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---
title: Kidneys
author: Vesa Oikonen
updated_at: 2021-03-30
updated_at: 2021-04-06
created_at: 2017-02-23
tags:
- Kidney
......@@ -248,10 +248,11 @@ GFR &lt;60 mL/min/1.73 m<sup>2</sup> for at least three months has been used a c
<a href="./dis_ckd.html">chronic kidney disease</a>. After tubular reabsorption, the
<a href="./urine.html">urine</a> flow rate is only about 1 mL/min.</p>
<p>GFR is considered the best overall index of <em>kidney function</em>, including also tubular
function, but its measurement is not simple.
It can be measured (mGFR) indirectly as the clearance of administered (bolus infusion)
filtration markers, or estimated (eGFR) from serum levels of endogenous filtration markers.
<p>GFR is considered the best overall index of <em>kidney function</em> (renal function), which
also includes <a href="#tubular">tubular function</a>.
Measurement of GFR is not simple: it can be measured (mGFR) indirectly as
the <a href="#renal_clearance">clearance</a> of administered (bolus infusion) filtration markers, or
estimated (eGFR) from serum levels of endogenous filtration markers.
Endogenous filtration markers are substances that body produces at a relatively constant rate,
such as creatinine, urea, and cystatin C.
Exogenous filtration markers are substances with relatively low molecular weight that are not
......@@ -259,8 +260,6 @@ protein bound, not reabsorbed, secreted, or metabolized by the tubules, and main
the circulation by glomerular filtration; for instance inulin, [<sup>51</sup>Cr]EDTA, and
[<sup>99m</sup>Tc]DTPA have been used for this purpose.
<a href="./analysis_68ga-dota.html">[<sup>68</sup>Ga]DOTA</a> could be used to measure GFR with PET.
If elimination is only via glomerular filtration, the plasma and urinary clearances are equal,
obviating the need for error prone urinary collection.
[<sup>68</sup>Ga]EDTA and [<sup>55</sup>Co]EDTA have also been used to assess GFR
(Yamashita et al., <a href="https://doi.org/10.1620/tjem.155.207">1988</a> and
<a href="https://doi.org/10.3769/radioisotopes.38.9_373">1989</a>;
......@@ -294,6 +293,58 @@ nephron from Bowman's capsule to the collecting ducts, and renal cells are expos
exposed to stretch and shear stress
(<a href="https://doi.org/10.1038/ki.2015.65">Peti-Peterdi et al., 2015</a>).</p>
<p>Renal function is proportional to the size of kidneys, which is proportional to
body surface area (BSA). In inter-individual comparisons the GFR must be adjusted to BSA
(<a href="https://doi.org/10.1111/bcp.12198">Sandilands et al., 2013</a>).</p>
<h3><a name="renal_clearance">Renal clearance</a></h3>
<p>Renal plasma clearance (<em>CL<sub>R</sub></em> ) of a drug is the virtual volume of plasma from
which drug is completely removed per unit time by the kidneys, independent of other pharmacokinetic
processes (<a href="https://doi.org/10.1111/j.1365-2125.1981.tb01304.x">Tucker, 1981</a>).
It can be defined as the product of renal plasma flow (<em>Q<sub>R</sub></em> ) and the renal
extraction ratio (<em>E<sub>R</sub></em> ):</p>
<a name="eq_cl_r_1"></a>
<div class="eqs">
<script type="math/tex; mode=display">
\begin{equation}
CL_R = Q_R \times E_R
\end{equation}
</script>
<script type="math/tex; mode=display">
\begin{equation}
E_R = \small{1 - \frac{\text{Concentration of drug in renal venous plasma}}{\text{Concentration of drug in renal arterial plasma}}}
\end{equation}
</script>
</div>
<p>If drug is eliminated from system only via glomerular filtration, the renal plasma clearance and
<a href="./urine.html#urinary_clearance">urinary clearance</a> are equal. Both can then be assessed
via plasma sampling or urinary collection. Urinary collection is prone to errors, providing less
precise results as calculation of <a href="./input_pk.html#total_clearance">clearance</a> from plasma
measurements. Urinary clearance can be higher than GFR if the drug undergoes tubular secretion
(<a href="https://doi.org/10.1259/bjr.71.851.10434905">Peters, 1998</a>).</p>
<p>If the fraction of unbound drug in plasma (<em>f<sub>p</sub></em> ) is known, <em>GFR</em> and
<em>CL<sub>R</sub></em> are related by equation</p>
<a name="eq_gfr"></a>
<div class="eqs">
<script type="math/tex; mode=display">
\begin{equation}
CL_R = f_p \times {GFR}
\end{equation}
</script>
</div>
<p>While it is generally considered that only free drug in plasma can be excreted to urine,
<a href="./plasma_protein_binding.html">plasma protein bound</a> drug and/or drug in erythrocytes
may also be available for tubular excretion, if equilibration of free drug in plasma between these
components is rapid.</p>
<h2><a name="tubular">Tubular function</a></h2>
......
