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Kidney volume calculation #360

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Jesminna opened this issue Jul 16, 2019 · 17 comments

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@Jesminna
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commented Jul 16, 2019

Hello,

Based on the information in the literature (https://www.ncbi.nlm.nih.gov/pubmed/26323410), it looks like the attached equation is used in PKSim for GFR calculation. Is there any equation used in PKSim for kidney volume calculation? If yes, could you share the equation?

Thanks!

Jesminna
GFR equation

@PavelBal

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commented Jul 16, 2019

Hello Jesminna,

you can see all the equations if you export the model to MoBi:

image

There you will find a tree of the whole organism in the Spatial Stuctures Building Block, where you can see how the parameters are defined.

image

The volume of the kidney is a distributed parameter with a mean value and standard deviation. For a mean individual, the volume is taken from the PK-Sim database according to the anthropomentry you selected for the indiidual.

@Jesminna

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commented Jul 16, 2019

Thank you! I found a few equations in literature which was used for kidney volume calculation based on the body weight or kidney weight. The calculated kidney volume is smaller than the data provided in PKSim. Could you share the literature which PKSim uses to generate the mean individual kidney volume data. Thanks!

@msevestre

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commented Jul 17, 2019

@Jesminna

Could you share the literature which PKSim uses to generate the mean individual kidney volume data.

This depends on the population selected when creating the individual

image

Let me know if that helps,
Michael

@Jesminna

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commented Jul 17, 2019

I would like to know the reference for preterm infants. Thanks!

@Incei

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commented Jul 17, 2019

I would like to know the reference for preterm infants. Thanks!

Here is the reference link: https://www.ncbi.nlm.nih.gov/pubmed/26323410
Cheers

@Incei

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commented Jul 17, 2019

@Yuri05 @msevestre it may be a good idea to add (Claassen 2015) behind the 'Preterm' population.

@Jesminna

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commented Jul 17, 2019

@Incei

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commented Jul 17, 2019

@Jesminna I cannot see the image, which cited article do you refer to?

In case you mean reference 35 (Basic anatomical and physiological data for use in radiological protection: reference values: ICRP Publication 89: Approved by the Commission in September 2001), information on kidney volume is mentioned there..
Based on the ICRP data, an adult pbpk model for Europeans (ICRP2002) was created and kidney volume was calculated and reported in: https://www.ncbi.nlm.nih.gov/pubmed/17431751 : Development of a Physiology-Based Whole-Body Population Model for Assessing the Influence of Individual Variability on the Pharmacokinetics of Drugs

This is the (rounded) adult 440mg kidney volume where the Claassen 2015 et al refers to for the modified GFR function.

Hope this helps!

@Yuri05

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commented Jul 17, 2019

@Jesminna

I cannot see the image in your last comment (when attaching images or files, please do it directly on GitHub. If you answer to an notification email - attachments are lost).

But I guess you refer to this part of (Claassen 2015)?
grafik

If so, you will find reference for kidney weights on page 6(261) of the referenced article
We assume density=1, thus volume(kidney)=weight(kidney).

EDIT: if you ask about ADULT kidney volume used for GFR calculation, then reply by @Incei above applies.

@Jesminna

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commented Jul 17, 2019

Thank you! I appreciate it. Based on the data in fig 11 in the reference article (Quantitative Standards for Fetal and Neonatal Autopsy), it seems that the kidney volume values are smaller than those provided in PKSim. For example, the kidney volume in fig 11 for a 40 weeks PMA baby is around 25 mL (25g), whereas the kidney volume provided in PKSim for a 40 weeks PMA baby is 38.6 mL. The calculated GFR would be around 1.89 (based on a kidney volume of 25 mL) and 3.52 (based on a kidney volume of 38.6) ml/min.

@Jesminna

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commented Jul 17, 2019

Any comments on the difference between literature reported and PKSim provided kidney volume data? or is there any other factor that needs to be considered? Thanks!

