Epidemiology of Acute Kidney Injury in England - 1998 to 2013
Condition: Acute Kidney Injury
MeSH terms: Acute Kidney Injury; Wounds and Injuries
Study type: Observational

Summary: 
      The true population incidence of acute kidney injury (AKI), previously called acute renal
      failure, in England is not known. A better understanding of the epidemiology of AKI at a
      national level is essential to inform initiatives to prevent AKI as well as reduce the
      associated morbidity and mortality. The purpose of this study is to combine the national
      database of all hospital discharges with national census data to investigate trends in the
      incidence of both, AKI not requiring dialysis and AKI requiring dialysis, as well as its
      associated mortality and its determinants in England between 1998 and 2013
    

Detailed description: 
      Subject Selection and Withdrawal We will identify all cases of AKI by using validated
      International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM)
      codes in any of he diagnoses codes, in keeping with the objective of the study. Patients with
      any of the following codes will be included: N17.0 for acute renal failure with tubular
      necrosis, N17.1 for acute renal failure with acute cortical necrosis, N17.2 for acute renal
      failure with medullary necrosis, N17.8 for other acute renal failure and N17.9 for acute
      renal failure, unspecified. Acute renal failure has been replaced by new terminology, acute
      kidney injury, but due to lack of ICD-10-CM codes for AKI, we will use the ICD-10-CM codes
      for acute renal failure and henceforth, will be referred to as AKI in this protocol.

      Subject Recruitment and Screening We will extract 1998 to 2013 data from the Hospital Episode
      Statistics (HES), a data warehouse containing details of all admissions, outpatient
      appointments and A&E attendances at National Health Service (NHS) hospitals in England. HES
      collects a detailed record for each 'episode' of admitted patient care delivered in England,
      either by NHS hospitals, primary care trusts, mental health trusts or delivered in the
      independent sector but commissioned by the NHS. These data are collected during a patient's
      time in hospital and stored as a large collection of separate records, one for each period of
      care, in a secure data warehouse. We will extract secondary diagnosis codes for up to 14
      diagnoses available till 2006-07 and up to 20 additional diagnoses from 2007 till 2013. In
      addition to demographic data, we will also extract up to 15 procedure codes. To identify AKI
      patients requiring dialysis, we will include procedure code of X40.3 for hemodialysis or
      X40.4 for hemofiltration in any of the 15 procedures. To exclude patients with chronic kidney
      disease starting dialysis, we will exclude patients who had chronic kidney disease (CKD)
      stage 5 (N18.5) and end stage renal disease (N18.6) and procedure codes for arteriovenous
      fistula (L74.2) or arteriovenous shunt (L74.3) during the inpatient admission (figure 1).
      This algorithm has been shown to be sensitive and specific, with a high positive and negative
      predictive value (all >90%. Patients who were admitted, but were not discharged during the
      study period will not be included in the study.

      We will obtain data on patient demographics, hospital characteristics, in-hospital mortality,
      disposition, length of stay (LOS), and up to 20 diagnosis and 15 procedure codes that are
      based on the ICD-10-CM and Office of Population Censuses and Surveys Classification of
      Surgical Operations and Procedures, 4th revision (OPCS-4) from the HES database. To obtain
      population incidence of AKI requiring dialysis, we will obtain mid-year populations of
      England in each year from 1998 to 2013 from the Office of National Statistics (ONS). We will
      also obtain length of stay and mortality for all patients who did not have acute kidney
      injury coded as N17 in any of the diagnoses codes, in England over the same time period.

      Patients will not be contacted. This study will not obtain informed consent from the
      patients' as we will be working with anonymous patient data. No screening requirements
      (laboratory or diagnostic testing) are necessary to meet the inclusion or exclusion criteria.
      Unique Subject Identification numbers are already allocated to the patients and the HES
      database does not include any patient's name or hospital number.

      Sample Size Determination The data from HES will be extracted for the period between April
      1998 and March 2013. HES data is collected during a patients' time at hospital and is
      submitted to allow hospitals to be paid for the care they deliver. As this is a retrospective
      population cohort study using a national database, all cases of AKI as defined by the
      inclusion criteria, from the HES database will be used.

      Statistical Methods All analyses will be performed using validated statistical software. Data
      during the 15-year period will be divided into three 5-yr periods (April 1988 to March 2003,
      April 2003 to March 2008 and April 2008 to March 2013) and also presented by individual year.
      Age will be categorized into the groups <65, 65-74, 75-84 and>85. Charlson scores greater
      than 5 will be grouped into one category. Method of admission will be defined as one of
      elective admission; emergency admission; maternity admission; other admission or unknown.
      Ethnicity will be grouped as White, Mixed, Asian, Black, other ethnic groups and ethnicity
      not stated/unknown.