---
title: Urine in PET studies
author: Vesa Oikonen, Tuula Tolvanen
updated_at: 2021-03-26
updated_at: 2021-04-06
created_at: 2018-10-05
tags:
- Urinary bladder
......@@ -114,52 +114,61 @@ deriving <a href="./input_idif.html">input function</a> in small animal FDG PET
(<a href="https://doi.org/10.1007/s11307-013-0610-6">Wong et al., 2013</a>).</p>
<h3><a name="renal_clearance">Renal clearance</a></h3>
<h3><a name="urinary_clearance">Urinary clearance</a></h3>
<p>Renal plasma clearance (<em>CL<sub>R</sub></em> ) of a drug is the virtual volume of plasma from
which drug is completely removed per unit time by the kidneys, independent of other pharmacokinetic
processes (<a href="https://doi.org/10.1111/j.1365-2125.1981.tb01304.x">Tucker, 1981</a>).
It can be defined as the product of renal plasma flow (<em>Q<sub>R</sub></em> ) and the renal
extraction ratio (<em>E<sub>R</sub></em> ):</p>
<p>Urinary clearance (<em>CL<sub>U</sub></em> ) of a drug or radiopharmaceutical is the virtual
volume of plasma from which drug is excreted to urine per unit time.
Urinary clearance can be calculated from the cumulative amount of drug excreted unchanged in
the urine (<em>A<sub>U</sub></em> ) up to time <em>T</em> and the <em>AUC</em> of
the plasma drug concentration
(<a href="https://doi.org/10.1111/j.1365-2125.1981.tb01304.x">Tucker, 1981</a>):</p>
<a name="eq_cl_r_1"></a>
<a name="eq_cl_r_2"></a>
<div class="eqs">
<script type="math/tex; mode=display">
\begin{equation}
CL_R = Q_R \times E_R
\end{equation}
</script>
<script type="math/tex; mode=display">
\begin{equation}
E_R = \small{1 - \frac{\text{Concentration of drug in renal venous plasma}}{\text{Concentration of drug in renal arterial plasma}}}
CL_U = \frac{A_U(T)}{AUC_{0-T}}
\end{equation}
</script>
</div>
<p>In practise, renal plasma clearance is often calculated from the cumulative amount of drug excreted
unchanged in the urine (<em>A<sub>U</sub></em> ) up to time <em>T</em> and the <em>AUC</em> of
the plasma drug concentration (<a href="https://doi.org/10.1111/j.1365-2125.1981.tb01304.x">Tucker, 1981</a>):</p>
<p>Similarly, the urinary clearance of a radiopharmaceutical can be defined as (metabolite corrected)
radioactivity in the urine (or bladder in the PET image) divided by the
<a href="./tac_auc.html">AUC</a> of blood (or plasma) curve. Since the blood curve is used,
the result is independent on other clearance routes, including uptake of radiopharmaceutical in
the tissues.</p>
<a name="eq_cl_r_2"></a>
<div class="eqs">
<script type="math/tex; mode=display">
\begin{equation}
CL_R = \frac{A_U(T)}{AUC_{0-T}}
\end{equation}
</script>
</div>
<p><a href="#kidneyfunction">Kidney function</a> is commonly assessed by measuring
<a href="./organ_kidney.html#renal_clearance">renal plasma clearance</a> of exogenous or endogenous
markers of glomerular and tubular filtration.
<a href="./organ_kidney.html#GFR">Glomerular filtration rate</a> (GFR) can be measured using markers
that are not secreted or reabsorbed by the <a href="./organ_kidney.html#tubular">tubular system</a>.
Urinary clearance considers only the marker entering the urine, while renal plasma clearance includes
also the possible renal retention of the marker.
