E-FIGURE

321-2 Models used for calculation of GFR from plasma clearance. A, One-
compartment models consider the patient as a single compartment and assume immediate
distribution of the substance used as the marker of GFR throughout the body and that the marker is
excreted from that compartment only. The plasma concentration of the chosen marker (dots) is plotted
against time. A linear slope is constructed (dashed line) and area under the slope is calculated by
dividing the zero time intercept (A) by the slope of the exponential (alpha). Clearance of the marker is
determined by dividing the dose of marker by the area under the curve. Using this model, the plasma
concentration of the marker immediately after injection exceeds that estimated by the one-
compartment model which may lead to overestimation of GFR. B, The two-compartment model
assumes that the marker is initially distributed from the vasculature (central compartment) to the
extracellular fluid volume (ECFV; peripheral component). A subsequent second elimination phase from
the body allows slow redistribution of the marker back to the plasma from the interstitial fluid as the
marker undergoes renal clearance. The log plasma concentration of the chosen marker (dots) is
plotted against time. The area under the curve is calculated from two straight lines (dashed lines)
representing an initial steep redistribution (alpha) from plasma to ECFV and the second terminal
elimination (renal clearance) phase (beta). The area under the curve is calculated using the following
equation: [A/ alpha + B/ beta], where A and B represent the zero time intercepts of the first
(distribution) and second (elimination) phase, respectively, and alpha and beta represent the slope of
their respective exponentials. Multi-compartmental models are similar to the two-compartment model
except that each component is resolved to a series of straight lines providing a theoretically more
accurate representation of the area under the curve but with the limitation that a more frequent
sampling protocol would be required. C, In a non-compartmental model the area under the curve is
calculated by adding the area of trapezoids defined by the curve. Unlike compartmental models, a non-
compartmental model is free from assumptions regarding the redistribution and elimination phases.
Errors in GFR calculation from this approach may arise because the terminal phase of elimination from
the last sample to the time of theoretical zero must be estimated and also when early ending of plasma
sampling means that a greater proportion of the curve must be estimated. D, Slope-intercept
technique for estimation of GFR. The slope-intercept technique can be used for estimation of GFR
using a limited number of samples (red dots) from only the elimination phase. Exclusion of the
distribution phase will lead to an overestimation of GFR (orange triangle) as the area under the curve
will be under-estimated. This overestimation will be proportionally larger for patients with near normal
GFR compared to patients with low GFR as the distribution phase in such patients contributes to a
greater extent of the overall area under the curve. A correction formula is applied to adjust for this.

Single
sample
methods
for
GFR
estimation
have
also
been
evaluated
both
in
dogs22,23,74
and
cats22,23,72
using
linear
regression
or
non-linear
regression
approaches
to
determine
the
best
single
sample
timing
from
multi-sample
methods.79
True
assessment
of
GFR
using
a
single
sample
method
requires
that
the
volume
of
distribution
is
known
and
that
the
sample
is
collected
at
a
time
point
when
there
is
complete
mixing
of
the
marker
through
the
volume
of
distribution.79-82
Such
an
approach
has
recently
been
evaluated
in
the
cat
and
suggests
that
optimal
sampling
time
is
180
minutes
after
iohexol
marker
administration.83
Although
this
will
be
applicable
for
the
majority
of
cats
where
GFR
measurement
is
clinically
required
(i.e.,
cats
with
near
normal
GFR),
timing
of
sampling
would
need
to
be
delayed
for
any
cat
anticipated
to
have
low
GFR.83

Plasma Exogenous Creatinine Clearance

Creatinine
is
produced
from
breakdown
of
creatinine
phosphate
within
muscle
tissue
with
minimal
impact

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