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

Dear Rob, A few comments to your message: In a PharmPK thread in 2013, cited by you, Nick Holford explained his approach for using estimates of GFR for dose adjustment, in answer to a message from myself, suggesting an approach suggested long time ago by Dettli and others. This can be written as: CL_renal_drug = fr * eGFR where CL_renal_drug is the renal clearance of the drug (in ml/min), fr is the (dimensionless) ratio of renal clearance of the drug (assumed to be drug-specific, but independent of GFR), eGFR is the estimated value for GFR (irrespective of the method, expressed in ml/min, not ml/min/1.73m2). As far as I know, there is no literature comparing both approaches, so it remains to be determined which approach is 'best'. You are completely right that it may be questioned whether this holds for drugs that are actively secreted. For the latter, an additional clerance term may be added, using allometric scaling with exponent 0.75. The CKD-EPI equation does not contain any measure of body size. This is not really surprising, since GFR is expressed in ml/min/1.73m2. This value is scaled for body surface area, which is rather close to allometric scaling with a factor of 0.75. The eGFR expressed in ml/min, which is an estimate of the actual GFR, is affected by weight and height, as expected. Note that eGFR expressed in ml/min/1.73m2 is used by nephrologists as a measure of renal function, but for estimation of renal clearance and dosing purposes, one should always use eGFR in ml/min. For example, the Dettli approach can be used for any estimate of eGFR, provided that values in ml/min/1.73m2 are converted to ml/min, using the body surface area estimated from weight and height. best regards, Johannes H. Proost Department of Pharmacokinetics, Toxicology and Targeting University of Groningen the Netherlands Op 5-12-2017 om 18:17 schreef [email protected]: > 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.