Acute kidney injury (AKI) remains a major problem for patients undergoing endovascular aortic aneurysm repair (EVAR). It is a postoperative complication with a multifactorial etiology, mainly associated with intraoperative contrast administration, hypovolemia, renal microembolization, complications directly related to renal artery manipulation, lower limb ischemia (ischemia reperfusion syndrome), and multiple other comorbidities typically observed in patients undergoing vascular surgery. All of this have a negative impact on the outcomes of vascular patients, leading to a significant increase in their mortality (De Paulis et al., 2022; Zambetti et al., 2024).

Volatile anesthetics (desflurane and sevoflurane) are commonly used in clinical practice (during induction and maintenance of general anesthesia) (Wang et al., 2021). Previous studies have shown that both desflurane and sevoflurane present organ protection effects (Wu et al., 2014). However, no beneficial effects on perioperative renal function have been reported so far in patients undergoing EVAR.

Volatile anesthetics produce changes in renal function due to their action on the cardiovascular system and the autonomic nervous system (Iguchi et al., 2019; Osborn and Cruz-Lynch, 2021). Some of them can also produce direct renal toxicity due to metabolism (production of inorganic fluoride ions) and degradation processes (production of toxic products, such as compound A, when interacting with carbon dioxide absorbents within the anesthesia circuit) (Kharasch, 2008). Preclinical studies (in rats) (Gonsowski et al., 1994; Obata et al., 2000) have shown nephrotoxicity (renal proximal tubular injury) after administering sevoflurane (under low fresh gas flow conditions), which is directly related to production of compound A. However, it has not been demonstrated that compound A affects human renal function (Conzen et al., 1995; Sondekoppam et al., 2020; Park et al., 2022). A meta-analysis of randomized trials revealed the safety of sevoflurane regarding renal function (Ong Sio et al., 2017). Unlike sevoflurane, degradation of desflurane does not produce component A (Ebert and Arain, 2000).

The aim of this clinical trial was to examine the effects of desflurane or sevoflurane anesthesia on renal function when administered during EVAR, using clinical and biochemical parameters (markers of kidney injury in plasma), before surgery, after surgery, and 24 h postoperatively. We hypothesized that desflurane could be superior to sevoflurane with respect to renal function in patients with aortic aneurysm undergoing endovascular repair.

A total of 80 patients undergoing EVAR completed the study: 40 patients in the desflurane group and 39 in the sevoflurane group suffered from abdominal aortic aneurysm, whereas one patient with thoracic aortic aneurysm was enrolled in the sevoflurane group.

The main result of the present study is that desflurane was associated with a lower plasma NGAL concentration (biomarker of AKI) in patients undergoing EVAR, compared to sevoflurane, as we had previously hypothesized. Both groups (desflurane and sevoflurane) showed a progressive increase in NGAL when comparing the moment before surgery with respect to 24 h postoperatively; however, the sevoflurane group had a higher plasma NGAL concentration than the desflurane group.

Postoperatively, AKI is related with an increased risk of morbidity and mortality (Coca et al., 2012). A recent meta-analysis revealed a lower incidence of AKI with intravenous anesthesia than with volatile anesthesia (Franzén et al., 2023). Based on changes in creatinine and cystatin C, sevoflurane is associated with an increased risk of renal dysfunction after cardiovascular surgery, compared with propofol (Yoo et al., 2014). However, there were no significant differences in plasma creatinine and NGAL measurements between desflurane and propofol (only a significant increase in NGAL was observed between baseline and 2 h postoperatively in the propofol group) (Guerrero-Orriach et al., 2022; Yoon et al., 2025). Therefore, some volatile anesthetic drugs might be more suitable for the kidney than others.

Nowadays, desflurane and sevoflurane are the volatile anesthetics of choice for general anesthesia (Wang et al., 2021). A limited number of studies have investigated the effects of desflurane and sevoflurane on kidney function in patients undergoing surgery, not finding significant differences between the effects of both agents (Kim et al., 2013; Abou Hussein et al., 2015; Karadeniz et al., 2017; Duymaz et al., 2017; Lee et al., 2019; Ebert and Arain, 2000; Ayanoğlu Taş et al., 2022). Among the considerations that could potentially explain these mixed results regarding postoperative kidney function are the small sample size of the studies, the use of standard biomarkers with low sensitivity to detect AKI, and the limited reports on their clinical outcomes.

To our knowledge, this is the first study that has shown the potential association between the intraoperative use of desflurane and a lower increase on a sensitive biomarker of AKI such as NGAL in patients undergoing EVAR, compared to that observed in patients receiving sevoflurane. These results are consistent with those observed in a randomized clinical trial that demonstrated a better postoperative renal function in patients who underwent hepatectomy under general anesthesia with desflurane than those with sevoflurane (Ko et al., 2010). In this study, serum creatinine was significantly higher and the eGFR was significantly lower on the third postoperative day in the sevoflurane group; however, in our clinical trial, these levels of biomarkers did not show significant differences in desflurane versus sevoflurane administration. Serum creatinine is a traditional biomarker used to estimate renal function, which is dependent of glomerular filtration, age, gender, muscle metabolism, diet, treatment, and hydration (Seijas et al., 2014). Another potential disadvantage is that it is not an early biomarker of AKI (a decrease in eGFR of 50% is necessary to produce a noticeable increase in serum creatinine) (Bagshaw and Bellomo, 2007), and in our study, creatinine was only evaluated at 24 h (although perioperative AKI can evolve over 48–72 h). These conditions could explain the different results of the study by Ko JS et al. with respect to the present study regarding postoperative serum creatinine (Ko et al., 2010).