Urinary clearance can be higher than GFR if the drug undergoes tubular secretion
(<a href="https://doi.org/10.1259/bjr.71.851.10434905">Peters, 1998</a>).</p>
<p>Similarly, the renal clearance (urinary clearance) of a radiopharmaceutical can be defined as
activity in the urine (or bladder in the image) divided by the <a href="./tac_auc.html">AUC</a> of
blood (or plasma) curve. Since the blood curve is used, the result is independent on other clearance
routes, including uptake of radiopharmaceutical in the tissues.</p>
<h3><a name="kidneyfunction">Kidney function</a></h3>
<p><a href="./organ_kidney.html#GFR">Glomerular filtration rate</a> is used as an index of
kidney function (renal function).
Radioligands that are not protein bound in the blood, and are not reabsorbed, secreted, or
metabolized in the <a href="./organ_kidney.html#tubular">renal tubular system</a>, can be used to
directly measure GFR. Error prone urinary collection can then be avoided, as
<a href="./organ_kidney.html#renal_clearance">renal plasma clearance</a> and
<a href="#urinary_clearance">urinary clearance</a> are equal, and GFR can be calculated from
a few plasma samples. Alternatively, ROIs drawn on the <a href="./organ_bladder.html">bladder</a>,
ureters, and <a href="./organ_kidney.html">kidneys</a> can be used
(<a href="https://doi.org/10.2967/jnumed.114.147843">Hofman et al., 2015</a>).</p>
<p>Urinary clearance of <a href="./analysis_18f-fluoride.html">[<sup>18</sup>F]fluoride</a> has been
used in rats to assess renal function noninvasively, with ROIs drawn on the heart cavity and
urinary bladder. The results correlated with traditional GFR estimation methods, even with variable
urine pH
<p>Several PET tracers for measuring GFR have been introduced, including
<a href="./analysis_68ga-dota.html">[<sup>68</sup>Ga]DOTA</a> and [<sup>68</sup>Ga]EDTA.
<a href="#urinary_clearance">Urinary clearance</a> of <a href="./analysis_18f-fluoride.html"
>[<sup>18</sup>F]fluoride</a> has been used in rats to assess renal function noninvasively, with
ROIs drawn on the heart cavity and urinary bladder. The results correlated with traditional GFR
estimation methods, even with variable urine pH
(<a href="https://doi.org/10.1007/s00259-008-0878-y">Schn&ouml;ckel et al., 2008</a>).
In humans, tubular reabsorption of [<sup>18</sup>F]F<sup>-</sup> is increased (renal clearance is
reduced) with decreased urine flow
......@@ -169,37 +178,6 @@ that the method may not be reliable for estimating
<h3><a name="kidneyfunction">Kidney function</a></h3>
<p><a href="./organ_kidney.html#GFR">Glomerular filtration rate</a> (<em>GFR</em> ) is used as an
index of <a href="./organ_kidney.html#renal_function">kidney function</a>.
Radioligands that are not protein bound in the blood, and are not reabsorbed, secreted, or
metabolized in the renal tubular system, can be used to directly measure <em>GFR</em>.
If the fraction of unbound drug in plasma (<em>f<sub>U</sub></em> ) is known, <em>GFR</em> and
<em>CL<sub>R</sub></em> are related by equation</p>
<a name="eq_gfr"></a>
<div class="eqs">
<script type="math/tex; mode=display">
\begin{equation}
CL_R = f_U \times {GFR}
\end{equation}
</script>
</div>
<p>While it is generally considered that only free drug in plasma can be excreted to urine,
plasma protein bound drug and/or drug in erythrocytes may also be available for tubular excretion,
if equilibration of free drug in plasma between these components is rapid.</p>
<p>Several PET tracers for measuring GFR have been introduced, including
<a href="./analysis_68ga-dota.html">[<sup>68</sup>Ga]DOTA</a> and [<sup>68</sup>Ga]EDTA.
Error prone urinary collection can be avoided, when radioligand is only eliminated via glomerular
filtration, and plasma and urinary clearances are thus equal; GFR can then be calculated from
a few plasma samples. Alternatively, ROIs drawn on the <a href="./organ_bladder.html">bladder</a>,
ureters, and <a href="./organ_kidney.html">kidneys</a> can be used
(<a href="https://doi.org/10.2967/jnumed.114.147843">Hofman et al., 2015</a>).</p>
<h2><a name="dose">Radiation dose</a></h2>
......
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