The Glomerular Filtration Rate (GFR), how it is measured, and the estimated glomerular filtration rate (eGFR)
The glomerular filtration rate (GFR) is a measure of how well the kidneys are filtering waste products from the blood. It is an important indicator of kidney function and is used to diagnose and monitor a range of kidney diseases.
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What is Glomerular Filtration Rate (GFR)?
The kidneys play a vital role in maintaining homeostasis by filtering blood to remove waste products, excess electrolytes, and water, which are excreted as urine. This filtration process occurs in the glomeruli, a network of small blood vessels located within the nephrons, the functional units of the kidney. The glomerular filtration rate (GFR) is a measurement of the amount of blood filtered through the glomeruli per minute, and it serves as a reflection of overall kidney health.
A normal GFR in a healthy adult is about 90 to 120 mL/min/1.73 m², depending on factors such as age, sex, and body size. A decrease in GFR suggests impaired kidney function, as the kidneys are no longer filtering blood as efficiently. GFR tends to decline naturally with age, but a significantly reduced GFR may indicate kidney disease
Values of Glomerular Filtration Rate (GFR)
The GFR is measured in units of mL/min/1.73m2, which takes into account the person's body surface area.
The normal GFR range is generally considered to be between 90 and 120 mL/min/1.73m2. A GFR below 60 mL/min/1.73m2 for more than 3 months is an indication of chronic kidney disease (CKD). CKD is classified into stages based on the GFR values, as follows:
Stage 1: GFR ≥ 90 mL/min/1.73 m² (Normal kidney function but with evidence of kidney damage, such as protein in the urine).
Stage 2: GFR 60-89 mL/min/1.73 m² (Mild decrease in kidney function with evidence of kidney damage).
Stage 3a: GFR 45-59 mL/min/1.73 m² (Mild to moderate decrease in kidney function).
Stage 3b: GFR 30-44 mL/min/1.73 m² (Moderate to severe decrease in kidney function).
Stage 4: GFR 15-29 mL/min/1.73 m² (Severe decrease in kidney function).
Stage 5: GFR < 15 mL/min/1.73 m² (End-stage renal disease, requiring dialysis or a kidney transplant).
It is important to note that GFR values can vary depending on age, gender, race, muscle mass, and other factors. Additionally, GFR should be interpreted in the context of other clinical and laboratory parameters, including serum creatinine levels, urine output, proteinuria, and electrolyte levels.
How is GFR Measured?
Direct measurement of GFR is challenging because it requires the use of special substances that are filtered by the kidneys but not reabsorbed or secreted. As a result, estimated GFR (eGFR) is commonly used in clinical practice. This estimate is derived from equations that use serum creatinine levels, a waste product generated by muscle metabolism, along with patient factors such as age, sex, body size, and ethnicity.
1. Serum Creatinine and eGFR
Serum Creatinine: Creatinine is a byproduct of muscle breakdown that is normally filtered by the kidneys and excreted in urine. Higher levels of creatinine in the blood can indicate reduced kidney function, as the kidneys are not adequately filtering and eliminating it.
eGFR Equations: The most widely used formulas for estimating GFR are the Modification of Diet in Renal Disease (MDRD) formula and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.
2. Cystatin C
In some cases, cystatin C, a protein that is filtered solely by the kidneys, may be used as an alternative to creatinine for estimating GFR. Cystatin C levels are less influenced by factors such as muscle mass, making it a useful tool in populations where creatinine-based estimations may be less reliable, such as in the elderly, malnourished individuals, or people with extreme muscle mass.
3. Direct Measurement of GFR
Although rarely performed in routine clinical practice, GFR can be directly measured using exogenous filtration markers like inulin or radioisotopes (e.g., iothalamate or iohexol). These substances are injected into the bloodstream, and their rate of clearance through the kidneys is measured. While this method provides a more precise measure of GFR, it is time-consuming, expensive, and requires specialized facilities, making it impractical for routine use.
The Modification of Diet in Renal Disease (MDRD) equation
The Modification of Diet in Renal Disease (MDRD) equation is a formula used to estimate the glomerular filtration rate (GFR) based on the level of creatinine in the blood, the age, sex, and race of the person, and other factors that may affect kidney function. The MDRD equation is one of the most commonly used formulas to calculate GFR and is widely used in clinical practice and research.
The MDRD equation takes into account the following variables:
- Creatinine level in the blood
- Age
- Sex
- Race (African American or not)
- Serum albumin level (a protein in the blood)
- Serum blood urea nitrogen level (a waste product in the blood)
The MDRD equation is as follows:
GFR = 175 x (serum creatinine)^-1.154 x (age)^-0.203 x (0.742 if female) x (1.212 if African American) x (serum albumin)^-0.207 x (blood urea nitrogen)^0.711
In this equation, serum creatinine is measured in milligrams per deciliter (mg/dL), age is measured in years, serum albumin is measured in grams per deciliter (g/dL), and blood urea nitrogen is measured in milligrams per deciliter (mg/dL).
The MDRD equation provides an estimated GFR (eGFR) in units of mL/min/1.73m2, which takes into account the person's body surface area. The eGFR is used to classify kidney disease into stages, ranging from stage 1 (mild kidney disease) to stage 5 (end-stage kidney disease).
It is important to note that the MDRD equation has some limitations and may not be accurate in certain populations, such as those with extremes of body size or muscle mass. In these cases, other equations or methods may be used to estimate GFR, such as the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation or cystatin C-based equations.
