Clearance (medicine)

In medicine, the clearance is a measurement of the renal excretion ability. Although

clearance may also involve other organs than the kidney, it is almost synonymous with
renal clearance or renal plasma clearance. Each substance has a specific clearance
that depends on its filtration characteristics. Clearance is a function of glomerular
filtration, secretion from the peritubular capillaries to the nephron, and reabsorption from
the nephron back to the peritubular capillaries.

Definition
When referring to the function of the kidney, clearance is considered to be the amount of liquid
filtered out of the blood that gets processed by the kidneys or the amount of blood cleaned per
time because it has the units of a volumetric flow rate [ volume / time ]. However, it does not
refer to a real value; "[t]he kidney does not completely remove a substance from the total renal
plasma flow."[1] From a mass transfer perspective and physiologically, volumetric blood flow (to
the dialysis machine and/or kidney) is only one of several factors that determine blood
concentration and removal of a substance from the body. Other factors include the mass
transfer coefficient, dialysate flow and dialysate recirculation flow for hemodialysis, and the
glomerular filtration rate and the tubular reabsorption rate, for the kidney. A physiologic
interpretation of clearance (at steady-state) is that clearance is a ratio of the mass generation
and blood (or plasma) concentration.

Its definition follows from the differential equation that describes exponential decay and
is used to model kidney function and hemodialysis machine function:

Where:

 is the mass generation rate of the substance - assumed to be a constant, i.e. not a
function of time (equal to zero for foreign substances/drugs) [mmol/min] or [mol/s]
 t is dialysis time or time since injection of the substance/drug [min] or [s]
 V is the volume of distribution or total body water [L] or [m³]
 K is the clearance [mL/min] or [m³/s]
 C is the concentration [mmol/L] or [mol/m³] (in the USA often [mg/mL])

In steady-state, it is defined as the mass generation rate of a substance (which equals

the mass removal rate) divided by its concentration in the blood.
Effect of plasma protein binding

For substances that exhibit substantial plasma protein binding, clearance is generally
defined as the total concentration (free + protein-bound) and not the free concentration.

Most plasma substances have primarily their free concentrations regulated, which thus
remains the same, so extensive protein binding increases total plasma concentration
(free + protein-bound). This gives a decreased clearance than what would have been
the case with no protein binding. [3] However, the mass removal rate is the same[3],
because it depends only on concentration of free substance, and is independent on
plasma protein binding, even with the fact that plasma proteins increase in
concentration in the distal renal glomerulus as plasma is filtered into Bowman's capsule,
because the relative increases in concentrations of substance-protein and non-occupied
protein are equal and therefore give no net binding or dissociation of substances from
plasma proteins, thus giving a constant plasma concentration of free substance
throughout the glomerulus, which also would have been the case without any plasma
protein binding.

In other sites than the kidneys, however, where clearance is made by membrane
transport proteins rather than filtration, extensive plasma protein binding may increase
clearance by keeping concentration of free substance fairly constant throughout the
capillary bed, inhibiting a decrease in clearance caused by decreased concentration of
free substance through the capillary.

Measurement of renal clearance

Renal clearance can be measured with a timed collection of urine and an analysis of its
composition with the aid of the following equation (which follows directly from the
derivation of (10b)):

Where:

 K is the clearance [mL/min]

 CU is the urine concentration [mmol/L] (in the USA often [mg/mL])
 Q is the urine flow (volume/time) [mL/min] (often [mL/24 hours])
 CB is the plasma concentration [mmol/L] (in the USA often [mg/mL])

When the substance "C" is creatinine, an endogenous chemical that is excreted only by
filtration, the calculated clearance is equivalent to the glomerular filtration rate. Inulin
clearance is also used to estimate glomerular filtration rate.