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Prescription of renin–angiotensin system blockers and risk of acute kidney injury: a population-based cohort study
  1. Kathryn E Mansfield,
  2. Dorothea Nitsch,
  3. Liam Smeeth,
  4. Krishnan Bhaskaran,
  5. Laurie A Tomlinson
  1. Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK
  1. Correspondence to Dr Kathryn E Mansfield; kathryn.mansfield{at}


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.

  • acute kidney injury
  • angiotensin-converting enzyme inhibitors
  • angiotensin receptor antagonists
  • cohort study
  • renin-angiotensin system

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  • Contributors LAT had the original idea for the study. All authors were involved in the study design. KEM undertook the data management, primary analysis and wrote the first draft. All authors contributed to further drafts and approved the final manuscript. KEM and LAT had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

  • Funding LAT is funded by a Wellcome Trust intermediate clinical fellowship (101143/Z/13/Z). KB is funded by a Wellcome Trust/Royal Society Sir Henry Dale fellowship (107731/Z/15/Z). LS is supported by a Wellcome Trust Senior Research Fellowship in Clinical Science (098504/Z/12/Z).

  • Competing interests None declared.

  • Ethics approval This study was approved by the LSHTM Research Ethics Committee (reference 6536) and by the CPRD Independent Scientific Advisory Committee (ISAC protocol number: 14-208).

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement No additional data are available.

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