Authors: Potnuru P et al.
Anesthesiology 144(4):756–758, April 2026
Summary:
This editorial highlights a novel approach to improving preoperative risk stratification by examining the difference between two commonly used estimates of kidney function: creatinine-based eGFR and cystatin C–based eGFR. The authors focus on the concept of “eGFRdiff” (eGFRcys − eGFRcr), which captures discordance between these two measures and reveals important physiologic insights not apparent with standard testing alone.
Using data from a large dual-cohort study of more than 58,000 patients, the referenced research demonstrates that a negative eGFRdiff—where cystatin C suggests worse renal function than creatinine—strongly correlates with increased postoperative complications, including acute kidney injury, cardiovascular events, infections, pulmonary complications, and mortality. Notably, this marker outperformed many traditional predictors, including age, ASA status, and common comorbidities.
The underlying mechanism centers on frailty. Creatinine levels are heavily influenced by muscle mass, meaning that patients with sarcopenia or reduced physiologic reserve may appear to have “normal” kidney function when assessed by creatinine alone. In contrast, cystatin C is less dependent on muscle mass and more reflective of true physiologic stress and inflammation. A large negative eGFRdiff therefore identifies patients whose apparent health is misleading—flagging a high-risk population that would otherwise go unrecognized.
The study’s strengths include its large sample size, external validation, and sophisticated modeling that captures nonlinear relationships between renal function discordance and outcomes. However, the authors emphasize that this remains an association study, and further work is needed to validate eGFRdiff as a predictive tool and integrate it into existing perioperative risk models.
Ultimately, the article frames eGFRdiff as a simple but powerful way to extract more meaningful information from routine lab data, potentially improving identification of high-risk patients before surgery.
Key Points:
- eGFRdiff (cystatin C – creatinine) is strongly associated with postoperative complications and mortality
- Negative eGFRdiff identifies patients with hidden frailty and reduced physiologic reserve
- This marker outperforms many traditional risk factors in predicting outcomes
- Creatinine alone may overestimate kidney function in sarcopenic or frail patients
- Further validation is needed before routine clinical adoption
What You Should Know:
This is a big deal because it uses labs you already have to uncover risk you’re currently missing. The patient who “looks fine” on creatinine may actually be your highest-risk case. This could change how we risk-stratify patients—especially the elderly and frail—without adding cost or complexity.
We would like to thank Anesthesiology for allowing us to summarize and share this article.