RAS Inhibition Prior to Admission and Extent of Kidney Injury in Sepsis-Associated AKI

First Author(s)

• 

  Alexander Flannery, PharmD, PhD, BCCCP

  Assistant Professor
  University of Kentucky College of Pharmacy
  Lexington, Kentucky

  Disclosure information not submitted.

  Slides and Audio

Co-Author(s)

• AK

  Adam Kiser, PharmD Candidate

  Pharmacy Student
  University of Kentucky College of Pharmacy, United States

  Disclosure information not submitted.
• 

  Michael Behal, PharmD

  University of Kentucky
  Lexington, Kentucky

  Disclosure information not submitted.
• JN

  Javier Neyra, MD, MSCS

  Associate Professor
  University of Kentucky College of Medicine, United States

  Disclosure information not submitted.

Title: RAS Inhibition Prior to Admission and Extent of Kidney Injury in Sepsis-Associated AKI
 
Introduction/Hypothesis: Sepsis-associated acute kidney injury (SA-AKI) is associated with significant morbidity and mortality. Pre-clinical data support the concept that the angiotensin II type 1 receptor (AT1) is down-regulated in early SA-AKI and impaired AT1 signaling contributes to the pathophysiology in the early stages of SA-AKI. We sought to assess if prior to admission medication use inhibiting the renin-angiotensin system (RASi), defined as angiotensin converting enzyme inhibitors or angiotensin receptor blockers, was associated with more severe SA-AKI.

Methods: Retrospective, single center, cohort study of patients with SA-AKI admitted to the medical intensive care unit (ICU) over a 7-year period. Exclusion criteria included outside hospital transfers, death within 24 hours of admission, end-stage kidney disease, or history of kidney transplant. The primary outcome was stage of AKI on admission per Kidney Disease: Improving Global Outcomes criteria with RASi prior to admission as the exposure of interest. To adjust for potential confounders associated with RASi use prior to admission and SA-AKI on admission, including age, sex, race, comorbidities, and baseline estimated glomerular filtration rate, a multinomial logistic regression model was constructed.

Results: 707 patients with SA-AKI were admitted to the ICU of which 237 (33.5%) were RAS inhibited. Patients with RASi prior to admission had more stage 3 AKI on admission (p=0.008) and were more likely to reach stage 3 AKI within the first week of admission (p=0.047) compared to patients not receiving RASi. Following adjustment for potential confounders, patients with stage 3 AKI on admission were more likely to be receiving RASi prior to admission compared to patients with stage 1 AKI (Relative Risk Ratio 2.32 [1.50-3.59]). There were no differences in mortality, hospital or ICU length of stay, development of acute kidney disease, or requirement for kidney replacement therapy between the RASi and non-RASi cohorts.

Conclusions: RASi prior to admission is associated with more severe kidney injury in SA-AKI. This exacerbation of SA-AKI with chronic use of RASi supports the concept that impaired AT1 signaling drives a component of the pathophysiology of early SA-AKI.