      Continuous variables will be expressed as mean with 95% confidence interval (CI). Categorical
      variables will be expressed as proportions and compared with the chi square test. Incidence
      rates per 1000 person-years and 95% confidence intervals will be calculated using Poisson
      regression analysis and compared using a chi-squared test for proportions. Age-adjusted
      incidence rates for AKI will be calculated based on the UK standard population using the
      direct standardization method. Further analysis will be done to identify regional variation
      in epidemiology of both AKI not requiring dialysis and AKI requiring dialysis in England.

      The Poisson regression model will be used to analyse the effect of gender, age group, period
      of admission, method of admission, Charlson co-morbidity index and ethnicity on incidence of
      AKI. Cox Proportional Hazard Models will be applied to test the association between mortality
      and these variables. Multivariable logistic regression will be considered to assess the
      association between AKI and all these variables simultaneously. We will use the middle period
      of 2003-2008 as reference, which will enable us to evaluate improvement in mortality as
      compared to 1998-2003 and also to evaluate whether the improvement has been sustained in the
      later period of 2008-2013. The effect of AKI on mortality and length of stay will be tested
      using the Cox Proportional Hazard Models and the Linear Regression respectively. Long-term
      survival of patients will be plotted using Kaplan Meir curves after obtaining the date and
      cause of death for all patients obtained from Office of National Statistics.

      We will randomly select a number of patients who had a recorded diagnosis of AKI in HES
      database since 1998. Controls will also be selected and matched to each patient by age, sex,
      date of diagnosis and region. The association between AKI and each exposure will be analyzed
      using conditional logistic regression.

      Data Handling and Record Keeping The data obtained from HES will be anonymised and will not
      have any patient identifiable characteristics. The study protocol, documentation, data and
      all other information generated will be held in strict confidence. No information concerning
      the study or the data will be released to any unauthorized third party, without prior written
      approval of the sponsoring institution. Authorized representatives of the sponsoring
      institution may inspect all documents and records, required to be maintained, by the
      Investigator, including but not limited to, medical records (office, clinic or hospital) for
      the subjects in this study. The clinical study site will permit access to such records.
      Information about study subjects will be kept confidential and managed according to the
      requirements of the Data Protection Act, NHS Caldicott Guardian, The Research Governance
      Framework for Health and Social Care, Ethics Committee Approval and Trust IM&T Policy. The
      Chief/Principal Investigator will be the "Custodian" of the data

      Source Documents The source document will be the HES database. HES data is held as financial
      year data-sets, although the source data is collected monthly from NHS - and originates from
      commissioning messages sent by healthcare providers to healthcare commissioners via the
      secondary User Services (SUS). At pre-arranged date during the year, SUS takes an extract
      from their database and sends it to HES. HES then validates and clean the extract, before
      deriving new items and making the information available in the data warehouse. Data quality
      reports and checks are completed at various stages in the cleaning and processing cycle.

      Records Retention The data will be kept for 15 years after the completion of the study, in
      accordance with the requirements of the Therapeutic Goods Administration and Health Privacy
      Principals.

      All research data and study related documents will be stored, following the end of the study.
      The data will be secured in password-protected computer with access to the chief
      investigator. The data will be deleted from the hard drive of the computer at the end of the
      archival period.

      Study Monitoring, Auditing, and Inspecting The investigator will permit study-related
      monitoring, audits and inspections by the Ethics Committee, the Sponsor and the Research
      Governance Manager. This study will be monitored by the Research Governance Manager according
      to the Research & Development Office procedure for monitoring all non-commercial research
      carried out at the Derby Hospitals NHS Foundation Trust and the Southern Derbyshire Primary
      Care Trusts. In line with the responsibilities set out in the Research Governance Framework,
      the Investigator will ensure that the research governance manager or other regulatory
      monitoring authority is given access to all study-related documents and study related
      facilities.
    

Observational model: Cohort
Time perspective: Retrospective
Sampling method: Non-Probability Sample
Study population: 
        This is a historical cohort study using already collected data from the Hospital Episode
        Statistics (HES), a data warehouse containing details of all admissions, outpatient
        appointments and A&E attendances at NHS hospitals in England.
      
Keywords: acute kidney injury; epidemiology; mortality