Glomerular Filtration Rate (GFR)

What is Glomerular Filtration Rate (GFR) ?

GFR is the amount of blood filtered by the glomeruli per minute (mL/min). It is the best overall indicator of kidney function. It measures how effective the kidneys filter wastes from the blood.

The glomeruli are tufts of blood capillaries in the kidneys that allow water, small dissolved substances, and wastes to pass through from the blood, while retaining blood cells and larger substances, such as proteins. From the filtered fluid, some substances are reabsorbed into the blood. The remaining fluid and wastes are excreted as urine.

As kidney function declines due to damage or disease, GFR decreases and waste products begin to accumulate in the blood.(1)

Image 1: The urinary system, including the kidneys where glomerular filtration takes place.
Picture Source: sites.google.com

Picture 2: Nephron physiology, including glomerular filtration.
Photo Source: upload.wikimedia.org

Estimated Glomerular Filtration Rate (eGFR)

The exact value of GFR is difficult to determine. Hence, GFR is estimated (eGFR) using equations based on serum creatinine or cystatin C levels.

Creatinine

Creatinine is a waste product of muscle metabolism. When released into the blood, creatinine is freely filtered in the kidneys without reabsorption. Hence, it is a good measure of GFR. When kidney function is impaired, less creatinine is excreted and its concentration increases in the blood.

The serum creatinine test can produce a good estimate of the actual GFR. However, creatinine excretion is dependent on muscle mass (hence, on sex and age), race, or amount of dietary protein.(1)

Cystatin C

The problem of serum creatinine being dependent on many factors led to the evaluation of other substances, such as cystatin C, as basis for eGFR. Cystatin C is a low-molecular weight protein produced by all cells of the body that has a nucleus.

When released into the blood, cystatin C is freely filtered in the kidneys. After glomerular filtration, cystatin C is reabsorbed and broken down at a constant rate. When kidney function is impaired, less cystatin C is excreted and its concentration increases in the blood.

Unlike creatinine, cystatin C is not significantly affected by muscle mass, race or diet. There’s evidence that cystatin C is superior to creatinine as a biomarker of kidney function. However, there is also growing evidence that cystatin C is also affected by body composition.(6, 9)

Why is eGFR calculated?

eGFR is used in the early screening of kidney damage, in the diagnosis of chronic kidney disease (CKD), and in monitoring the kidney status of people with known CKD or with risk factors for CKD, such as those with diabetes and high blood pressure.(1)

How should you prepare for the test?

For Creatinine: Do not exercise strenuously for 2 days (48 hours) prior to the test. Do not eat more than 8 oz (227 g) of meat or other protein-rich food for 24 hours prior to the test. Drink enough water during the 24 hours prior to the test.(1)

Photo 3: Protein-rich foods.
Image Source: izzihealth.com

For Cystatin C: There is no preparation needed.(9)

How is the test performed?

Blood samples are withdrawn from the vein, usually in the arm.(1)

Image 1: Blood being withdrawn from a vein in the arm.
Picture Source: laboratory-manager.advanceweb.com

How is eGFR calculated?

Modification of Diet in Renal Disease Study (MDRD) Equation

The MDRD equation has performed well in patients with chronic kidney disease. However, it underestimates the GFR in healthy patients with GFR greater than 60 mL/min.(11)

The MDRD equation is:

eGFR = 175 x (SCr)-1.154 x (age)-0.203 x 0.742 [if female] x 1.212 [if Black]

where:

eGFR = estimated glomerular filtration rate in mL/min/1.73 m2

SCr = standardized serum creatinine in mg/dL

age = years

Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Creatinine equation

This equation is the one recommended by the National Kidney Foundation for calculating eGFR in adults. It was published in 2009 as a result of efforts to create a better formula than the MDRD formula.

The CKD-EPI equation is more reliable than the MDRD equation, especially at higher GFR. However, the CKD-EPI equation is not very reliable for some populations, including elderly people, obese, and black women.(12)

The CKD-EPI creatinine equation is:

eGFR = 141 x min(SCr/κ, 1)α x max(SCr /κ, 1)-1.209 x 0.993age x 1.018 [if female] x 1.159 [if Black]

where:

eGFR = estimated glomerular filtration rate in mL/min/1.73 m2

SCr = standardized serum creatinine in mg/dL

κ = 0.7 (females) or 0.9 (males)

α = -0.329 (females) or -0.411 (males)

min = the minimum of SCr/κ or 1

max = the maximum of SCr/κ or 1

age = years

CKD-EPI Cystatin Equation

This equation may be used when a healthcare professional is not satisfied with the results of other tests, such as serum creatinine or creatinine clearance. It was published in 2012.13

The CKD-EPI cystatin equation 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 in mL/min/1.73 m2

Scys = standardized serum cystatin C in mg/L

min = the minimum of Scys/0.8 or 1

max = the maximum of Scys/0.8 or 1

age = years

Here is the simple method 🙂

Glomerular Filtration Rate (GFR) calculator

https://www.kidney.org/professionals/kdoqi/gfr_calculator

What does the rest result mean?

eGFR is usually reported as the amount of blood filtered by the glomerulus over time based on a specified body surface area (mL/min/1.73 m2). eGFR is used in the staging of CKD.(8)

The following table summarizes the CKD stage and the corresponding eGFR:

CKD STAGE	eGFR (mL/min/1.73 m2)	DESCRIPTION
1	≥90	Normal or minimal kidney damage with normal kidney function
2	60-89	Mild loss of kidney function
3	30-59	Moderate loss of kidney function
4	15-29	Severe loss of kidney function
5	<15	Kidney failure

Who is at risk for CKD?

A person is at risk for CKD if he/she:

• Has high blood pressure
• Has diabetes
• Has heart disease (heart failure, past heart attack)
• Had a stroke
• Has a family history of kidney failure
• Is obese (body mass index of greater than 30 kg/m2)
• Is a smoker
• Is at least 60 years old
• Has a history of acute kidney injury(8)

What can you do to protect your kidneys?

• Maintain a normal blood pressure (120/80 mm Hg)
• If diabetic, control blood sugar levels
• Keep a low-salt, low-fat diet
• Exercise regularly for at least 30 minutes a day on most days of the week
• Maintain a normal body weight (body mass index of 18.5 to 25 kg/m2)
• Do not smoke or if already a smoker, quit smoking(7)

References:

1. https://labtestsonline.org/tests/estimated-glomerular-filtration-rate-egfr
2. https://medlineplus.gov/ency/article/007305.htm
3. https://www.kidney.org/atoz/content/gfr
4. https://www.webmd.com/a-to-z-guides/glomerular-filtration-rate
5. https://www.niddk.nih.gov/health-information/kidney-disease/chronic-kidney-disease-ckd/tests-diagnosis
6. https://en.wikipedia.org/wiki/Renal_function#Chronic_kidney_disease_stages
7. http://www.kidneyfund.org/prevention/tests-for-kidney-health/egfr-test.html
8. https://kidney.org.au/cms_uploads/docs/estimated-glomerular-filtration-rate-egfr.pdf
9. https://labtestsonline.org/tests/cystatin-c
10. https://en.wikipedia.org/wiki/Cystatin_C#cite_note-pmid17290239-14
11. https://www.kidney.org/content/mdrd-study-equation
12. https://www.kidney.org/content/ckd-epi-creatinine-equation-2009
13. https://www.kidney.org/content/ckd-epi-cystatin-c-equation-2012