Acute kidney injury treated with renal replacement therapy and 5-year mortality after myocardial infarction-related cardiogenic shock: a nationwide population-based cohort study

We conducted this nationwide population-based cohort study using data from medical registries in Denmark. The Danish National Health Service provides universal tax-supported health care, guaranteeing free access to general practitioners and hospitals, and partial reimbursement of prescribed medications [13]. The unique 10-digit Danish Civil Personal Registry number, assigned to all Danish citizens at birth and to residents upon immigration, allows unambiguous linkage of registries [14].

We used the Danish National Patient Registry to identify all persons with a first-time admission for MI-related cardiogenic shock from 2005 through 2012. The Danish National Patient Registry contains data on all non-psychiatric hospital admissions since 1977 and on all hospital outpatient specialist clinic and emergency room contacts since 1995 [15]. Each admission is assigned one primary diagnosis code and up to 19 secondary codes classified according to the International Classification of Diseases, 8^th revision (ICD-8) until the end of 1993 and 10^th revision (ICD-10) thereafter [15]. Important components of critical care, including dialysis, treatment with inotropes/vasopressors and mechanical ventilation, have been coded routinely with high validity since 2005 [16]. The study cohort included only patients with first-time MI events, i.e., patients without a previous diagnosis of MI since 1977. The cohort was further restricted to MI patients with cardiogenic shock, defined either by a concurrent diagnosis code of cardiogenic shock and/or by medical treatment with inotropes or vasopressors during the MI admission. Patients treated with inotropes or vasopressors, but without a diagnosis code for cardiogenic shock, were excluded if they had a diagnosis code for septic shock, hypovolemic shock, or shock without further specification during the admission. A flowchart of the inclusion and exclusion criteria is provided in Additional file 1 (Figure e1). The MI admission period was defined as the initial admission for MI, including transfers to other departments and hospitals.

Data on any treatment with acute RRT during the hospitalization was obtained from the Danish National Patient Registry, which provides accurate data on treatment with acute RRT [15]. To restrict the cohort to patients with first-time dialysis related to the MI under study, patients with prior RRT treatment for acute or chronic kidney disease were excluded.

Information on migration and all-cause mortality was obtained through linkage to the Danish Civil Registration System [14]. This registry was established in 1968 and contains information on date of birth, residence, immigration, and vital status, updated daily [14].

We obtained information on causes of death for patients with MI-related cardiogenic shock from the Danish Register of Causes of Death [17]. This registry contains information from all Danish death certificates coded according to the ICD-10 from 1994–2011 [17]. Codes obtained from the Danish Register of Causes of Death are provided in Additional file 1 (Table e1).

We obtained data on date of first chronic dialysis after hospitalization from the Danish National Patient Register [15].

The Danish Civil Registration System was used to obtain data on the gender and age of patients [14]. Data on comorbidities were obtained from the Danish National Patient Registry using primary and secondary inpatient diagnoses and outpatient hospital diagnoses during a fixed period of 10 years preceding the current admission for MI. We included comorbidities that could act as potential risk factors for AKI-RRT and have a potential impact on mortality: congestive heart failure, peripheral vascular disease, cerebrovascular disease, chronic pulmonary disease, hypertension, atrial fibrillation/flutter, venous thromboembolism, chronic kidney disease, liver disease, diabetes, obesity, and cancer. All diagnosis codes used in the study are provided in Additional file 1 (Table e2).

The Danish Health Service Prescription Registry [18] provided information on filled preadmission prescriptions for angiotensin-converting enzyme (ACE) inhibitors, angiotensin-II antagonists, anti-diabetics, and non-steroidal anti-inflammatory drugs (NSAIDs). We identified prescriptions filled within 100 days before the MI admission because most drugs are sold in packages containing no more than 100 tablets. The Danish Health Service Prescription Registry, established in 2004, includes virtually complete individual-level data on all filled prescriptions for reimbursed drugs in Denmark [18].

We defined diabetes mellitus from its diagnosis code or filled prescriptions for anti-diabetic drugs within 100 days before the MI admission (Additional file 1: Table e2) [18]. Coronary arteriography (CAG), percutaneous coronary intervention (PCI), and coronary artery bypass graft (CABG) during admission were identified from procedure codes in the Danish National Patient Registry.

We tabulated patient characteristics for the entire study population and for the cohort of patients surviving until hospital discharge (denoted as hospital survivors), including gender, age group, comorbidity, use of medication, and procedures during admission, according to AKI-RRT status.

We first calculated the in-hospital mortality risk in AKI-RRT and non-AKI-RRT patients for all patients with complete follow-up on their hospitalization for MI, i.e., patients discharged before the end of the study period on 31 December 2012. Next, we computed the propensity score-adjusted relative risk of death during hospitalization, comparing AKI-RRT patients with non-AKI-RRT patients, using a generalized linear model with a log-link function and a binomial error distribution [19, 20]. We used a propensity score in the adjusted analysis to include more variables than a standard multivariate analysis would allow [21]. The propensity score was defined as the probability of developing AKI-RRT during hospitalization conditioned on the observed baseline covariates and computed using a logistic regression model [21]. The covariates included in the propensity score were gender, age group (<60, 60–69, 70–79, ≥80 years), comorbidities (congestive heart failure, peripheral vascular disease, cerebrovascular disease, chronic pulmonary disease, hypertension, atrial fibrillation/flutter, venous thromboembolism, chronic kidney disease, liver disease, diabetes mellitus, cancer, and obesity), use of medications (ACE inhibitors, angiotensin receptor blockers, NSAIDs), and PCI or CABG status. The equal distribution of propensity scores is visualized in Additional file 1 (Figure e2).

We followed hospital survivors for up to 5 years following their hospital discharge date or until death, emigration, or the end of the study period, whichever came first. We used the 1 minus Kaplan-Meier method to compute cumulative mortality following hospital discharge. Crude and propensity score-adjusted hazard ratios were computed using a Cox regression model. The distribution of propensity scores is shown in Additional file 1 (Figure e3).

To examine the potential differential impact of AKI-RRT within subgroups, we repeated the Cox regression analyses stratified by gender, age groups, comorbidity, PCI or CABG status, and subgroups of MI (ST-elevation MI (STEMI), non-STEMI, and unspecified MI). We adjusted for propensity score. The propensity score calculated within each subgroup included the same baseline variables as in the overall propensity score except for the subgroup variable itself [21].

We computed the cumulative risk of chronic dialysis after MI admission by AKI-RRT status accounting for competing risk of death [22]. We visualized the results graphically as a cumulative incidence plot. Crude and propensity score-adjusted hazard ratios were computed with use of a Cox regression model [23].

Proportional hazards assumptions in all of the Cox regression analyses were assessed graphically by plotting log(−log(survival function)) against time for patients with and without AKI-RRT and were found to be satisfactory.

For all MI patients surviving until hospital discharge we tabulated cause of death according to AKI-RRT status. The following causes of immediate death occurred most frequently: cardiovascular disease, kidney disease, pulmonary disease and cancer.

We used STATA statistical software version 13.1 (StataCorp LP, TX, USA) for all statistical analyses. The study was approved by the Danish Data Protection Agency, record number 2014-41-3658. Data in the Danish registries are available to researchers, and their use does not require informed consent or ethics approval.