Preoperative renin-angiotensin system inhibitor management and acute kidney injury after cardiac surgery: a systematic review and meta-analysis

The optimal management of renin-angiotensin system inhibitors (RASIs) before cardiac surgery remains uncertain. Recommendations regarding continuation and preoperative temporary withholding and discontinuation differ, and the comparative effects of specific withdrawal timings on postoperative Acute Kidney Injury (AKI) have not been well established. We conducted a systematic review and meta-analysis to assess the association of preoperative RASI exposure and preoperative RASI management strategies with postoperative AKI and other clinically relevant outcomes after adult cardiac surgery. We searched PubMed, Embase, Web of Science, and the Cochrane Library from inception to 24 July 2025. We included randomized clinical trials and cohort studies of adults undergoing cardiac surgery that evaluated preoperative RASI exposure or compared specific RASI management strategies. The primary outcome was postoperative AKI as defined by the original studies. Secondary outcomes were short-term all-cause mortality and dialysis requirement. Pairwise meta-analysis was conducted separately for randomized and observational evidence. Bayesian/frequentist network meta-analyses (NMA) were used to compare continuation, withdrawal 24 h or 48 h before surgery, or withdrawal on the morning of surgery. Certainty of evidence was assessed using the Confidence in Network Meta-Analysis (CINeMA) framework. Twenty-five studies involving 79,627 patients were included. In observational studies, preoperative RASI exposure was not associated with a statistically significant difference in postoperative AKI [pooled adjusted odds ratio (OR), 0.90; 95% CI, 0.67–1.20], whereas it was associated with lower short-term all-cause mortality (pooled adjusted OR, 0.77; 95% CI, 0.61–0.98), despite substantial heterogeneity. Randomized evidence was sparse and did not permit robust conclusions. In the random-effects NMA, no comparison among continuation and withdrawal strategies provided statistically conclusive evidence of a difference in AKI or mortality. Ranking and fixed-effects models revealed a higher probability of benefit of withdrawal on the morning of surgery. However, these results should be interpreted cautiously because the network was sparse and most comparisons were supported by low or very low certainty evidence. Among adults undergoing cardiac surgery, current evidence does not establish that either continuation or a specific preoperative RASI withdrawal strategy is superior for preventing postoperative AKI or mortality. The predominance of observational evidence, heterogeneity in outcome definitions and treatment strategies, and low certainty of evidence preclude firm clinical recommendations. Adequately powered randomized trials comparing prespecified withdrawal intervals in chronic RASI users are needed. PROSPERO CRD42024557912.