A Protocolized Strategy to Identify Risk Factors for Renal Function Discordance Using Cystatin C

Introduction: Cystatin C (CysC) may more accurately assess renal function in ICU patients, where discordance between serum creatinine (SCr) and CysC is common. Limited data exist on which ICU patients are most at risk and may benefit from incorporating CysC.


Methods: An ICU-wide protocol was developed using standardized criteria to prospectively identify patients at risk for discordance between CysC and SCr. Once identified, a CysC was collected, and renal function estimated using the 2021 CKD-EPI SCr-CysC equation (eGFRSCr-CysC) and compared to SCr based clearance using the Cockcroft-Gault equation (CrCl). Discordance was defined as > 30% difference between CrCl and eGFRSCr-CysC. Ten risk factors for discordance were identified: Age > 65 years, amputation, neuromuscular disease, ICU stay > 7 days, para/quadriplegia, cirrhosis, low urine output, malnutrition/BMI < 18.5, BMI >30, and BUN >40. Patients with AKI greater than stage 1, renal replacement therapy, kidney transplant within 1 year, or if SCr and CysC were drawn > 24 hours apart were excluded. A multivariate logistic regression analysis was performed to identify risk factors associated with discordance between CrCl and eGFRSCr-CysC.


Results: From December 1st, 2024 to March 31st, 2025, 148 patients met criteria, from whom 180 CysC values were obtained. Patients were a median age of 66 years and 57% were male. The median CrCl and eGFRSCr-CysC were 77 (51,122) ml/min and 57 (38,80) ml/min/1.73m2, respectively. Discordance resulting in a higher CrCl compared to eGFRSCr-CysC occurred in 61% of CysC values. In a multivariate regression analysis, ICU stay > 7 days, BMI >30 and BUN >40 were independent positive predictors of discordance, while age > 65 was protective. Each additional risk factor was associated with a nearly two-fold increase in risk of discordance (OR:1.9, 95% CI: 1.3-2.7, p< 0.001). Forty-four percent (N=80) of CysC results led to at least one medication dose adjustment, with antimicrobials accounting for 75% of changes.


Conclusions: In ICU patients, discordance between SCr and Cys C–based renal function estimates is common and clinically impactful, particularly among those with prolonged ICU stays, elevated BMI, and high BUN. Implementing a targeted protocol to identify high-risk patients frequently led to medication dose adjustments.