What is the Estimated Glomerular Filtration Rate (eGFR)?
Estimated Glomerular Filtration Rate (eGFR) is a calculated estimate of the glomerular filtration rate (GFR), which reflects how well the kidneys are filtering blood. The GFR represents the amount of blood filtered through the kidneys' glomeruli—tiny blood vessels within the nephrons—per minute. eGFR is widely used in clinical practice because it provides a non-invasive way to assess kidney function, detect kidney disease, and monitor its progression, without the need for direct and more invasive GFR measurements.
eGFR is derived using equations that factor in serum creatinine levels along with other patient-specific factors such as age, sex, body size, and ethnicity. Creatinine, a byproduct of muscle metabolism, is normally filtered by the kidneys and excreted in urine. When kidney function declines, serum creatinine levels increase, signaling reduced filtration efficiency.
The two most commonly used formulas for calculating eGFR are:
- Modification of Diet in Renal Disease (MDRD) Formula
- Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Equation
The eGFR is used to classify kidney disease into stages, ranging from stage 1 (mild kidney disease) to stage 5 (end-stage kidney disease). The eGFR is also used to monitor the progression of kidney disease over time and to help guide treatment decisions.
Diagnostic Applications of Measuring GFR
GFR measurement is used in various diagnostic settings, from assessing kidney function in healthy individuals to monitoring patients with chronic kidney disease. Its primary diagnostic applications include:
1. Diagnosis of Chronic Kidney Disease (CKD)
One of the most important uses of GFR is in diagnosing chronic kidney disease. CKD is a long-term condition characterized by a gradual loss of kidney function. A persistently low GFR (<60 mL/min/1.73 m²) for three months or more is one of the diagnostic criteria for CKD. By measuring eGFR, healthcare providers can identify individuals with impaired kidney function early, allowing for timely interventions to slow the progression of the disease.
2. Monitoring Disease Progression
For patients with established kidney disease, regular monitoring of GFR helps track the progression of the disease. A declining GFR indicates worsening kidney function, which may necessitate adjustments in treatment, such as changes in medication, dietary restrictions, or preparation for dialysis. Monitoring GFR is essential for preventing complications like fluid overload, electrolyte imbalances, and toxic build-up of waste products in the body.
3. Assessing Acute Kidney Injury (AKI)
In cases of acute kidney injury (AKI), where there is a sudden loss of kidney function, GFR can be used to assess the severity of the condition. AKI can occur due to factors such as dehydration, sepsis, medications, or trauma. By measuring serum creatinine and estimating GFR, healthcare providers can determine the extent of kidney damage and guide treatment decisions aimed at restoring kidney function.
4. Guiding Medication Dosing
Many medications are excreted by the kidneys, and impaired kidney function can lead to the accumulation of these drugs, potentially causing toxicity. GFR is used to guide medication dosing, particularly for drugs that are primarily cleared by the kidneys, such as antibiotics (e.g., vancomycin, aminoglycosides), chemotherapeutic agents, and certain blood pressure medications. For example, individuals with a low GFR may require reduced dosages or alternative medications to avoid adverse effects.
5. Pre-Transplant Evaluation
In the context of kidney transplantation, accurate GFR measurement is critical for assessing both potential donors and recipients. For kidney donors, GFR helps ensure that their remaining kidneys will have sufficient function post-donation. For recipients, GFR is used to determine eligibility for transplantation and assess the success of the transplant over time.
6. Screening for Kidney Damage in High-Risk Populations
Certain populations are at higher risk of developing kidney disease, including individuals with diabetes, hypertension, or a family history of kidney disease. In these groups, routine measurement of eGFR is used as a screening tool to detect early signs of kidney damage before symptoms appear. By identifying kidney dysfunction early, interventions such as blood pressure control, glucose management, and lifestyle changes can be implemented to slow disease progression.
Factors Influencing GFR Measurement
While GFR is a critical diagnostic tool, several factors can influence its accuracy and interpretation:
1.) Age: GFR naturally declines with age, even in healthy individuals. This means that lower GFR levels may be normal in older adults, and a decreased GFR in this population does not always indicate kidney disease.
2.) Muscle Mass: Creatinine is a byproduct of muscle metabolism, so individuals with higher muscle mass (e.g., athletes) may have higher serum creatinine levels, leading to an underestimated GFR. Conversely, individuals with low muscle mass (e.g., elderly or malnourished patients) may have artificially low serum creatinine, overestimating their GFR.
3.) Sex and Ethnicity: GFR estimation equations adjust for sex and ethnicity to account for differences in muscle mass and creatinine production. For instance, the CKD-EPI equation adjusts for African American patients due to differences in creatinine metabolism.
4.) Diet and Medications: High-protein diets, certain medications, and dehydration can also affect serum creatinine levels and, consequently, GFR estimates.
Conclusion
The glomerular filtration rate (GFR) is an important measure of kidney function and is used to diagnose and monitor a range of kidney diseases. GFR is typically measured using a blood test and a urine test, and it is calculated using a formula that takes into account the creatinine level in the blood, age, sex, and other factors.
The estimated glomerular filtration rate (eGFR) is a useful tool for monitoring kidney function and diagnosing kidney disease, as it provides an estimate of how well the kidneys are filtering waste products from the blood. It is important to monitor GFR and eGFR regularly in people with kidney disease to help guide treatment decisions and prevent complications.
