Glomerular Filteration Rate

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GFR?

Back 1

The glomerular filtration rate (GFR) is the rate at which
fluid passes into nephrons after filtration and is a
measure of renal function.

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rel to body size?

Back 2

It is proportionate to body size

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ref range

Back 3

and the reference range is usually expressed after correction for body surface area as 120 ± 25 mL/min/1.73m2

Hint 3

120 ± 25 mL/min/1.73m2

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Direct meas

Back 4

The GFR may be measured directly by
injecting and measuring the clearance of compounds
such as inulin or radiolabelled ethylenediamine­
tetracetic acid, which are completely filtered at the
glomerulus and are not secreted or reabsorbed by the
renal tubules

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when dir?

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However, this is not performed
routinely and is usually reserved for special circum­
stances, such as the assessment of renal function in
potential live kidney donors

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Clinical prc

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Instead, GFR is usually
indirectly assessed in clinical practice by measuring
serum levels of endogenously produced compounds that are excreted by the kidney

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widely used comp

Back 7

The most widely used
is serum creatinine, which is produced by muscle at a
constant rate, is almost completely filtered at the glomer­
ulus, and is not reabsorbed.

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Signif

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Although creatinine is
secreted to a small degree by the proximal tubule, this
is only usually significant in terms of GFR estimation in
severe renal impairment, where it accounts for a larger
proportion of the creatinine excreted

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creatinine and GFR

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Accordingly, pro­vided muscle mass remains constant, changes in serum
creatinine concentrations closely reflect changes in GFR,
although the reference range for creatinine is wide due
to the fact that muscle mass varies widely between dif­
ferent individuals

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measurement

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Several methods have been
developed with which to estimate GFR from serum creatinine measurements

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widely used eq

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but the most
widely used is the MDRD equation, which is now the
accepted standard for assessing estimated GFR (eGFR)

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Signi of eGFR

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Although the eGFR has several limitations (Box 17.2), its
routine reporting by laboratories has increased recogni­tion of moderate kidney damage and encouraged early
deployment of protective therapies

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Assessment

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A potentially more accurate assessment of GFR can
be obtained by collection of a 24­hour urine sample and
relating serum creatinine levels to urinary creatinine
excretion

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17.1 How to estimate glomerular filtration
rate (GFR

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01. Measuring GFR

02. Estimating with equations

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Measuring GFR

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• Direct measurement
• Creatinine clearance (CrCl

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Direct Meas

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using labelled EDTA or inulin

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Creatinine clearance (CrCl

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Minor tubular secretion of creatinine causes CrCl to
exaggerate GFR when renal function is poor, and can be
affected by drugs )
Needs 24-hr urine collection (inconvenient and often
unreliable)

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drugs aff crCl

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(e.g. trimethoprim, cimetidine

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CrCl mL/min =

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mg/dl to umol/L

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To convert
creatinine in mg/dL to µmol/L, multiply by 88.4.

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02. Estimating with Equations

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• Cockcroft and Gault equation

• The Modification of Diet in Renal Disease (MDRD) study
equation

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• Cockcroft and Gault equation

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Reasonably accurate at normal to moderately impaired
renal function
Estimates CrCl, not GFR
Requires patient weight

Hint 22

Advantages

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Equation

Back 23

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• The Modification of Diet in Renal Disease (MDRD) study
equation (see www.renal.org/eGFR

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Performs better than Cockcroft and Gault at low GFR
Requires knowledge of age and sex only
Can be reported automatically by laboratories

Hint 24

Benefits

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Equation

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Hint 25

*A correction factor, either a value recommended by the laboratory/assay
manufacturer or a default value of 186; see www.renal.org/ckd.

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Limitations of eq

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• No equations perform well in unusual circumstances, such as
extremes of body (and muscle) mass or in acutely unwell
patients (see Box 17.2

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Limitations

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01. Extremes of wt

02. Confidence Intervals

03. Changes Signicance

04. Value in AKI

05. Racial Groups

06. Special Population

07. Elderly

08. Normal func underestimation

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01. Extremes of wt

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• It is only an estimate, least reliable at extremes of body
composition (malnourished, amputees) and in hospital
inpatients (as it was derived from outpatients)

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02. Confidence Intervals

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• Confidence intervals are wide (90% of patients will have
eGFR within 30% of their measured GFR, and 98%
within 50%)

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03. Changes Signicance

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• Values are consistent in individuals, so changes mean more
than absolute values

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04. Value in AKI

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• Creatinine level must be stable over days; eGFR is not valid
in assessing acute kidney injury

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08. Normal func underestimation

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• It tends to underestimate normal or near-normal function, so
slightly low values should not be over-interpreted. Many
laboratories report only up to > 60 mL/min/1.73 m
2
for this
reason

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07. Elderly

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• In the elderly, who constitute the majority of those with low
eGFR, there is controversy about categorising people as
having chronic kidney disease (CKD; Box 17.3) on the basis
of eGFR alone, particularly at stage 3A, since there is little
evidence of adverse outcomes when eGFR is > 50 unless
there is also proteinuria

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05. Racial Groups

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• The equation was originally validated in US patients and
eGFR for any given creatinine was 21% higher in blacks.
Performance in other racial groups is under investigation

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06. Special Population

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• eGFR is not valid in under-18s or during pregnancy

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Serum cr rel to GFR

Back 36

Hint 36

Fig. 17.2 Serum creatinine and the glomerular filtration rate
(GFR).The inverse reciprocal relationship between GFR and serum
creatinine is shown for a group of patients with renal disease. The red
band indicates the range of values obtained. Note that some individuals
have a GFR as low as 30–40 mL/min without serum creatinine rising out
of the reference range