Supplementary data for “Comparisons of Staphylococcus aureus infection and other outcomes between users of angiotensin-converting-enzyme inhibitors and angiotensin II receptor blockers: lessons for COVID-19 from a nationwide cohort study”

Additional information regarding study design, baseline cohort characteristics, and results of sensitivity analyses

The seroprevalence of SARS-CoV-2 in patients on haemodialysis.

A new study reports the seroprevalence of SARS-CoV-2 antibodies among a cross-section of patients on haemodialysis and uses these data to estimate seroprevalence in the general US population. Although this study demonstrates the potential of monitoring infectious disease prevalence in dialysis populations, the findings should be interpreted with caution

Diagnosis of acute kidney injury and its association with in-hospital mortality in patients with infective exacerbations of bronchiectasis: cohort study from a UK nationwide database.

BACKGROUND: Many patients with bronchiectasis have recurrent hospitalisations for infective exacerbations. Acute kidney injury (AKI) is known to be associated with increased in-hospital mortality. This study examined the frequency of AKI, associated risk-factors, and the association of AKI with in-hospital mortality among patients with bronchiectasis. METHODS: Anonymised data of patients with non-cystic fibrosis bronchiectasis from the UK Clinical Practice Research Datalink, linked to Hospital Episode Statistics, were used to identify hospitalisations with a primary diagnosis of lower respiratory tract infection (LRTI), from 2004 to 2013. After estimating the proportion of AKI diagnoses, a multivariable logistic regression model was constructed to investigate which background factors were associated with AKI. In-hospital mortality was compared between hospitalisations with and without an AKI diagnosis, with subsequent logistic regression analyses carried out for the association between AKI and in-hospital mortality. RESULTS: Of 7804 hospitalisations due to LRTI observed in 3477 patients with bronchiectasis, 230 hospitalisations involved an AKI diagnosis, an average of 2.9%. However, the percentage increased from less than 2% in 2004 to nearly 5% in 2013. After taking this temporal change into account, AKI was independently associated with older age, male sex, decreased baseline kidney function, previous history of AKI, and a diagnosis of sepsis. In-hospital mortality was 33.0% (76/230) and 6.8% (516/7574), in hospitalisations with and without AKI, respectively (P < 0.001). After adjustment for confounding factors, diagnosis of AKI remained associated with in-hospital mortality (Odds ratio 5.52, 95% confidence interval: 3.62-8.42). CONCLUSIONS: Among people with bronchiectasis hospitalised for infective exacerbations, there is an important subgroup of patients who develop AKI. These patients have substantially increased in-hospital mortality and therefore greater awareness is needed

Pharmacoepidemiology for nephrologists: do proton pump inhibitors cause chronic kidney disease?

Pharmacoepidemiology studies are increasingly used for research into safe prescribing in chronic kidney disease (CKD). Typically, patients prescribed a drug are compared with patients who are not on the drug and outcomes are compared to draw conclusions about the drug effects. This review article aims to provide the reader with a framework to critically appraise such research. A key concern in pharmacoepidemiology studies is confounding, in that patients who have worse health status are prescribed more drugs or different agents and their worse outcomes are attributed to the drugs not the health status. It may be challenging to adjust for this using statistical methods unless a comparison group with a similar health status but who are prescribed a different (comparison) drug(s) is identified. Another challenge in pharmacoepidemiology is outcome misclassification, as people who are more ill engage more often with the health service, leading to earlier diagnosis in people who are frequent attenders. Finally, using replication cohorts with the same methodology in the same type of health system does not ensure that findings are more robust. We use two recent papers that investigated the association of proton pump inhibitor drugs with CKD as a device to review the main pitfalls of pharmacoepidemiology studies and how to attempt to mitigate against potential biases that can occur

Supplementary data for “Comparisons of Staphylococcus aureus infection and other outcomes between users of angiotensin-converting-enzyme inhibitors and angiotensin II receptor blockers: lessons for COVID-19 from a nationwide cohort study”

Additional information regarding study design, baseline cohort characteristics, and results of sensitivity analyses

Chronic kidney disease and cause-specific hospitalisation: a matched cohort study using primary and secondary care patient data.

