Evaluating the Impact of Leukotriene Receptor Antagonists on Postoperative Acute Kidney Injury: A Retrospective Study

Postoperative acute kidney injury (AKI) is a major complication after oncological surgery, associated with increased morbidity and mortality. Experimental and clinical evidence suggests that leukotriene receptor antagonists, such as montelukast, may reduce inflammation and oxidative stress, potentially protecting against renal injury. In the current study, we investigated the association of perioperative use of leukotriene receptor antagonists and postoperative AKI. Specifically, we hypothesized that leukotriene receptor antagonists, such as montelukast and zafirlukast, would be associated with a lower postoperative incidence of AKI.

This single-center retrospective study included adult patients undergoing oncological surgery between April 1, 2016, and September 30, 2025. The primary endpoint was AKI within 7 days of surgery, defined by Kidney Disease Improving Global Outcomes (KDIGO). Secondary endpoints were 30-day postoperative complications, length of hospital stay, and hospital stay costs. A propensity score-overlap weighting (OW) was applied to balance potential confounders identified through univariate analysis and biological plausibility. After balancing, a Poisson regression model with robust standard errors was used to assess associations with outcomes.

Of the total 45,751 participants, 555 (1.2%) received a leukotriene receptor antagonist. After weighting for overlap, exposure to the leukotriene receptor antagonist was not significantly associated with AKI 7 days after surgery (risk ratio [RR], 0.79; 95% confidence interval [CI], 0.60-1.06; P = .12). The duration of post-anesthesia care unit (PACU) admission was slightly shorter in leucotriene antagonist users (adjusted mean difference of -5.84 minutes; 95% CI, -14.46 to 2.78; P = .184). A statistically significantly longer hospitalization was observed among leukotriene antagonist users, with a mean adjusted difference of 1.55 days (95% CI, 0.86-2.24; P < .001). The use of leukotriene receptor antagonists was also associated with a higher adjusted risk of surgical reintervention at 7 days: 38.37% vs 33.92%, with an adjusted risk difference of 4.45% (95% CI, 0.31-8.59; P = .035). The adjusted readmission risk at 7 days was 3.52% vs 2.02%, with an adjusted risk difference of 1.49% (95% CI, -0.07 to 3.05; P = .061). The adjusted risks of intensive care unit (ICU) admission were 2.96% vs 2.63%, with an adjusted risk difference of 0.32% (95% CI, -1.11 to 1.76; P = .658).

Perioperative use of leukotriene receptor antagonists was not significantly associated with a lower risk of postoperative AKI following oncologic surgery. Further prospective and mechanistic studies are needed to clarify whether leukotriene receptor antagonists exert renoprotective effects in surgical patients.