The kidneys filter waste and excess fluid from the blood, a function quantified by the Glomerular Filtration Rate (GFR). Directly measuring the true GFR is invasive and impractical for routine medical care. Instead, healthcare professionals rely on a simple blood test and a mathematical calculation to determine the estimated GFR (eGFR), providing a highly effective, non-invasive assessment of kidney function. This calculation uses the concentration of a specific waste product in the blood, along with patient demographic data, to estimate kidney filtration.
Creatinine: The Body’s Filtration Marker
Creatinine is a natural waste product generated from the metabolism of muscle tissue and the breakdown of dietary protein. It is produced at a relatively consistent rate, which is directly proportional to a person’s total muscle mass.
Healthy kidneys efficiently filter this creatinine from the bloodstream, passing it out of the body through the urine. When the kidneys begin to fail, they become less effective at this filtration process, causing creatinine to accumulate in the blood. An elevated level of creatinine in a blood test signals a potential reduction in kidney function.
However, a rise in blood creatinine is considered a late indicator, often not becoming noticeable until a significant portion of kidney function has already been lost. Therefore, simply measuring the raw creatinine level is not sufficient, which is why mathematical formulas were developed to provide a more sensitive assessment.
How Formulas Estimate Kidney Function (eGFR)
The eGFR is a calculation that takes the serum creatinine value and adjusts it using patient-specific characteristics to account for non-kidney factors that influence creatinine levels. The most widely used modern calculations are the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and the older Modification of Diet in Renal Disease (MDRD) study equation.
These equations use the raw creatinine concentration alongside variables such as age and sex to predict the filtration rate. These demographic adjustments are necessary because creatinine production is tied to muscle mass, which generally differs between men and women and decreases with age.
The CKD-EPI equation is now the preferred method, generally performing better than the MDRD equation, particularly for eGFR values above \(60 \text{ mL/min/1.73m}^2\). The 2021 CKD-EPI equation removed the race variable to improve accuracy and address health equity concerns. The final eGFR result is standardized to a typical body surface area of \(1.73 \text{ m}^2\), allowing for consistent comparison across different body sizes.
Decoding Your Estimated GFR Results
The output of the creatinine-based formula is the eGFR, reported in units of \(\text{mL/min/1.73m}^2\). This value represents the volume of fluid the kidneys filter each minute, standardized for body size. For an adult, an eGFR of \(90\) or higher is generally considered to be in the normal range, indicating healthy kidney function.
A persistent eGFR below \(60 \text{ mL/min/1.73m}^2\) for three months or more is the primary clinical definition used to diagnose Chronic Kidney Disease (CKD). CKD is classified into five stages based on the severity of the eGFR value:
- Stage G1 is defined as an eGFR of \(90\) or above, but with other signs of kidney damage present, such as protein in the urine.
- Stage G2 is the \(60\) to \(89 \text{ mL/min/1.73m}^2\) range, suggesting a mildly reduced function.
- Stage G3 is split into two sub-stages: G3a (\(45\) to \(59 \text{ mL/min/1.73m}^2\)) and G3b (\(30\) to \(44 \text{ mL/min/1.73m}^2\)).
- Stage G4 is marked by severe loss of function, with an eGFR between \(15\) and \(29 \text{ mL/min/1.73m}^2\).
- Stage G5, or kidney failure, is reached when the eGFR drops below \(15 \text{ mL/min/1.73m}^2\).
Limitations and External Factors Affecting Accuracy
The eGFR’s accuracy can be compromised by factors unrelated to actual kidney health. Because creatinine production is dependent on muscle mass, individuals with extremes of body size or muscle development may have misleading results. For instance, a bodybuilder with high muscle mass may have an artificially low eGFR, while a frail elderly person or an amputee with low muscle mass may have a falsely high eGFR.
Dietary habits can temporarily affect the result, as consuming large amounts of cooked meat shortly before the test can transiently increase creatinine levels. Certain medications, such as the antibiotic trimethoprim, can interfere with the kidneys’ ability to secrete creatinine into the urine, causing the blood level to rise independently of the actual filtration rate. These formulas are most reliable when kidney function is stable and can be inaccurate in cases of acute kidney injury or in critically ill patients.
When non-filtration factors are expected to distort the creatinine result, clinicians may turn to alternative markers. Cystatin C, a protein less affected by muscle mass, is often combined with creatinine in formulas for a more precise estimation. For complex cases, a direct measurement of GFR using an injected external filtration marker may be necessary, although this procedure is typically reserved for specific clinical decisions.