Creatinine in Cardiac Critical Care – An Old Marker under a New Lens!

Dear Editor,

Serum creatinine (SCr), though a long-standing biomarker for diagnosing acute kidney injury (AKI), may not fully capture the renal risk profile in cardiac surgical patients. This letter highlights the need for procedure-specific AKI thresholds and predictive tools better aligned with the cardiac surgical setting, moving beyond the traditional “one-size-fits-all” approach.

In a recent large-scale study involving 37,706 patients undergoing coronary artery bypass grafting, Zeng et al. (2024) found that using the Kidney Disease: Improving Global Outcomes (KDIGO)-recommended ≥0.3 mg/dL increase in SCr within 48 h post-surgery did not correlate with a significant rise in 30-day mortality.^[1] In contrast, a higher post-operative SCr cutoff of ≥0.55 mg/ dL – equivalent to 1.83 times the current KDIGO criterion – exhibited a superior predictive value for 30-day mortality. This revised threshold not only improved prognostic accuracy (adjusted odds ratio [OR]: 6.25; 95% confidence interval [CI]: 4.45–8.79; P < 0.001) but also curtailed the rate of potentially inflated AKI diagnoses.^[1]

It is interesting to note that an earlier work from Lassnigg et al. hinted that even minor elevation in post-operative SCr levels could serve as an independent predictor of mortality in patients undergoing cardiothoracic surgery.^[2] Among patients with a post-operative creatinine rise of 0–0.5 mg/dL, the 30-day mortality stood at 6%, which escalated fivefold when the rise exceeded 0.5 mg/dL. This sharp mortality gradient highlights the prognostic amplification associated with even minimal creatinine shifts, in accordance with the cut-off outlined by Zeng et al.^[1,2]

Underlying this complexity is the wide variability in the reported incidence of cardiac surgery-associated AKI (CSA-AKI), ranging from 5% to 42%.^[3] This heterogeneity likely reflects not only procedural differences but also potential inconsistencies emerging from diagnostic criteria, patient factors, and perioperative exposures.

Of note, a comprehensive consensus statement by Brown et al. (2023) provided 13 perioperative recommendations for managing CSA-AKI.^[4] The authors underscore the complex etiology of AKI in cardiac surgical patients – driven by cardiopulmonary bypass, hemodilution, and fluid shifts – and emphasize that the relationship between CSA-AKI and long-term adverse outcomes may be multifactorial.

To refine perioperative risk assessment, several AKI prediction models, including the Cleveland Clinic and Mehta scores, combine clinical and procedural factors.^[5,6] Emerging composite indices that integrate hemodynamic, biochemical, and intraoperative variables, along with biomarker-based scores using urinary neutrophil gelatinase-associated lipocalin (NGAL) and plasma cystatin C, provide improved accuracy for predicting severe or persistent AKI beyond creatinine-based definitions.^[7-9]

In a subgroup analysis of 42,446 intensive care unit (ICU) patients, Pfortmueller et al. found that KDIGO stage 1 AKI predicted 1-year mortality in non-cardiac surgical patients (OR 1.66; 95% CI: 1.45–1.89; P < 0.001), but this association was not significant after cardiac surgery adjustment (OR 1.36; 95% CI: 0.88–2.11; P = 0.2).^[10] These observations lend weight to the view that standardized AKI definitions may fall short in reflecting the distinctive risk profiles of cardiac surgical patients, thereby strengthening the case for a more specific diagnostic criterion.

This raises the need to explore the modification of AKI diagnostic thresholds – anchored in a balance between diagnostic precision and prognostic importance – to better align with the specific context of cardiac surgical care. Integrating novel biomarkers such as creatine, NGAL, or urinary tissue inhibitor of metalloproteinase-2/ insulin-like growth factor binding protein 7 may further enhance outcome prediction and guide perioperative management in the cardiac ICU.^[4]