Using Serum Cystatin C in Diagnosis of AKI

A significant proportion of hospitalized and critically ill patients experience acute kidney injury (AKI). Serum creatinine (sCr) is the measurement used to diagnose AKI. However, there are known limitations associated with the use of sCr that affect the timely detection and response to the management of patients with AKI. Those limitations may be overcome with the use of serum cystatin C (sCys) levels. According to Levi Hooper, PharmD, and colleagues, there are few data available on direct comparisons of those biomarkers in AKI diagnoses.

Using Matrix Laboratories and Simbiology (The MathWorks, Natick, Massachusetts), the researchers developed a quantitative systems pharmacology model to simulate the concentration–time profiles of sCr and sCys under varying degrees of AKI across a spectrum of baseline kidney function. Parameters from existing literature and a contemporary sCr and sCys glomerular filtration rate (GFR) equation were used to assess the time to reach AKI diagnostic criteria for both biomarkers.

Analysis results demonstrated that sCys achieved steady-state concentration and met the threshold for AKI diagnosis significantly faster than sCr, with an advantage of 6 to 48 hours depending on the stage of chronic kidney disease (CKD). Sensitivity in detection of GFR reductions was greater with sCys, with the ability to detect AKI within 12 to 14 hours following onset, compared with 12 to 72 hours for sCr. In addition, for sCys the absolute value diagnostic cutoffs were more effective than the threshold based on percentage, providing consistent detection across varying stages of CKD.

In summary, the authors said, “sCys has superior kinetics for early AKI detection compared with sCr, making it a valuable addition to AKI diagnostic protocols, particularly in high-risk populations. Daily monitoring of sCys in patients at risk of AKI would facilitate more timely detection and potentially improve clinical outcomes. Further research should focus on validating sCys diagnostic criteria and integrating it with other biomarkers to enhance AKI management.”

Source: Hooper L, et al. Clin J Am Soc Nephrol. 2025;20(4):477-484. doi:10.2215/CJN.0000000654