GLOMERULAR FILTRATION

RATE

Renal Blood Flow (RBF)

Blood enters the kidney through the
renal arteries and divides into
progressively smaller arteries
(interlobar, arcuate, and interlobular
arteries) until it enters the
glomerular capillary through the
afferent arteriole.
A portion of the plasma that enters
the glomerulus is filtered across the
glomerular membrane; this is called

Renal Blood Flow (RBF)

Under normal resting conditions, RBF is 20% of
total cardiac output.
Total blood flow is averaging 982 184 mL/min
in women and 1209 256 mL/min in men.
Renal plasma flow (RPF) is slightly less,
averaging 592 mL/min in women and 659
mL/min in men, and varies with hematocrit (RPF
= RBF [1Hct]).
RBF to the outer cortex is 2 to 3 times greater
than that to the inner cortex, which in turn is two
to four times greater than that to the medulla.

Determinants of Glomerular
Filtration
Through the passive ultrafiltration of
plasma across the glomerular
membrane, the kidney is able to
regulate total body salt and water
content, electrolyte composition, and
eliminate waste products of protein
metabolism.

Determinants of Glomerular
Filtration
The glomerular filtration rate (GFR) is thus
determined by both hydraulic and oncotic
pressure differences between the
glomerular capillary and the Bowman
space, as well as by the permeability of the
glomerular membrane:
GFR = LpS (hydrostatic pressure oncotic
pressure)

- Lp = glomerular permeability
- S = glomerular surface area

Determinants of Glomerular
Filtration
The rate at which filtration occurs
within an individual nephron is
termed the single nephron GFR
(SN-GFR).
A more relevant measurement is that
of total GFR, which is the sum of all
SN-GFR and is expressed in milliliters
per minute.
GFR is thus a reflection of overall
renal function.

Determinants of Glomerular
Filtration
Transglomerular (hydraulic) pressure (TGP)
Glomerular capillary is interposed between two
arterioles (the afferent and efferent arterioles)
and thus can regulate intraglomerular capillary
pressure (IGP) independent of systemic
pressures through changes in afferent and
efferent arteriolar tone.
Under normal circumstances, the pressure within
the Bowman space is essentially zero, and only
in conditions of urinary obstruction does the
pressure increase to clinically significant levels.

Determinants of Glomerular
Filtration
Renal plasma flow
Increases in RPF lead to increases in
GFR.

Determinants of Glomerular
Filtration
Glomerular permeability
Increase in permeability does not lead to
an increase in GFR, because the
glomerulus is already at maximal
permeability for water and other relevant
solutes. It may, however, lead to increased
filtration of larger molecules not normally
filtered, such as albumin.
Reductions in permeability, or in glomerular
surface area, can lead to reductions in GFR.

Determinants of Glomerular
Filtration
Oncotic pressure
Under normal circumstances, plasma
proteins are not filtered across the
glomerular membrane and so oncotic
pressure within the Bowman space is
essentially zero.

Regulation of GFR
Autoregulation
Increases in mean arterial pressure (MAP), afferent
arteriolar tone increases to minimize increases in IGP.
Reductions in MAP, afferent arteriolar tone decreases
to allow increased flow into the glomerulus to
maintain IGP, thus maintaining GFR.
Autoregulation of IGP is effective to a MAP of about
70 mm Hg, and below a MAP of 40 mm Hg, filtration
ceases.
It is likely mediated through myogenic stretch
receptors in the afferent arteriole wall, possibly
mediated by adenosine triphosphate (ATP.

Regulation of GFR
Tubuloglomerular feedback (TGF)
If SN-GFR increases, delivery of sodium cations (Na+) and
chloride anions (Cl) to the distal tubule also increases.
This increased Cl delivery triggers a response by the
macula densa, which ultimately leads to an increase in
afferent arteriolar tone and subsequent decrease in RPF,
thus returning SN-GFR (and tubular flow) back to baseline.
It seems that angiotensin II plays a permissive role in TGF.
Both adenosine and thromboxane can cause afferent
arteriolar vasoconstriction and have been implicated in
TGF.
Nitric oxide is also believed to be important, particularly in
minimizing TGF in the setting of increased NaCl intake.

Regulation of GFR
Both norepinephrine and angiotensin
II play an important role in
maintaining GFR through arteriolar
vasoconstriction.
Inhibition of PG synthesis can lead to
severe vasoconstriction and acute
reduction in GFR.

Renal Clearance
The best estimate of GFR can be obtained by
measuring the rate of clearance of a given
substance from the plasma.
However, in order to be accurate, the substance to
be measured must meet certain criteria. It must:
Be able to achieve a stable plasma concentration,
Be freely filtered across the glomerulus,
Not be secreted, reabsorbed, synthesized, or
otherwise metabolized by the renal tubules, and
Not be impacted by any other means of removal
from the plasma.

Renal Clearance
GFR = U[X] urine volume/P[X]
This is called the clearance of a
substance and reflects the amount of
plasma that is completely cleared of
the substance per unit time.

Renal Clearance
There are a number of substances that
have been used clinically to estimate
GFR :
1. Inulin
2. Radiolabelled compoundssuch as
iothalamate or
diethylenetriaminepentaacetic acid
(DTPA).
3. Creatinine

Plasma Markers
An even simpler method to estimate
GFR is with the use of plasma levels of
substances that can be used as
surrogate markers of GFR.
Three such substances have been used:
1. Plasma creatinine (PCr)
2. Plasma urea
3. Plasma cystatin C

Mathematical Correction
The two most widely used are the
Cockcroft-Gault and modification of
diet in renal disease (MDRD)
formulas.

Cockcroft-Gault
Originally developed from data collected from
individuals with normal renal function; it is a
simple formula to estimate CrCl (not GFR) that
corrects for age, sex, and body mass.
The formula is :

It has the advantage of being very simple, but is

not as accurate as other methods when renal
function is impaired.

MDRD Formulas
A series of formulas derived from data
collected in patients with severe renal
impairment.
They are more complex but more accurate
than the Cockcroft-Gault.
The simplest estimate of GFR is the fourvariable equation :

Key Points
GFR reflects total renal function.
GFR can be approximated by
creatinine clearance.
Formulas based on patients age,
weight, and serum creatinine can
best estimate GFR.