@JanSchlender

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commented Jul 21, 2019

Hi Jesminna,
Your last post was already pointing in the right direction. Within the method section of Claasen's publication, the conversion from postmortem autopsy measures to perfused organ sizes is described and referenced ("Furthermore, all organ weights summarized in this article refer to exsanguinated organs and require correction for their blood content, as already described by Edginton et al. in order to obtain the total in vivo organ weight [Edginton AN, Schmitt W, Willmann S. Development and evaluation of a generic physiologically based pharmacokinetic model for children. Clin Pharmacokinet 2006; 45(10): 1013-34]"). In short, a vascular fraction is added to the autopsy weight. Literature sources for these fractions can be found in the aforementioned source.
The GFR, resulting from from the perfused kidney, is then well in line with the reported literature for this parameter.
Best,
Jan

@Jesminna

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commented Jul 21, 2019

Thanks a lot, Jan, for the detailed information! I was trying to calculate the kidney volume by adding the blood content to the kidney weight, however, I still cannot get the kidney volume data provided in the PKSim. Could you please help with this calculation? The following is my calculation.

The fraction of vascular space in kidney listed in Table II in Edginton 2006 article is 0.23. Since there is no evidence of age-dependence for the organ vascular space, the blood content in a newborn baby kidneys equals 0.23*270=62.1 mL. The number of 270 is the total blood volume in a newborn baby from Annals of the ICRP 89. Apparently the number of 62.1 mL is too big. Could you help with this calculation?

In addition, the total fraction of vascular space (2.19) showed in Table II in Edginton 2006 article is greater than 1. I do not quite understand it. Could you share your comments on this?
Thanks!

@prvmalik

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commented Jul 21, 2019

The vascular fraction of each organ is the fraction of total organ volume attributed to vascular space.

It is NOT the fraction of total blood volume that is residing in the organ at any given time, as you have explained.

In Table II in Edginton 2006 each organ is assigned a vascular fraction and an interstitial fraction (along with relevant age dependencies as defined) such that:

Fv x V + Fi x V + Fc x V = V

where V is the total organ volume for an individual organ
Fv is the vascular fraction
Fi is the interstitial fraction
and Fc is the cellular fraction

In other words, for each individual organ, Fv + Fi + Fc always add up to 1.

In the case of the kidney, a vascular fraction of 0.23 means that 23% of the organ volume is blood/vascular volume.

@Jesminna

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commented Jul 22, 2019

On page 1016 in Edginton 2006, there is an explanation about how to obtain the vascular space that "the vascular space of each organ was calculated from its blood content, taken as a percentage of total blood volume in adult". Did I miss anything?

In addition, based on your explanation, can I use the following equation to calculate kidney volume assuming density=1?

Kidney volume=0.23*Kidney volume + Kidney weight

The calculated kidney volume for a 40 weeks PMA baby is 33 mL. The Kidney volume in PKSim is 38.6 mL.

@tobiasK2001

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commented Jul 22, 2019

Dear Jesminna,

I think the calcaltion should like prvmalik pand Jan pointed out more like this:
V(kidney)= 38.6 ml = 0.23(fraction vascular) x 38.6+0.57(fraction intracellular) x 38.6+0.2(fraction interstistial) x 38.6
B.t.w. the vascular and interstitial fraction for each organ in PK-sim can be found here:
image

According to this the "perfused kidney tissue" volume (, without the fraction vascular) would be: 0.57(fraction intracellular) x 38.6+0.2(fraction interstistial) x 38.6 = 0.77 x 38.6= 29.7 ml

Assuming a density = 1 this would give 27.9 g perfused tissue weight. Using that value the GFR should be in range with reported values.

Did that solve your question?

Best, Tobias

@Jesminna

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commented Jul 22, 2019

Thank you, Tobias! I have to go back to my original question regarding how to calculate kidney volume or where I can find the kidney volume data. your calculation was based on the known kidney volume.

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