Preoperative angiotensin-converting enzyme inhibitors and angiotensin receptor blocker use and acute kidney injury in patients undergoing cardiac surgery

Abstract

Background: Using either an angiotensin-converting enzyme inhibitor (ACEi) or an angiotensin receptor blocker (ARB) the morning of surgery may lead to 'functional' postoperative acute kidney injury (AKI), measured by an abrupt increase in serum creatinine. Whether the same is true for 'structural' AKI, measured with new urinary biomarkers, is unknown.

Methods: The TRIBE-AKI study was a prospective cohort study of 1594 adults undergoing cardiac surgery at six hospitals between July 2007 and December 2010. We classified the degree of exposure to ACEi/ARB into three categories: 'none' (no exposure prior to surgery), 'held' (on chronic ACEi/ARB but held on the morning of surgery) or 'continued' (on chronic ACEi/ARB and taken the morning of surgery). The co-primary outcomes were 'functional' AKI based upon changes in pre- to postoperative serum creatinine, and 'structural AKI', based upon peak postoperative levels of four urinary biomarkers of kidney injury.

Results: Across the three levels (none, held and continued) of ACEi/ARB exposure there was a graded increase in functional AKI, as defined by AKI stage 1 or worse; (31, 34 and 42%, P for trend 0.03) and by percentage change in serum creatinine from pre- to postoperative (25, 26 and 30%, P for trend 0.03). In contrast, there were no differences in structural AKI across the strata of ACEi/ARB exposure, as assessed by four structural AKI biomarkers (neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, interleukin-18 or liver-fatty acid-binding protein).

Conclusions: Preoperative ACEi/ARB usage was associated with functional but not structural acute kidney injury. As AKI from ACEi/ARB in this setting is unclear, interventional studies testing different strategies of perioperative ACEi/ARB use are warranted.

Keywords: acute renal failure; biomarkers; serum creatinine.

FIGURE 1:

Participant selection.

FIGURE 2:

Incidence of AKI by ACEi/ARB status. (A) Serum creatinine-based definitions of AKI. *P for trend = 0.005; # P for trend = 0.41. (B) Biomarker-based definitions of AKI (5th Quintile of Peak Postoperative Concentration). P for trend not significant for all biomarkers. IL-18, interleukin-18; NGAL, neutrophil gelatinase-associated lipocalin, KIM-1, kidney injury molecule-1; L-FABP, liver-fatty acid binding protein.

FIGURE 3:

Mean and IQR of kidney biomarkers across strata of ACEi/ARB exposure. P values: NGAL 0.94, IL-18 0.09, KIM-1 0.17, L-FABP 0.78. IL-18, interleukin-18; NGAL, neutrophil gelatinase-associated lipocalin, KIM-1, kidney injury molecule-1; L-FABP, liver-fatty acid binding protein.