From the Guidelines
Cystatin-C is more specific than creatinine for evaluating renal disease, particularly in detecting early kidney dysfunction and in specific populations such as the elderly, children, and those with reduced muscle mass. While creatinine has been the traditional marker for kidney function, it has several limitations as it's affected by muscle mass, age, sex, and diet 1. Cystatin-C, a protein produced at a constant rate by all nucleated cells, is filtered freely by the glomerulus and not secreted by renal tubules, making it a more accurate reflection of glomerular filtration rate (GFR) 1.
Key Points
- Cystatin-C is particularly valuable in detecting early kidney dysfunction when creatinine may still appear normal 1.
- It's more sensitive in specific populations including the elderly, children, patients with liver disease, and those with reduced muscle mass 1.
- Cystatin-C is also better at predicting progression of kidney disease and cardiovascular outcomes in patients with chronic kidney disease 1.
- However, cystatin-C testing is more expensive and less widely available than creatinine.
Recommendations
- For optimal assessment, many nephrologists now recommend using both markers together in equations that estimate GFR, as this combined approach provides the most accurate evaluation of kidney function across diverse patient populations 1.
- The use of cystatin C, especially to confirm eGFR in adults who are at risk for or have chronic kidney disease, is recommended 1.
- National efforts to facilitate increased, routine, and timely use of cystatin C are also recommended 1.
From the Research
Comparison of Creatinine and Cystatin-C in Evaluating Renal Disease
- Creatinine and cystatin-C are two biomarkers used to evaluate renal function, with cystatin-C being considered a more reliable and accurate marker of kidney function across diverse populations 2.
- The 2012 Kidney Disease Improving Global Outcomes (KDIGO) guidelines recommended using cystatin-C to confirm the diagnosis of chronic kidney disease (CKD) determined by creatinine-based estimated glomerular filtration rate (eGFR) 2.
- A meta-analysis of diagnostic test studies found that serum cystatin C (sCysC) has a high diagnostic accuracy for chronic kidney disease, with a diagnostic odds ratio (DOR) of 40 and an area under the curve for the receiver-operating characteristic (AUROC) of 0.92 3.
Diagnostic Value of Cystatin-C and Creatinine
- A study found that the diagnostic value of sCysC is better than that of serum creatinine (SCr) in evaluating glomerular filtration rate (GFR) in patients with chronic kidney disease, especially when GFR cut-off values are set to 60 (ml/min/1.73 m2) 4.
- Another study found that cystatin C improves estimation of GFR over creatinine alone, but the association between most risk factors and GFR was more accurate by eGFR based on creatinine alone 5.
- The sensitivity and specificity of sCysC in predicting CKD were 0.85 and 0.87, respectively, while the sensitivity and specificity of SCr were 0.77 and 0.91, respectively 4.
Clinical Considerations
- The National Kidney Foundation (NKF) and American Society of Nephrology (ASN) Joint Task Force recommended increasing availability and clinical adoption of cystatin C to assess kidney function, especially in efforts to remove race from eGFR calculations in the United States 2.
- Current research questions are no longer focused on if, but rather when and how often cystatin C should be used in the evaluation of CKD patients, with the transition of all reagents and estimated GFR equations to the newly established International Standard being critical for developing generalizable data 6.