28. Glomerular Filtration Rate Flashcards
What do you understand by the term glomerular filtration rate (GFR)?
Glomerular filtration rate is a unit of
measure of kidney excretory function,
and can be defined as the
volume of plasma cleared of an
ideal substance per unit time
(or the volume of plasma filtered
at the glomerulus per unit time).
It is usually expressed as mL/min,
and is approximately
125 mL/min or
180 L/day.
Values in women are ±10% lower than those in men.
The classification of chronic kidney disease is largely based on calculated or estimated GFR.
Define filtration fraction (FF).
This is the ratio of GFR to RPF (∼0.16–0.2).
Renal plasma flow (RPF) represents the
total amount of potentially filterable
fluid entering the kidneys (600–700 mL/min).
Of this, 125 mL/min forms the
GFR (20%) while the remainder
continues into the efferent arterioles.
How can GFR be measured?
GFR can either be calculated
(using the plasma clearance of a suitable
substance, by applying the Fick principle)
or estimated using prediction formulae
(based on factors such as the patient’s age, sex and serum creatinine level
How can GFR be measured?
Estimated (eGFR)
The most commonly used are the Cockcroft and Gault (C&G) equation and formulas based on the modification of diet in renal disease study (MDRD).
• C&G: inaccurate in
overweight individuals
and in fluid overload.
• MDRD: most validated formula for
eGFR and used in most laboratories.
It does not require weight or height variables because results are reported normalised to 1.73 m2 body surface area.
Calculated applying the Fick principle
and using the formula for clearance
of a substance (inulin/creatinine):
Clearance (GFR) =
Urine flow Urine concentration × \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_
Plasma concentration
How and why is inulin used to assess renal function?
Inulin,
an exogenous polysaccharide
with a molecular weight of 5200 Daltons,
meets all the criteria of an ideal substance as follows:
• Freely filtered through
the glomeruli
(not bound to protein)
- Not reabsorbed nor secreted
- Not metabolised
- Not stored in the kidney
- No effect on the filtration rate
- Not toxic
- Easy to measure in plasma and urine.
The use of inulin is limited because of its expense and impracticalities.
Its administration requires a bolus followed by an infusion, and collection of
blood and urine samples over several hours. Nowadays it is used mostly for
research, where very accurate assessments of GFR are required.
Discuss alternatives to inulin along with their limitations.
Creatinine
Creatinine
> Urine [creat] may be elevated
due to tubular secretion,
but this is often cancelled out
by plasma [creat],
which is raised due to
non-specific chromogens.
> In practice, creatinine clearance
is no longer used to measure GFR,
as a 24-hour urine collection
is required,
which is impractical for patients and
leads to inaccuracies in measurement.
> It is affected by muscle mass,
diet and
tubular secretion.
A trend in values,
rather than a single measurement is
more important when
assessing renal function.
> It also remains within the normal range until a significant reduction in renal function occurs particularly in the elderly who have a reduced muscle mass.
> Drugs such as ACE inhibitors (ACEI) or
angiotensin II receptor
antagonists (ARB) may
increase serum creatinine by up to 30%.
Urea
> Less reliable than creatinine because
40–50% of filtered urea
may be reabsorbed by the tubules.
> Non-renal factors may affect serum levels
(urea is raised with a high protein diet, tissue breakdown, major gastrointestinal haemorrhage and corticosteroid therapy;
lowered with a low protein diet
and liver disease).
Cystatin C
> Endogenous substance,
freely filtered but limited due
to wide variation in
serum levels.
> At present, it has no clinical role in GFR measurement.
What factors affect GFR?
These are the same as those
governing filtration across any capillary bed:
> Permeability of capillaries
> Size of capillary bed (surface area)
> Hydrostatic and osmotic pressure
gradients across the capillary wall
(Starling’s forces).
Capillary permeability
> Glomerular capillary wall is highly
permeable due to its fenestrations.
> Neutral substances of < 4 nm diameter
are freely filtered,
but > 8 nm,
their filtration approaches zero.
> Between 4 and 8 nm,
their filtration is inversely
proportional to diameter
(Graham’s law).
> The basement membrane’s negative
charge repels negatively charged
ions, whose filtration is
greatly reduced, e.g. albumin.
> The filtration of positively charged ions
is slightly greater than that of neutral substances.
Size of capillary bed (surface area)
> Mesangial cells,
located between the capillary endothelium
and the basement membrane,
have a contractile function,
reducing the surface
area available for filtration.
> Many vasoactive substances
affect the mesangial cells,
e.g. angiotensin 2 contracts while PGE2 relaxes.
Starling’s forces
> The net filtration rate is a
function of the forces favouring
filtration and those opposing it,
and can be described by the following equation:
GFR = Kƒ [(PGC − PB) − (ΠGC − ΠB)]
here:
Kƒ = glomerular filtration coefficient
(permeability × capillary bed surface area)
PGC = hydrostatic pressure in glomerular capillary
PB = hydrostatic pressure in Bowman’s capsule
ΠGC = colloid osmotic pressure in glomerular capillary
ΠB = colloid osmotic pressure in Bowman’s capsule
> PGC pressure - how does it compare to other capillary beds
> PGC is higher (45 mm Hg)
than in other capillary beds (32 mm Hg)
because:
1 • Afferent arterioles are short and straight
2 • Efferent arterioles have a relatively high resistance
> PGC favours filtration and is opposed by:
> PGC favours filtration and is opposed by:
- Hydrostatic pressure in Bowman’s capsule
- Osmotic pressure gradient across the glomerular capillaries (ΠGC − ΠB)
ΠB is usually negligble
The equation can therefore be expressed as:
ΠB is usually negligible and the osmotic pressure gradient is generally equal to the pressure exerted by the plasma proteins within the glomerular capillaries (ΠGC).
The equation can therefore be expressed as:
GFR = Kƒ [PGC − PB − ΠGC]
• PGC remains constant from afferent to efferent
end of the glomerular capillary (45 mm Hg),
as does the PB (10 mm Hg).
• ΠGC rises from 20 mm Hg
at the afferent end to 35 mm Hg
at the efferent end
because plasma proteins become
progressively more concentrated as
filtration occurs along the length of the capillaries.
• Just proximal to the efferent arteriole,
the net ultrafiltration pressure is
reduced to zero and filtration ceases.
Table 28.1 Starling pressures (mmHg) at the afferent and efferent arteriole
Table 28.1 Starling pressures (mmHg) at the afferent and efferent arteriole Afferent end Efferent end PGC 45 45 PB 10 10 ΠGC 20 35 Net 15 0
