From the Guidelines
A decreased estimated glomerular filtration rate (eGFR) with normal cystatin C levels suggests that the eGFR reduction may not accurately reflect true kidney dysfunction, and clinical decisions should be guided by the patient's overall clinical picture, including other laboratory values, medical history, and physical examination findings. This pattern may indicate that the eGFR reduction is due to factors affecting creatinine levels, such as decreased muscle mass, vegetarian diet, certain medications, or advanced age, rather than actual kidney impairment 1. Cystatin C is considered a more stable biomarker of kidney function than creatinine because it's less affected by muscle mass, diet, age, and gender.
When cystatin C is normal despite a low eGFR, using the combined creatinine-cystatin C eGFR equation may provide a more accurate assessment of kidney function, as recommended by the KDIGO 2024 clinical practice guideline for the evaluation and management of chronic kidney disease 1. The guideline suggests that eGFRcr-cys should be used in clinical situations when eGFRcr is less accurate and GFR affects clinical decision-making.
Key considerations in the interpretation of eGFR and cystatin C levels include:
- Understanding the value and limitations of both eGFR and measured glomerular filtration rate (mGFR) 1
- Recognizing the variability and factors that influence SCr and cystatin C measurements, such as dietary intake 1
- Assessing the potential for error in eGFR when assessing a change in GFR over time 1
- Considering the use of cystatin C–based estimated glomerular filtration rate (eGFRcys) in specific circumstances, as well as the implications of differences between eGFRcr and eGFRcys 1.
Recent commentary on the KDIGO 2024 guidelines highlights the importance of using a combination of markers, including cystatin C and the urinary albumin-creatinine ratio (UACR), to provide a more complete picture of impaired kidney function 1. By considering the patient's overall clinical picture and using a combination of markers, clinicians can make more informed decisions about kidney function and provide optimized care.
From the Research
Deceased eGFR but Normal Cystatin C
- The discrepancy between cystatin C- and creatinine-based estimated glomerular filtration rate (eGFR) is common in patients with heart failure and reduced ejection fraction (HFrEF) 2.
- More negative values of eGFR difference between cystatin C and creatinine (eGFRdiffcysC-Scr) are associated with worse outcomes, including mortality, poor quality of life, and frailty 2.
- Cystatin C has been established as an early and accurate biomarker of chronic kidney disease (CKD) that is particularly helpful in patients for whom creatinine is an inadequate marker 3.
- The intraindividual difference in estimated glomerular filtration rate by creatinine vs cystatin C (eGFRdiffcys-cr) is associated with end-stage kidney disease and mortality among individuals with CKD 4.
- Large differences between eGFRcys and eGFRcr are common in persons with CKD, and these differences and their changes over time may be informative of ESKD and mortality risks 4.
- Cystatin C-based eGFR (eGFRcys) improves GFR estimation in populations with a variety of acute and chronic illnesses, providing indications for cystatin C measurement 5.
Clinical Implications
- The decline in kidney function associated with worsening heart failure is more marked when assessed with eGFRcys than with eGFRScr 2.
- eGFRcr-cys improves GFR estimation in populations with cancer, HIV, and obesity, but does not perform consistently better in cirrhosis, liver transplant, heart failure, neuromuscular disease, and critical illness 5.
- The use of renin-angiotensin system (RAS) inhibitors is standard of care in people with early to moderate CKD, but less is known regarding the efficacy of RAS inhibitors in very advanced CKD 6.