Authors: Lei S et al.
Anesthesiology 144(4):811–822, April 2026
Summary:
This large observational study evaluates the clinical significance of discordance between creatinine-based and cystatin C–based estimates of renal function in surgical patients. Using two large cohorts totaling nearly 59,000 patients undergoing major noncardiac surgery, the authors examined whether differences between these two measurements (eGFRdiff) predict postoperative outcomes.
The study found that a more negative eGFRdiff—where cystatin C suggests worse renal function than creatinine—is consistently associated with a higher risk of postoperative complications and mortality. This relationship was robust across both cohorts and remained significant after adjusting for demographics, comorbidities, surgical factors, and other laboratory values. Importantly, the association extended across multiple complications, including cardiovascular events, acute kidney injury, infections, pulmonary complications, and death.
The magnitude of risk was clinically meaningful, with each 10-unit decrease in eGFRdiff associated with approximately a 10–12% increase in the odds of adverse outcomes. This suggests that eGFRdiff is not just statistically significant, but potentially useful as a real-world risk stratification tool.
The physiologic explanation centers on the limitations of creatinine as a biomarker. Because creatinine is influenced by muscle mass, it may overestimate kidney function in frail or sarcopenic patients. In contrast, cystatin C provides a more accurate reflection of underlying physiologic reserve and systemic stress. Therefore, discordance between the two measurements may identify patients who appear “low risk” by traditional metrics but are actually vulnerable.
While the findings are compelling, the study is limited by its retrospective design and focus on Asian populations, and further validation in broader populations is needed before widespread clinical adoption.
Overall, the study supports eGFRdiff as a novel and practical biomarker that can enhance perioperative risk assessment using routinely available laboratory data.
Key Points:
- Negative eGFRdiff (cystatin C < creatinine) is associated with increased postoperative complications and mortality
- Findings were consistent across two large cohorts (~59,000 patients)
- Risk increases by ~10–12% per 10-unit decrease in eGFRdiff
- Association applies across multiple complications (cardiac, renal, infectious, pulmonary, mortality)
- eGFRdiff may identify high-risk patients missed by traditional creatinine-based assessment
What You Should Know:
This is a simple upgrade to how we interpret labs. The patient with a “normal” creatinine may not be normal at all. If cystatin C tells a different story, believe it. This could help you identify high-risk patients before they declare themselves postoperatively.
We would like to thank Anesthesiology for allowing us to summarize and share this article.