Which is a better indicator of renal function in athletes, creatinine or cystatin C (Cysteine Proteinase Inhibitor C)?

Cystatin C is a Better Indicator of Renal Function in Athletes Than Creatinine

Cystatin C is superior to creatinine for assessing renal function in athletes due to its independence from muscle mass, providing more accurate glomerular filtration rate estimation in this population.

Why Creatinine is Problematic in Athletes

Creatinine-based measurements have significant limitations when assessing renal function in athletes:

• Creatinine is produced from muscle catabolism, making it highly dependent on muscle mass 1
• Athletes typically have higher muscle mass, which can lead to elevated serum creatinine levels not reflective of actual kidney function
• This can result in underestimation of renal impairment when using creatinine-based equations 2
• In a study of recreational male runners, creatinine increased by 41% after marathon running compared to only 21% for cystatin C, suggesting creatinine is more affected by muscle damage during exercise 2

Advantages of Cystatin C in Athletes

Cystatin C offers several benefits for assessing renal function in athletic populations:

• Produced at a constant rate by all nucleated cells in the body 1
• Not influenced by muscle mass, gender, or age 1, 3
• Less affected by extreme exercise and muscle damage 2
• Provides more reliable GFR estimation in individuals with altered muscle mass 4
• Shows less variance compared to creatinine at different BMI levels in athletes 3

A 2024 study examining men with testosterone-induced muscle hypertrophy (all characterized as competitive or recreational athletes) found that cystatin C measurements displayed less variance compared to creatinine across different BMI categories 3.

Clinical Applications and Recommendations

When assessing renal function in athletes:

1. Use cystatin C-based equations (eGFRcys) as the primary method for GFR estimation 1, 4
2. Consider combined creatinine-cystatin C equations (eGFRcr-cys) for even greater accuracy in some cases 1
3. Recognize that all creatinine-based equations may overestimate GFR in individuals with high muscle mass 4, 5
4. Be aware that renal impairment is common during and after severe exercise, making accurate assessment crucial 2

Important Considerations

• The KDIGO guidelines recommend using the most accurate, validated equations to estimate GFR, preferably with a combination of serum creatinine and cystatin C 1
• For athletes specifically, cystatin C-based equations are more appropriate when increased muscle mass is the primary factor affecting creatinine levels 1
• In a study of patients with neuromuscular disease (opposite condition to athletes), all equations overestimated kidney function, but cystatin C-based estimations performed better than creatinine-based ones 5

Limitations and Caveats

• Cystatin C testing may be more expensive and less widely available than creatinine testing
• Smoking can affect non-GFR determinants of cystatin C 1
• In some clinical contexts like kidney transplantation, the added value of cystatin C for CKD detection may be limited 1

For accurate assessment of renal function in athletes, cystatin C provides a more reliable biomarker that is less influenced by the high muscle mass typical in this population, making it the preferred option for detecting early or subtle changes in kidney function.