Definition

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).

Design:

A time-updated, new-user cohort study among people initiating common antihypertensives (ACEI/ARB, beta-blockers, calcium channel blockers and thiazide diuretics) in primary care between April 1997 and March 2014.

Participants:

Adults initiating antihypertensive drug treatment, with at least one year of registration prior to first prescription, identified from UK primary care practices contributing to the Clinical Practice Research Datalink and eligible for linkage to hospital records data from the Hospital Episode Statistics database.

Main outcome measures:

Incidence rate ratio (RR) for first episode of AKI during time exposed to ACEI/ARB compared to time unexposed, estimated using Poisson regression adjusted for age, sex, comorbidities, use of other antihypertensive drugs, and calendar period.

Results:

Among 570,443 participants with a median follow-up of 2.8 years (IQR 0.4 to 7) there were 15,004 first cases of AKI. The overall crude rate of AKI was 6.4/1,000 person years at risk (95% CI 6.30 to 6.50) but varied from 1.63 (1.43 to 1.86) to 662.53 (538.98 to 814.40) depending on, age, comorbidities, and other prescribed drugs. The adjusted RR of AKI during time exposed to ACEI/ARB compared to time unexposed was 1.18 (95% CI 1.13 to 1.23) which was attenuated to 1.12 (95% CI 1.08 to 1.17) after adjustment for non-thiazide diuretic therapy. There was an interaction for the risk of AKI between people using loop diuretics and ACEI/ARB. For those taking loop diuretics, the adjusted RR of AKI during time exposed to ACEI/ARB compared to time unexposed was 0.99 (95% CI 0.92 to 1.06) but it was 1.18 (95% CI 1.13 to 1.24) among people not-exposed to loop diuretics (p<0.001).

Conclusions:

Treatment with ACEI/ARB alone appears to be associated with a small increase in the rate of AKI which is largely seen among people with low absolute risk of AKI. Among people requiring loop diuretics, who have a high absolute risk of AKI, treatment with ACEI/ARB had no measurable association with AKI.

Publications

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