Renal Clearance Concepts
Dr. shafali singh
Learning Objectives:
• To define renal clearance and calculate renal clearance of
different substances. Calculate GFR values using inulin
clearance.
• Calculate renal plasma flow and RBF using PAH clearance
and hematocrit.
• Characterize tubular transport using solute clearance.
• Define the basis for the clinical use of plasma creatinine
and urea levels to assess renal function.
• List different markers used for measuring GFR, RPF and
RBF
• Understand fractional clearance of a substance (Na) and
its importance
• Understand osmolar clearance and free water clearance
ASSESSMENT OF RENAL FUNCTION
• The principle of renal clearance emphasizes the
excretory function of the kidneys;
• it considers only the rate at which a substance is
excreted into urine and not its rate of return to the
systemic circulation in the renal vein.
• Therefore, in terms of mass balance the urinary
excretion rate of substance x (Ux × V.) is
proportional to the plasma concentration of
substance x,
To equate the urinary excretion rate of substance x to its renal
arterial plasma concentration, it is necessary to determine the
rate at which it is removed from plasma ;by the kidneys. This
removal rate is the clearance (Cx).
• Thus, the 2 factors which determine clearance
are the plasma concentration of the substance
and its excretion rate.
• Urine flow (V) is a volume per unit time, and the units of V will
become the units of clearance.
• Clearance is a volume of plasma cleared of a substance per
unit time, mL/min or L/day.
Clearance
• Clearance refers to a theoretical volume of plasma
from which a substance is removed over a period of
time.
•
•
•
•
•
•
example: If the concentration of substance x is 4 molecules
per liter and the excretion of x is 4 molecules per minute,
the volume of plasma cleared of x is 1 L per minute.
If the excretion of x decreases to 2 molecules per minute,
the volume cleared of x is only 0.5 L per minute.
If the concentration of x decreases to 2 molecules per liter of
plasma and the excretion is maintained at 2 molecules per
minute,
the cleared volume is back to 1 L per minute.
• Renal plasma clearance is the volume of
blood that is “cleaned” or cleared of a
substance per unit of time, usually
• expressed in units of milliliters per minute.
• High renal plasma clearance indicates efficient
excretion of a substance in the urine; low
clearance indicates inefficient excretion
Clearance Example
• Substance Z has a urine concentration of 100
mg/ml
• Urine flow rate is 1 ml/min
• Plasma concentration is 1 mg/ml
Calculate the Clearance ?
Clearance Example
• Calculate the Clearance
CZ = Uz • V
Pz
CZ = (100mg/ml) • (1 ml/min)
1 mg/ml
CZ = 100 ml/min
The clearance of a solute depends on the three
basic processes of a nephron:
1. glomerular filtration,
2. tubular reabsorption,
3. and tubular secretion.
Consider a substance that is filtered but neither
reabsorbed nor secreted. Its clearance equals
the glomerular filtration rate because all the
molecules that pass the filtration membrane
appear in the urine.
• This is very nearly the situation for creatinine;
it easily passes the filter, it is not reabsorbed,
and it is secreted only to a very small extent
• Measuring the creatinine clearance, which
normally is 120–140 mL/min, is the easiest
way to assess glomerular filtration rate.
.
Creatinine
• Creatinine is a byproduct of skeletal muscle
creatine metabolism and is released from
skeletal muscle at a constant rate proportional
to muscle mass.
• Creatinine is freely filtered and not reabsorbed
by the kidney, although a very small amount is
secreted into the proximal tubule.
• Creatinine production = creatinine excretion =
filtered load of creatinine = Pcr × GFR
excreted load of creatinine= Ucr × V
CLINICAL ESTIMATION OF GFR
• The GFR is equal to the sum of the filtration
rates of all functioning nephrons. Thus, it is an
index of kidney function.
• A fall in GFR means the disease is progressing,
whereas an increase in GFR suggests a
recovery.
• Estimations of GFR rely on the concept of
clearance
• Thus, if creatinine production remains
constant, a decrease in GFR would be
reflected by an increase in plasma creatinine
concentration, and an increase in GFR would
be reflected by a decrease in plasma
creatinine.
• Plasma creatinine, however, is not a very
sensitive measure of reduced GFR. It will only
reveal large changes in GFR.
•
•
•
•
•
Any substance that meets the following
criteria can serve as an appropriate marker
for the measurement of GFR.
The substance must
Be freely filtered across the glomerulus into
Bowman's space
Not be reabsorbed or secreted by the nephron
Not be metabolized or produced by the kidney
Not alter the GFR
Stable plasma concentration that is easily
measured
Ideal substances would include
• inulin
Alternatives include radioactive
iothalamate, iohexol, diethylene triamine
pentaacetic acid (DPTA), and the related
• sucrose
ethylene diamine tetraa-cetic acid
(EDTA).
• mannitol
Even though the clearance of inulin is
considered the gold standard for the
measurement of GFR, it is not used clinically.
Instead clinical estimates of GFR rely on
creatinine
Q
• A 35-year-old woman is being evaluated for
renal surgery. Her plasma creatinine
concentration (PCr) is 0.8 mg/dL. A 24-hour
urine collection has a creatinine concentration
(UCr) of 90 mg/dL and a total volume (V) of
1,425 mL. What is her glomerular filtration
rate (GFR)?
