in Renal Replacement Therapy (RRT) treatment; dropping from 9.0% of all patients admitted with AKI-3 in 2016, to 7.0% in 2017, and again to 4.9% in 2018. Out of the 17 patients who were treated with RRT, there was only one death recorded, resulting in a statistically signi cant correlation between the two variables (p=0.050).
Out of the patients with CA-AKI3 the overall mortality from 2016 to 2018 was 24.2% (n=182), whereas the overall mortality of those with HA-AKI3 was 31.3% (n=64). The relative risk of HA-AKI3 and mortality was 1.29, which indicates an increased risk of death among those with HA-AKI3 when compared to the CA-AKI3 cohort. The rate of change for creatinine levels among CA-AKI3 patients on admission compared to baseline increased from 2016 to 2017 and dropped marginally in 2018. Conversely, AKI-3 creatinine on discharge compared to baseline fell from 2016 to 2017 but increased slightly in 2018.
The study examined the prevalence of ACEi, A2RB or diuretics (the de ned medications) in patients who developed AKI-3. An upwards trend was observed when examining the annual use of A2RBs and diuretics, whereas no trend was observed in the use of ACEi. Despite the number of patients on diuretics pre-AKI increasing, associated mortality in this patient group dropped from 42.1% in 2016 (n=19) to 25.0% in 2018 (n=36). Similarly, the mortality of patients on A2RB decreased each year, from 42.9% (n=7) in 2016 to 18.8% (n=16) in 2018 (Table:2; Figure: 1). Contrastingly, no change was observed in mortality among patients on ACEi.
The use of any of the three de ned medications increased year-on-year. The use of ACEi, A2RB or diuretics pre-AKI increased from 39.7% in 2016 (n=78), to 59.3% in 2017 (n=86) and 64.6% in 2018 (n=82). Patients presenting to hospital with an AKI-3, on pre-existing ACEi, A2RB or diuretics were more prevalent in number, but upon instigation of treatment tended to have better outcomes. Mortality associated with the use of these medications reduced each year; 32.3% in 2016, 25.5% in 2017 and 18.9% in 2018 (Table:1; Figure: 1).
Data was collected on four co-morbidities commonly associated with AKI-3, the effects of which were analysed. The four co-morbidities under consideration were as follows: hypertension (HTN), Type 1 or Type 2 Diabetes Mellitus (DM), left ventricular failure (LVF), and liver disease (LD). On this analysis, the two more prevalent comorbidities, HTN (47.2%) and DM (31.7%), were also the ones associated with decreased mortality, with relative mortality risk of 0.872 linked with HTN and 0.718 in the diabetic population. Contrastingly, LVF and LD that were the least prevalent co-morbidities (LVF=18.7%, LD=11.4%) was also the ones associated with increased mortality, showing relative risk ratios of 1.33 and 1.44 respectively (Table:1; Table:3).

Discussion
This study aims to analyse the evolution of patient outcomes relating to site-wide service developments over three years. We also aimed to explore a range of factors known to affect clinical outcome among a cohort of AKI patients, such as co-morbidities and medications. Firstly, there was an overall reduction in patient mortality within this study population during the three-year period. Secondly, there was an inverse relationship between percentage of all AKI patients on the de ned medications and mortality. Furthermore, overall patient mortality decreased among those treated with RRT, which proved to be statistically signi cant. Finally, there was a greater incidence of CA-AKI3 and a greater mortality among patients with HA-AKI3.
There was a reduction in incidence of overall mortality among all AKI-3 patients throughout the study period. While this reduction may be attributed to a multitude of factors, it may well also re ect the interventions and service developments made between 2016 and 2018. Similar outcomes have been demonstrated by an epidemiological study on hospitalized patients with AKI in England by Kolhe et al. [15].
Interestingly, our ndings demonstrated an inverse trend across the three years between the percentage of patients that developed AKI on the de ned medications and percentage mortality in this group. This may be a re ection on the improvements in education among primary and secondary care teams, which promoted wider appropriate use of ACEi, A2RB or diuretics in the context of AKI-3.
Despite the yearly decrease of RRT within this cohort, the patients who were not treated with RRT had a higher overall mortality compared to those treated with RRT. This was moreover statistically signi cant (p=0.050), indicating a direct correlation between treatment with RRT and improved survival. The relative risk of mortality of those not treated with RRT was 4.677, showing a signi cant increase in survival rate when RRT was used as part of their treatment. We can explain this result by the presence of signi cant co-morbidity and frailty in patients not treated with RRT.
Additionally, we found a greater overall rate of mortality among HA-AKI3 patients (31.3%), which supports a previous study by Meran et al. showing increased mortality among patients with HA-AKI3 compared to CA-AKI3 [13]. Contrastingly, the incidence of CA-AKI3 was signi cantly higher than that of HA-AKI3 in all three years, which was in accordance with previous studies [14]. There was still a relative yearly decrease in mortality among HA-AKI3 patients, which indicated potential improvements the interventions had on AKI management in a secondary care setting.
Our study has several limitations regarding data collection and statistical signi cance. Firstly, the characteristics of this study are observational and monocentric, which resulted in a lack of a control arm and a smaller study population. The data was gathered retrospectively from an electronic database that was an extension of the hospital's paper-based system. This meant that hospital-based patient information was often inadequate, and quality of clinical notes were often user-dependent. We mediated this through accessing the patient's general practice records for completion. Furthermore, this study was conducted over a brief timeframe of three years, which decreased the number of patients included in the study population and presented an incomplete view of the longitudinal effects of our interventions. Thus, it was anticipated and demonstrated that despite recognizable trends in mortality across the three years, we were unable to nd any statistically signi cant correlations with any of the measured variables. An additional study over a greater number of years with a larger study population will be bene cial to validate the results of this study.

Conclusion
In conclusion, despite the limitations of this study, we can see a bene t from the applied service improvements toward overall patient outcome and survival. This may be a testament to the positive effects of creating an AKI online health pathway tool, educating wider care teams, and providing easier access to specialist physicians. These factors not only enabled early detection of AKI in primary and secondary care, but also promoted improved management through educating on appropriate use of ACEi, A2RB or diuretics. Therefore, this study supports development of in-reach nephrology services to those acute hospital sites where only remote nephrology services can be accessed.