Cystatin C is a biomarker of AKI, which has a higher sensitivity for detection of minor renal damage than creatinine, revealing the onset of renal injury 1 or 2 days earlier compared to creatinine (Herget-Rosenthal et al., 2004; Lisowska-Myjak, 2010). However, an increase in cystatin has also been observed in specific populations such as men, elderly patients, smokers, obese individuals, patients receiving immunosuppressive therapy, and those with thyroid gland disease (Knight et al., 2004). No significant differences were found between desflurane and sevoflurane groups in our study (neither immediately after surgery nor 24 h postoperatively) regarding serum cystatin C and eGFR. There are differences between our findings and those from other authors (Abdelhamid et al., 2013) who showed a significant increase in cystatin 24 h after EVAR surgery; however, this could potentially be explained because the mean of cystatin C was higher in these patients before surgery than the normal range, having not appreciated this difference in our study.

NGAL is a biochemical marker with a high sensitivity and specificity for AKI detection from the very early stages (it increases 2 h after renal injury and 24 h earlier compared to the increase in creatinine). The increase in NGAL indicates tubular damage (Mishra et al., 2005; Wagener et al., 2006; Bennett et al., 2008; Haase et al., 2009; Seijas et al., 2014) and has previously been studied in patients undergoing EVAR (Rampoldi et al., 2018; Karaolanis et al., 2019; Gombert et al., 2019; Stilo et al., 2022). In our study, both desflurane and sevoflurane groups showed a progressive and significant increase in plasma NGAL when comparing the moment before surgery with respect to 24 h after surgery. Registry analyses and clinical trials showed postoperative AKI in patients undergoing EVAR (EVAR Trial Participants, 2005; Hua et al., 2005; Lederle et al., 2009; De Bruin et al., 2013), associated with different mechanisms that included contrast administration (associated with tubular cell toxicity) (Krasinski et al., 2020; Mun et al., 2021). In the present study, there were no significant differences in the amount of contrast medium administered between the desflurane and sevoflurane groups. However, the sevoflurane group showed a higher plasma NGAL concentration than the group anesthetized with desflurane after 24 h of surgery (the linear mixed model for NGAL showed a significant interaction between the two study groups). NGAL is known mainly as a biomarker of AKI, and its levels increase in hypertension, obesity, and diabetes (Romejko et al., 2023). This could influence the outcomes of the present study; however, we did not observe significant differences between groups regarding cardiovascular risk factors (diabetes mellitus, hypertension, and obesity). Although statistically significant (p = 0.03), we do not know the clinical relevance of the NGAL increase (2.15 ng/mL difference between groups). Therefore, this is a potentially indicative study (results may be interpreted as indicative of early tubular damage), requiring replication with a larger sample size and longer follow-up to correlate biomarker elevation with clinical AKI.

We do not know the mechanism that produces this effect; however, compound A (a nephrotoxic metabolite resulting from the degradation of sevoflurane by carbon dioxide absorbents in the anesthesia circuit) could be related to this effect. Laboratory evidence (from animal studies) supports the nephrotoxicity of sevoflurane, but this has not been demonstrated in humans (Gonsowski et al., 1994; Obata et al., 2000). Our study revealed a significant beneficial effect of anesthesia with desflurane compared to sevoflurane regarding renal function; however, future studies are required to investigate the associated mechanisms because a meta-analysis of randomized trials (six studies in humans within clinically relevant exposures, duration of anesthesia > 3 h, and low flow sevoflurane) revealed the safety of sevoflurane regarding maintenance of renal function (Ong Sio et al., 2017).

In our study, the discordance observed between NGAL and KIM-1 demonstrates that NGAL may reflect early stress signals, while KIM-1 increases in response to sustained tubular epithelial damage. In the clinical context, where different factors might affect renal perfusion (hemodynamic fluctuations, volatile anesthetics, and contrast administration), NGAL may have captured early subclinical stress, while KIM-1 might have required more established injury to increase (Yousef Almulhim, 2025).

This study has several limitations. First, in the present clinical trial, even though patients and investigators were blinded to the anesthetic used, it was not possible to blind the responsible anesthesiologist because each volatile anesthetic drug has a different vaporizer that is essential for its administration. Second, animal models have demonstrated an association between sevoflurane, component A, and renal toxicity (Gonsowski et al., 1994; Obata et al., 2000). Therefore, it would have been interesting to measure component A exposures in the present study. Third, NGAL increases rapidly within 2–6 h following renal tubular injury and remains elevated for 18–24 h in patients who develop AKI. Therefore, this early peak makes NGAL a valuable marker in the perioperative setting for detecting tubular injury before changes in serum creatinine or eGFR become evident. This early increase has a predictive value for subsequent clinical AKI in cardiac surgery and critical care patients (Côté et al., 2022; Wagener et al., 2008). This predictive capability supports the use of NGAL as a meaningful early endpoint. Nevertheless, we recognize that the lack of extended follow-up limits our ability to correlate biomarker elevation with clinical AKI. Future investigations with longer follow-up and clinical outcome assessment are needed to confirm the implications of the biomarker changes observed. Finally, this clinical trial was performed to examine the effect of desflurane or sevoflurane anesthesia on renal function when administered in EVAR after 24 h of surgery. Because AKI after EVAR causes increased morbidity and mortality (Zambetti et al., 2024), it would be interesting to follow-up patients over the long term. Future studies will be necessary to respond to this objective.

In our study, desflurane was associated with a lower postoperative AKI than sevoflurane in patients undergoing EVAR. Further research is required to corroborate our results and evaluate their clinical importance.