Para-aminohippuric acid
(PAH)
The clearance of the organic anion para-amino
hippuric acid (PAH) is also of clinical
importance.
After PAH is administered intravenously, it is
filtered and secreted in a single pass through
the kidneys.
Thus, the clearance of PAH is used to measure
renal plasma flow, the amount of plasma that
passes through the kidneys in one minute.
120 mL/min by
filtration and 480
mL/min by
secretion. As such
there would be no
PAH in the renal
venous blood
Effective
RPF = renal plasma flow (mL/min or mL/24hr)
CPAH = clearance of PAH (mL/min or mL/24 hr)
[U]PAH = urine concentration of PAH (mg/mL)
V = urine flow rate (mL/min or mL/24 hr)
[P]PAH = plasma concentration of PAH (mg/mL
Measurement of renal plasma flow (RPF)—
clearance of para-aminohippuric acid (PAH)
Clearance of PAH measures effective RPF and
underestimates true RPF by 10%.
• PAH clearance at low plasma concentrations is
referred to as effective renal plasma flow (ERPF)
because some plasma perfuses the renal capsule.
This flow (about 10%) is not cleared of PAH.
• Thus, PAH clearance is only 90% of the true renal
plasma flow.
True RPF
Q
• A healthy 22-year-old man volunteers for a
research study evaluating the effects of a new
drug on renal blood flow (RBF).
• The protocol required a urinary catheter to
measure kidney output while infusing paraaminohippuric acid (PAH) intrave-nously. PAH
concentration (PPAH) stabi-lized at 0.025 mg/mL.
Urine flow rate (V) was then measured at 1.2
mL/min, and urine PAH concentration (UPAH) was
18 mg/mL.
• Hematocrit (Hct) was 48%. What was the
subject’s RBF?
Clearance curves
General pattern of clearance
• Glucose: The normal clearance of glucose is
zero.
• Sodium: Always appears in the urine, thus
sodium always has a positive clearance
• Urea: Is freely filtered but partially
reabsorbed
• Inulin: is freely filtered and there is no
transport. its clearance always equals GFR
regardless of its plasma concentration
• Creatinine: Since with creatinine everything
filtered is excreted plus a small amount
secreted, it has a clearance slightly greater
than GFR.
• PAH: The greatest clearance via the kidney is
renal plasma flow this is the clearance of PAH
at low plasma concentrations,.
Fractional Excretion (FExx)
• Another way of using Clearance to assess how
kidney handles a substance is to compare
Clearance of substance to clearance of
creatinine or inulin.
FEx = [(Uz)(Volurine)]/Pz
[(Uin)(Volurine)]/Pin
=
(Uz)/Pz
(Uin)/P in
Clearance ratio
• If C z/C in=1 the substance is filtered, but not
reabsorbed nor secreted.
• If C z/C in<1 the substance is not filtered, or
filtered and subsequently reabsorbed
• If C z/C in >1 the substance is filtered and
secreted.
Q
1. What does aldosterone do to clearance of
Na?
2. What does PTH do to clearance of Ca and
PO4?
3. Clearance of urea during dehydration and
diuresis?
question
Q Which of the following substance is cleared
the most by the kidneys?
• Inulin
• PAH
• Creatinine
• Urea
Q
• What is the term used to describe the amount
of pure water that would be added or
removed from urine per unit time in order to
make it have the same osmolarity as plasma?
Free Water Clearance
• Free water clearance is the best measure of the
balance between solute and water excretion.
• Its use is to determine whether the kidneys are
responding appropriately to maintain normal
plasma osmolarity.
• Free water clearance is how much solute-free
water is being excreted; it is as if urine consisted
of plasma (with solutes) plus or minus pure water
Q What kidney ability is free water clearance
actually a measure of?
FWC is measure of the ability of the kidney to
excrete water
• Q What kind of urine generate a value of zero
for free water clearance?
• iso osmotic urine
• Positive-free water clearance tends to cause
increased plasma osmolarity;
• negative free water clearance causes reduced
plasma osmolarity.
Q. What kind of urine generate a negative value
for free water clearance?
Hyperosmotic urine
Q. What kind of urine generate a positive value
for free water clearance?
Hypo osmotic urine
• If urine osmolarity was 300 mOsm/L (isotonic
urine), free water clearance would be zero.
• If plasma osmolarity is too low, urine osmolarity
should be lower still(positive free water
clearance) in order to compensate.
• Positive-free water clearance tends to cause
increased plasma osmolarity;
• negative free water clearance causes reduced
plasma osmolarity.
• CH2O (+) = hypotonic urine is formed (osmolarity
<300 mOsm/L)
• CH2O (–) = hypertonic urine is formed (osmolarity
>300 mOsm/L)
• FWC
= 1 – urine osmolarity × V
plasma osmolarity
Where V is volume of urine per unit time
Q
• V = 3.0 mL/min
• Uosm = 800 mOsm/L
• Posm = 400 mOsm/L
What is the free water clearance?
Free water reabsorption( FWR)
• Opposite of FWC
= urine osmolarity
–1 × V
plasma osmolarity
• During the production of hyperosmotic urine
FWR will be +ve,--ve or Zero?