Estimating the risk of acute kidney injury associated with use of diuretics and renin angiotensin aldosterone system inhibitors: A population based cohort study using the clinical practice research datalink

BMC Nephrol. 2019 Dec 30;20(1):481. doi: 10.1186/s12882-019-1633-2.


Background: The risk of acute kidney injury (AKI) attributable to renin angiotensin aldosterone (RAAS) inhibitors and diuretics remains unclear.

Methods: We conducted a prospective cohort study using the Clinical Practice Research Datalink (2008-2015) linked to Hospital Episode Statistics - Admitted Patient Care and Office for National Statistics mortality data. Patients were included if they had one or more chronic diagnoses requiring medication. Exposed patients had a first ever prescription for RAAS inhibitors/diuretics during the study period. AKI risk associated with exposure was determined by multivariable Cox regression, propensity score-adjusted Cox regression and a prior event rate ratio (PERR) analysis.

Results: One hundred forty thousand nine hundred fifty-two individuals were included. Increased AKI risk in the exposed group was demonstrated in both the multivariable and propensity score-adjusted cox regressions (HR 1.23 (95% CI 1.04-1.45) and HR 1.24 (1.05-1.47) respectively). The PERR analysis provided a similar overall hazard ratio with a wider confidence interval (HR 1.29 (0.94-1.63)). The increased AKI risk in the exposed group was present only in those receiving two or more antihypertensives. Absolute AKI risk was small.

Conclusions: RAAS inhibitors/diuretics result in an increased risk of AKI. The absolute increase in AKI risk is small, however, and needs to be considered in the context of any potential benefits.

Keywords: Acute kidney injury; Diuretics; Renin-angiotension-aldosterone inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury / chemically induced*
  • Acute Kidney Injury / diagnosis
  • Acute Kidney Injury / epidemiology
  • Aged
  • Aged, 80 and over
  • Angiotensin Receptor Antagonists / adverse effects*
  • Angiotensin-Converting Enzyme Inhibitors / adverse effects*
  • Cohort Studies
  • Databases, Factual
  • Diuretics / adverse effects*
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Mineralocorticoid Receptor Antagonists / adverse effects*
  • Population Surveillance / methods
  • Prospective Studies
  • Renin-Angiotensin System / drug effects*
  • Renin-Angiotensin System / physiology
  • Risk Factors


  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Diuretics
  • Mineralocorticoid Receptor Antagonists