Measurement of glomerular filtration rate

1. What is the glomerular filtration rate (GFR)?

The production of urine and the removal of waste products by the kidneys begin by filtering blood across the glomerular membrane. Blood enters the glomerulus and then can exit either through the efferent arteriole or by becoming filtrate by passing through the glomerular membrane into Bowman space and the tubules of the nephron. The GFR quantifies how fast fluid is crossing the glomerular membrane.

2. What is the difference between single nephron GFR and total GFR?

Single nephron glomerular filtration rate (SNGFR), an experimentally derived value typically performed in animal models, refers to the filtration of a single nephron. SNGFR can be affected by hemodynamic alterations or structural damage. As part of the adaptation of the kidney to injury, uninjured nephrons undergo hypertrophy and hyperfiltration to compensate for the loss of functioning nephrons (compensatory hyperfiltration). Thus the total GFR that is measured or estimated) might remain relatively normal despite a decrease in functioning nephrons (see questions 5 and 8 for how to measure or estimate GFR). As such, the GFR is dependent on the number of nephrons (N) and the SNGFR, as described as follows:

A change in measured or estimated GFR could reflect either a change in nephron number or SNGFR.

3. What is the clinical significance of the GFR?

The GFR is the generally accepted, best index of kidney function. Chronic kidney disease (CKD) is defined as GFR less than 60 mL/min per 1.73 m ² as well as markers of kidney damage. In the United States the most common marker of kidney damage is urine albumin. Other markers are kidney cysts or pathologic changes in the kidney, for example. The severity of CKD is also determined by the level of GFR ( Table 3.1 ).

Decreases in GFR are associated with increasing symptoms and metabolic abnormalities. These abnormalities include anemia, acidosis, malnutrition, and bone and mineral disorders. In addition, medications that are metabolized or excreted by the kidney need to be dose adjusted (or avoided completely) in patients with decreased GFR. Even drugs that are not excreted by the kidneys can have altered pharmacodynamics and pharmacokinetics in the presence of decreased GFR. Most importantly, a GFR less than 60 mL/min per 1.73 m ² is associated with complications of CKD, including risk for kidney failure and increased total and cardiovascular disease mortality. For these reasons the GFR is the single number that best expresses kidney function.

4. What are normal values for GFR in adults?

Normal GFR varies according to age, sex, and body size; in young adults, it is approximately 120 to 130 mL/min per 1.73 m ² and declines with age.

5. How is GFR measured?

GFR is measured as the clearance of an ideal filtration marker. Clearance refers to the amount of plasma that is completely cleared of a substance over a set amount of time. For example, if a person has substance X in his blood at a concentration of 2 g X per liter and he excretes 1 g of X in the urine, he will have theoretically removed all the X from half a liter of blood. If the person took 1 day to produce enough urine to get rid of 1 g of X, then his clearance will be 0.5 L (of plasma cleared of X) per day. The equation for calculating clearance is as follows:

where Cl _x is the clearance of substance x, Ur _x is the urine concentration of X, and V is the urine flow rate.

Plasma clearance is an alternative to urinary clearance for measurement of GFR. Plasma clearance is performed by measurement timed plasma levels following a bolus intravenous injection of an exogenous filtration marker computed from the following:

where A _x is the amount of the marker administered and Px is the plasma concentration computed from the entire area under the disappearance curve.

An ideal filtration marker is one that is freely filtered at the glomerulus but not reabsorbed, secreted, or metabolized by the kidney. Clearance of an ideal filtration marker can therefore be used to measure GFR. Inulin is the ideal filtration marker. Inulin is freely filtered by the glomerulus but is neither secreted nor reabsorbed by the tubules. However, inulin is rarely used, and alterative markers include iohexol and iothalamate and are more commonly used. In addition to exogenous substances, endogenous molecules that are filtered by the glomerulus can be measured to assess GFR. In particular, creatinine clearance assessed using timed urine collections is often used to estimate GFR.

6. Why are units of GFR in milliliters/minute per 1.73 m ² ?

The clearance of substances is computed in units of milliliters/minutes. However, because kidney size (and therefore amount that can be cleared) varies by a person’s body size, to determine whether a person has normal GFR, the clearance in units of mL/min is then adjusted for normal body surface area (BSA) by multiplying by 1.73 and dividing by the individual’s BSA.