Prescription of renin-angiotensin system blockers and risk of acute kidney injury: a population-based cohort study

Abstract

Objective: To investigate whether there is an association between use of ACE inhibitors (ACEI) and angiotensin receptor blockers (ARB) and risk of acute kidney injury (AKI).

Study design: We conducted a new-user cohort study of the rate of AKI among users of common antihypertensives.

Setting: UK primary care practices contributing to the Clinical Practice Research Datalink (CPRD) eligible for linkage to hospital records data from the Hospital Episode Statistics (HES) database between April 1997 and March 2014.

Participants: New users of antihypertensives: ACEI/ARB, β-blockers, calcium channel blockers and thiazide diuretics.

Outcomes: The outcome was first episode of AKI. We estimated incidence rate ratio (RR) for AKI during time exposed to ACEI/ARB compared to time unexposed, adjusting for age, sex, comorbidities, use of other antihypertensive drugs and calendar period using Poisson regression. Covariates were time updated.

Results: Among 570 445 participants, 303 761 were prescribed ACEI/ARB with a mean follow-up of 4.1 years. The adjusted RR of AKI during time exposed to ACEI/ARB compared to time unexposed was 1.12 (95% CI 1.07 to 1.17). This relative risk varied depending on absolute risk of AKI, with lower or no increased relative risk from the drugs among those at greatest absolute risk. For example, among people with stage 4 chronic kidney disease (who had 6.69 (95% CI 5.57 to 8.03) times higher rate of AKI compared to those without chronic kidney disease), the adjusted RR of AKI during time exposed to ACEI/ARB compared to time unexposed was 0.66 (95% CI 0.44 to 0.97) in contrast to 1.17 (95% CI 1.09 to 1.25) among people without chronic kidney disease.

Conclusions: Treatment with ACEI/ARB is associated with only a small increase in AKI risk while individual patient characteristics are much more strongly associated with the rate of AKI. The degree of increased risk varies between patient groups.

Keywords: acute kidney injury; angiotensin receptor antagonists; angiotensin-converting enzyme inhibitors; cohort study; renin-angiotensin system.

Figure 1

Flow diagram showing the creation of the cohort and reasons for exclusion. ACEI/ARB, ACE inhibitors inhibitor/angiotensin receptor blocker; BB, β blocker; CCB, calcium channel blocker; CPRD, Clinical Practice Research Datalink; HES, Hospital Episode Statistics; ESRD, end-stage renal disease.

Figure 2

Modelled rates* of AKI (during the calendar period 2012–2014) per 1000 person years at risk for AKI during time exposed to antihypertensive treatment including ACEI/ARB compared to time exposed to antihypertensive treatment excluding ACEI/ARB, stratified by characteristics and comorbidities. *Absolute rates (unless otherwise stated) are for men, aged 75–84, with CKD stage 3a, and no comorbidities—chosen as a large, clinically important, high-risk group. **Adjusted using Poisson regression for age, sex, chronic comorbidities (CKD, hypertension, diabetes mellitus, cardiac failure, ischaemic heart disease and arrhythmia), time exposed to other antihypertensive drugs (β blockers, calcium channel blockers and thiazides), time exposed to loop and potassium-sparing diuretics and calendar period. AKI, acute kidney injury; ACEI/ARB, ACE inhibitors inhibitor/angiotensin receptor blocker; pyar, Person years at risk; CKD, chronic kidney disease; ACEI/ARB exposed, antihypertensive treatment including ACEI/ARB; ACEI/ARB unexposed, antihypertensive treatment excluding ACEI/ARB; IRR, incidence rate ratio.