This is part of my Low eGFR in Athletes series. In this series, I review various components needed to accurately assess kidney function when muscle mass is high.
Creatinine serves as the most common surrogate marker for estimating kidney function. However, the problem with creatinine is that it will be higher for those with high muscle mass and will be lower for those with low muscle mass. This can lead to incorrect estimations of GFR.
Cystatin C provides an alternative marker for estimating kidney function.. But how does Cystatin C differ from creatinine? Let’s dig in.
Today’s key reference is was published in 2023 in the Journal Biomolecules by authors Sebastian Spencer, Robert Desborough and Suil Bhandaro.
What is cystatin C?
All nucleated cells produce cystatin C. Cystatin C distributes throughout the extracellular fluid. In the kidney, the glomeruli filters cystatin C, and the tubules reabsorbs or degrades most of it, excreting very little in the urine
How do you calculate eGFR using Cystatin C?
The National Kidney Foundation eGFR calculator page can calculate eGFR using Cystatin C levels, using the 2012 CKD-EPI Cystatin C equation.
The 2012 CKD-EPI Cystatin C equation to calculate eGFR is:
eGFR = 133 x min(Scys/0.8, 1)-0.499 x max (Scys/0.8, 1)-1.328 x 0.996Age x 0.932 [if female]
Where:
- eGFR (estimated glomerular filtration rate) = mL/min/1.73 m2
- Scys (standardized serum cystatin C) = mg/l
- min = indicates the minimum of Scys/0.8 or 1
- max = indicates the maximum of Scys/0.8 or 1
- age = years
What factors cause Cystatin C to increase?
Aside from the obvious, that kidney disease will cause cystatin levels to increase, other factors include:
- Steroid Treatment
- Cigarette Smoking
- Chronic Inflammation
- Obesity
- Hyperthyroidism
What factors cause Cystatin C to decrease?
The only factors though to decrease cystatin C levels is hypothyroidism.
What are the advantages of using Cystatin C to estimate kidney function?
According to the authors, the keys advantages are:
- not dependent on muscle mass, physical activity or protein intake
- Less influenced than creatinine by age or sex
- Earlier detection of kidney changes compared to creatinine as it rises faster
How do eGFR calculations with Cystatin C compared with measured GFR?
Spencer et al. report that the CKD-EPI equation strongly correlates with measured GFR and shows increased accuracy when both creatinine and cystatin C are used.
| CKD-EPI eGFR (with) | Pearson Correlation (95% Confidence Interval) |
| Creatinine | 0.77 (0.69-0.86) |
| Cystatin | 0.76 (0.68-0.85) |
| Creatinine and Cystatin | 0.81 (0.73-0.89) |
Do eGFR calculations with Cystatin C correlate with outcomes?
Studies suggest that eGFR calculations using Cystatin C are better at predicting health outcomes than eGFR with creatinine. It shows better accuracy at detecting early kidney disease and does better at predicting CVD, kidney failure and death.
Cystatin C also shows particular advantages for specific populations, including:
- Patients with non-white or mixed ethnic backgrounds
- Older age
- Those with frailty or sarcopenia
Take Aways
- Cystatin C is an alternative marker of kidney function and could be useful for helping assess the kidney function of your patient.
- Cystatin C may have particular benefit for some patients when calculations with creatinine alone are difficult to interpret
- An equation that combines both Creatinine and Cystatin C offers a stronger association with understanding adverse health events for patients than using a single marker alone.
But wait, so does that mean that eGFR calculations in athletes with cystatin C will be completely accurate? One to my next post!