BACKGROUND: Although chronic kidney disease (CKD) is associated with various outcomes, the burden of each condition for hospital admission is unknown. AIM: To quantify the association between CKD and cause-specific hospitalisation. DESIGN AND SETTING: A matched cohort study in primary care using Clinical Practice Research Datalink linked to Hospital Episode Statistics in England. METHOD: Patients with CKD (estimated glomerular filtration rate <60 mL/min/1.73 m2 for ≥3 months) and a comparison group of patients without known CKD (matched for age, sex, GP, and calendar time) were identified, 2004-2014. Outcomes were hospitalisations with 10 common conditions as the primary admission diagnosis: heart failure; urinary tract infection; pneumonia; acute kidney injury (AKI); myocardial infarction; cerebral infarction; gastrointestinal bleeding; hip fracture; venous thromboembolism; and intracranial bleeding. A difference in the incidence rate of first hospitalisation for each condition was estimated between matched patients with and without CKD. Multivariable Cox regression was used to estimate a relative risk for each outcome. RESULTS: In a cohort of 242 349 pairs of patients, with and without CKD, the rate difference was largest for heart failure at 6.6/1000 person-years (9.7/1000 versus 3.1/1000 person-years in patients with and without CKD, respectively), followed by urinary tract infection at 5.2, pneumonia at 4.4, and AKI at 4.1/1000 person-years. The relative risk was highest for AKI with a fully adjusted hazard ratio of 4.90, 95% confidence interval (CI) = 4.47 to 5.38, followed by heart failure with 1.66, 95% CI = 1.59 to 1.75. CONCLUSION: Hospitalisations for heart failure, infection, and AKI showed strong associations with CKD in absolute and(or) relative terms, suggesting targets for improved preventive care

Risk factors for developing acute kidney injury in older people with diabetes and community-acquired pneumonia: a population-based UK cohort study.

BACKGROUND: Acute kidney injury (AKI) is being increasingly recognised in ageing populations. There are a paucity of data about AKI risk factors among older individuals with diabetes and infections, who are at particularly high risk of AKI. The objective of this study was to evaluate the risk factors for developing acute kidney injury (AKI) amongst older patients with diabetes and community-acquired pneumonia (CAP) in England, and whether the impact of underlying kidney function varied with age. METHODS: This was a population-based retrospective cohort study over 7 years (01/04/2004-31/3/2011) using electronic health records from the Clinical Practice Research Datalink linked to Hospital Episode Statistics. The study population comprised individuals with diabetes aged ≥65 years with CAP. Associations between demographic, lifestyle factors, co-morbidities and medications and development of AKI within 28 days of CAP were explored in a logistic regression model. RESULTS: Among 3471 patients with CAP and complete covariate data, 298 patients developed subsequent AKI. In multivariable analyses, factors found to be independently associated with AKI included: male sex (adjusted odds ratio, aOR: 1.56 95% confidence interval (CI): 1.20-2.04), hypertension (aOR1.36 95% CI 1.01-1.85), being prescribed either angiotensin-converting-enzyme inhibitors or angiotensin-II-receptor-blockers (aOR: 1.59 95% CI: 1.19-2.13), or insulin (aOR: 2.27 95% CI: 1.27-4.05), presence of proteinuria (aOR 1.27 95% CI 0.98-1.63), and low estimated glomerular filtration rate (eGFR). The odds of AKI were more graded amongst older participants aged ≥80 years compared to those of younger age: for eGFR of ≤29 mL/min/1.73m2 (vs 60 ml/min/1.73m2) aOR: 5.51 95% CI 3.28-9.27 and for eGFR 30-59 mL/min/1.73m2 1.96 95% CI 1.30-2.96, whilst any eGFR < 60 ml/min/1.73m2 was associated with approximately 3-fold increase in the odds of AKI amongst younger individuals (p-value for interaction = 0.007). CONCLUSIONS: The identified risk factors should help primary care and hospital providers identify high risk patients in need of urgent management including more intensive monitoring, and prevention of AKI following pneumonia