What is the role of serum cystatin C in assessing kidney function?

From the Guidelines

Serum cystatin C is a valuable biomarker for assessing kidney function, particularly in individuals with conditions that affect muscle mass or when creatinine-based measurements are less accurate, as recommended by the 2023 guidelines for laboratory analysis in the diagnosis and management of diabetes mellitus 1.

Key Points

• Serum cystatin C is a small protein produced at a constant rate by all nucleated cells, freely filtered by the glomeruli, and almost completely reabsorbed and metabolized by proximal tubular cells.
• Unlike creatinine, cystatin C levels are less influenced by muscle mass, age, gender, or diet, making it particularly valuable for evaluating kidney function in elderly patients, children, individuals with extreme body compositions, or those with muscle-wasting conditions.
• Cystatin C rises earlier in kidney disease progression, potentially allowing for earlier detection of declining renal function.
• It can be used alone or in combination with creatinine in equations to estimate glomerular filtration rate (eGFR), with the combined approach often providing the most accurate assessment, as supported by a recent meta-analysis 1.
• The test requires a simple blood draw and is widely available in clinical laboratories.
• Certain conditions like thyroid dysfunction, inflammation, or corticosteroid use can affect cystatin C levels independently of kidney function, which should be considered when interpreting results.

Clinical Recommendations

• The use of cystatin C is recommended for confirmatory testing in specific circumstances when eGFR based on serum creatinine is less accurate, such as in individuals with low muscle mass 1.
• Cystatin C may also detect kidney dysfunction at an earlier stage than creatinine in people with diabetes, as suggested by recent guidelines 1.
• The combination of serum cystatin C and creatinine has been found to have the least bias in the estimation of GFR in certain patient populations, such as those with cirrhosis 1.
• However, it is essential to consider the potential limitations and variability of cystatin C measurements, as well as the need for further research on its effectiveness and cost-effectiveness in clinical practice, as noted in previous commentaries 1.

From the Research

Role of Serum Cystatin C in Assessing Kidney Function

• Serum cystatin C is a reliable and accurate marker of kidney function across diverse populations 2.
• It is used to confirm the diagnosis of chronic kidney disease (CKD) determined by creatinine-based estimated glomerular filtration rate (eGFR) and to estimate kidney function when accurate eGFR estimates are needed for clinical decision-making 2.
• The 2012 Kidney Disease Improving Global Outcomes (KDIGO) guidelines recommended using cystatin C to estimate kidney function 2.

Advantages of Serum Cystatin C

• Cystatin C is an alternative filtration marker for estimating GFR, and its use can improve the accuracy of GFR estimates, especially in certain clinical subpopulations 3, 4.
• It does not differ by race like creatinine, correlates better with adverse outcomes compared to creatinine, and provides a more accurate eGFR when used in combination with creatinine 4.
• Cystatin C is more sensitive for estimating GFR than serum creatinine when GFR cut-off values are set to 60 (ml/min/1.73 m2) 5.

Clinical Use of Serum Cystatin C

• 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 2.
• The 2021 National Kidney Foundation and American Society of Nephrology Task Force on Reassessing the Inclusion of Race in Diagnosing Kidney Disease report, and the 2024 Kidney Disease Improving Global Outcomes (KDIGO) Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease (CKD), recommend increased use of cystatin C as an alternative and complementary biomarker for kidney function assessment 4.
• Future research is needed to better understand the performance of cystatin C-based eGFR (eGFRcys) relative to creatinine-based eGFR (eGFRcr) and measured glomerular filtration rate (mGFR) in additional diverse cohorts 4.