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Re: [NMusers] Allometric scaling of renal clearance with estimated glomerular filtration rate

From: <R.terHeine_at_radboudumc.nl>
Date: Wed, 6 Dec 2017 10:52:32 +0000

Hi Ruben,

Interesting work, Ruben. One may indeed question the validity of glomerular filtration rate markers like cystatin C (that is only filtrated and not actively secreted) to predict PK of drugs that undergo active tubular secretion in patients with decreased renal function. When glomerular filtration rate drops, the relative contribution of active tubular secretion to renal clearance increases. To me, it appears logical that creatinine is a better marker for clearance drugs that are actively secreted, as creatinine also undergoes active tubular secretion.

Nonetheless, I’m also interested whether other people have considered allometric scaling of MDRD/CKD-EPI derived GFR’s?

Cheers,
Rob
Van: Ruben Faelens <ruben.faelens_at_gmail.com>
Datum: dinsdag 5 december 2017 om 7:13 PM
Aan: "Heine, Rob ter" <R.terHeine_at_radboudumc.nl>
CC: "nmusers_at_globomaxnm.com" <nmusers_at_globomaxnm.com>
Onderwerp: Re: [NMusers] Allometric scaling of renal clearance with estimated glomerular filtration rate


Dear Rob,

At PMX Benelux, there was an interesting talk about the correlation between different metrics describing renal function by Stijn Jonckheere.
A part of the work presented was published: https://academic.oup.com/jac/article/71/9/2538/1750427

This may provide some perspective, or rather complicate things even more, depending on your viewpoint.

Best regards
Ruben Faelens

Op di 5 dec. 2017 18:24 schreef <R.terHeine_at_radboudumc.nl<mailto:R.terHeine_at_radboudumc.nl>>:
Dear all,

I am wondering what your thoughts are on the allometric scaling of clearance of renally extreted drugs, where we have estimations renal function.

Simply scaling the predicted glomerular filtration rate from, for example, the Cockroft-gault equation seems inappropriate, since weight is already a part of the equation. Standardizing this to weight in the Cockroft-gault equation can be done, a solution has been discussed here: http://cognigencorp.com/nonmem/current/2013-August/4697.html

However, in the recent years some new equations to calculate glomerular filtration rate from endogenous markers have emerged. For example the CKD-EPI CREATININE CYSTATIN C equation https://www.kidney.org/content/ckd-epi-creatinine-cystatin-equation-2012 . As the addition of a muscle mass independent endogenous marker like cystatin C is known to provide better estimations of GFR in, for example, cachectic patients, it is likely that this equation may outperform to predict renally filtrated compounds in this patient group. It is rather odd that this CKD-EPI equation does not contain any measure of body size. The outcome of this equation is a GFR scaled to a BSA of 1.73m^2.

I am wondering how you would allometrically scale the eGFRs from these CKD EPI equations to, for example, fat-free mass.

Cheers!
Rob

R. ter Heine, PhD, PharmD
Hospital Pharmacist-Clinical Pharmacologist
Radboudumc, Nijmegen, The Netherlands


Het Radboudumc staat geregistreerd bij de Kamer van Koophandel in het handelsregister onder nummer 41055629.
The Radboud university medical center is listed in the Commercial Register of the Chamber of Commerce under file number 41055629.

Het Radboudumc staat geregistreerd bij de Kamer van Koophandel in het handelsregister onder nummer 41055629.
The Radboud university medical center is listed in the Commercial Register of the Chamber of Commerce under file number 41055629.

Received on Wed Dec 06 2017 - 05:52:32 EST

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