Renin-Angiotensin System Blockade after Acute Kidney Injury (AKI) and Risk of Recurrent AKI

Clin J Am Soc Nephrol. 2020 Jan 7;15(1):26-34. doi: 10.2215/CJN.05800519. Epub 2019 Dec 16.

Abstract

Background and objectives: How to best medically manage patients who survived hospitalized AKI is unclear. Use of renin-angiotensin system blockers in this setting may increase risk of recurrent AKI.

Design, setting, participants, & measurements: This is a cohort study of 10,242 members of an integrated health care delivery system in Northern California who experienced AKI and survived a hospitalization between January 1, 2006 and December 31, 2013. All study participants did not have prior heart failure or use of angiotensin-converting enzyme inhibitors (ACE-Is) or angiotensin receptor blockers (ARBs) up to 5 years prior. New receipt and time-updated exposure of ACE-Is/ARBs was identified on the basis of dispensed prescriptions found in outpatient health plan pharmacy databases. The main outcome of interest was subsequent episode of hospitalized AKI after discharge from an initial index hospitalization complicated by AKI. Recurrent AKI episode was defined using acute changes in serum creatinine concentrations. Marginal structural models were used to adjust for baseline and potential time-dependent confounders.

Results: Forty-seven percent of the study population had a documented eGFR<60 ml/min per 1.73 m2 or documented proteinuria before hospitalization. With a median of 3 (interquartile range, 1-5) years of follow-up, 1853 (18%) patients initiated use of ACE-Is/ARBs and 2124 (21%) patients experienced recurrent AKI. Crude rate of recurrent AKI was 6.1 (95% confidence interval [95% CI], 5.9 to 6.4) per 100 person-years off ACE-Is/ARBs and 5.7 (95% CI, 4.9 to 6.5) per 100 person-years on ACE-Is/ARBs. In marginal structural causal inference models that adjusted for baseline and potential time-dependent confounders, exposure to ACE-I/ARB use was not associated with higher incidence of recurrent AKI (adjusted odds ratio, 0.71; 95% CI, 0.45 to 1.12).

Conclusions: In this study of AKI survivors without heart failure, new use of ACE-I/ARB therapy was not independently associated with increased risk of recurrent hospitalized AKI.

Keywords: California; acute kidney injury; acute renal failure; angiotensin receptor antagonists; angiotensin-converting enzyme; creatinine; follow-up studies; heart failture; hospitalization; humans; incidence; odds ratio; outpatients; proteinuria; renin angiotensin system; reninangiotensin system; survivors.

Publication types

  • Observational Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Acute Kidney Injury / blood
  • Acute Kidney Injury / diagnosis
  • Acute Kidney Injury / drug therapy*
  • Acute Kidney Injury / physiopathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Angiotensin Receptor Antagonists / adverse effects
  • Angiotensin Receptor Antagonists / therapeutic use*
  • Angiotensin-Converting Enzyme Inhibitors / adverse effects
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • Biomarkers / blood
  • Creatinine / blood
  • Female
  • Glomerular Filtration Rate
  • Humans
  • Kidney / drug effects*
  • Kidney / physiopathology
  • Male
  • Middle Aged
  • Patient Readmission
  • Recurrence
  • Renin-Angiotensin System / drug effects*
  • Risk Assessment
  • Risk Factors
  • Time Factors
  • Treatment Outcome
  • Young Adult

Substances

  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Biomarkers
  • Creatinine