Renal physiology: GFR & clearance
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Calculating GFR
The ideal substance to calculate glomerular filtration rate (GFR) is one that has the following properties:- Freely filtered at the glomerulus
- Neither reabsorbed nor secreted as it passes through the nephron to be excreted into the urine
If a substance meets the above requirements then the amount of substance appearing in the urine minute will equal the amount filtered per minute. This may be represented by the equation below.
Cp x GFR = Cu x V
where:
- Cp = Plasma concentration of the substance
- Cu = Urine concentration of the substance
- V = Volume of urine passed per minute
It may be rearranged to give:
GFR = (Cu x V) ÷ Cp
Creatinine
Creatinine is a breakdown product of creatine phosphate from muscle and protein metabolism. It is freely filtered at the glomerulus and is not reabsorbed. There is some secretion of creatinine into the nephron but this is minimal. This makes creatinine one of the best substances for calculating GFR hence its use for this purpose in clinical practice.
A number of ideal substances do exist and may be used in some cases where plasma creatinine or GFR are very low. These markers include inulin, cystatin C, 51Cr-EDTA, 99mTc-DTPA, 125I-iothalamate and 13 iohexol. Use of these is more technically demanding, expensive and time-consuming hence why creatinine is preferred for routine estimation of GFR despite it being less accurate.
In UK clinical practice the GFR used is usually an estimated GFR (eGFR) that is calculated by inputing the serum creatinine, patient age and sex into the MDRD equation.
Clearance
Clearance is defined as the volume of plasma that would need to be completely cleared of a substance per minute in order to produce the amount found in the urine.For an ideal substance such as inulin clearance may be shown by the equation below:
clearance = (Cu x V) ÷ Cp
As can be seen this is the same equation shown above for GFR. For an ideal substance GFR = clearance. When using an ideal substance to calculate GFR it is sometimes termed using the 'clearance method'
For an ideal substance clearance = GFR
For a substance that is reabsorbed in the nephron clearance < GFR
For a substance that is secreted in the nephron clearance > GFR
For a substance that is reabsorbed in the nephron clearance < GFR
For a substance that is secreted in the nephron clearance > GFR
Some substances may be completely reabsorbed and have zero clearance. In healthy individuals this is often the case with glucose. In diabetics when high blood sugar saturates the glucose reabsorption pathway glucose starts to be cleared and enters the urine.