Renal Clearance: General Notes
J. Stark
ClRen depends on glomerular filtration rate(GFR), tubular reabsorption,
and tubular secretion. (In addition to urinary secretion, there is also biliary,
pulmonary, and salivary excretion. Each of these will contribute a clearance
term to the total body clearance).
When working ClRen problems, there are three important numbers to
remember:
*Renal blood flow (RBF) = 1200 ml/min
*Glomerular filtration rate (GFR) = 125 ml/min
*Urine flow = 1.5 ml/min.
(Some books may also discuss renal plasma flow and other parameters. For this
course, only the three above will be used in calculations).
1) Glomerular filtration.
Glomerular filtration is passive filtration of the blood as blood flows
through the glomeruli of the kidney. The extent to which a drug is filtered
depends on the molecular size, protein binding, ionization, polarity, and kidney
function in general. If ClRen depends only on filtration,
ClRen = GFR * fu,
where fu is the unbound fraction of drug and GFR is the glomerular filtration
rate. As given above, the normal GFR is 125 ml/min. If this number is compared
to the renal blood flow, RBF = 1200 ml/min, it becomes obvious that only 11% of
the blood is filtered: (125/1200) * (100) = 11%.
For individual patients with some renal dysfunction, the GFR is often
determined from the creatinine clearance. Creatinine is eliminated only by
glomerular filtration and has no protein binding (fu = 1). So for creatinine,
ClRen = GFR.
Determining GFR will be very important when administering a drug whose
principal means of elimination is via glomerular filtration.
2) Tubular secretion.
Tubular secretion can increase the ClRen by actively secreting the drug (as
opposed to only the passive diffusion in glomerular filtration). The rate of
secretion depends on the transporter. If the transporter is slow, the secretion
will depend on fu. Very efficient active transport (and an absence of any
reabsorption) can lead to a maximum renal clearance of
ClRen = RBF.
This is the upper limit for renal clearance.
