Kidney international reports · 2026
Impact of mGFR Versus eGFR on the Pharmacokinetics of a Renally Excreted Model Drug in Older Medical Patients: A Proof-of-Concept Trial.
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Storgaard Ida K, Houlind Morten B, Christensen Louise Ws, Nielsen Rikke L, Andersen Aino L, Bornæs Olivia, Juul-Larsen Helle G, Dang Johnny K H, Jawad Baker N, Altintas Izzet, Tavenier Juliette, Porrini Esteban, Iversen Esben, Damgaard Morten, Andersen Ove, Hornum Mads, Lund Trine M
Аннотация
INTRODUCTION: Accurate assessment of kidney function is essential for dosing renally eliminated drugs, such as gentamicin. However, creatinine-based estimated glomerular filtration rate (eGFR) equations may be inaccurate in older adults because creatinine concentrations are influenced by nonrenal factors, including reduced muscle mass and frailty. This study investigated whether measured GFR (mGFR) and 10 different eGFR equations improve the modeling of gentamicin renal clearance, used as a model compound for renally eliminated drugs, when included as covariates in a population pharmacokinetic (popPK) model of older medical patients with poor appetite.
METHODS: This prospective diagnostic accuracy and population pharmacokinetic study evaluated mGFR determined by 99mTc-DTPA plasma clearance and 10 eGFR equations on the basis of plasma creatinine, cystatin C, β2-microglobulin, and/or β-trace protein. Poor appetite was assessed using the Simplified Nutritional Appetite Questionnaire (SNAQ). Plasma gentamicin concentrations were measured over 22 hours after a single i.v. dose of 5 mg/kg. Gentamicin concentration-time profiles were analyzed using nonlinear mixed-effects modeling. Improvement in model performance was assessed by changes in objective function value (OFV) and interindividual variability (IIV) in clearance.
RESULTS: A total of 52 older medical patients with poor appetite (median age 79.5 [interquartile range, {IQR} 73.0-84.3] years, 56% female, median SNAQ score 12 [IQR 11-13]) were included. mGFR expressed in ml/min provided the greatest improvement in model fit when included as a covariate for gentamicin clearance (-ΔOFV = 115.00). Among eGFR equations, combined creatinine-cystatin C equations expressed in ml/min yielded the best performance (-ΔOFV = 72.58-77.11), whereas creatinine-only equations showed the poorest improvement (-ΔOFV < 63.69). Overall, absolute GFR estimates performed better than body surface area-indexed estimates.
CONCLUSIONS: Creatinine-only eGFR equations may be suboptimal proxies for gentamicin clearance in this patient population. If measuring GFR is unfeasible, estimating GFR on the basis of a combination of creatinine and cystatin C is the best alternative.
METHODS: This prospective diagnostic accuracy and population pharmacokinetic study evaluated mGFR determined by 99mTc-DTPA plasma clearance and 10 eGFR equations on the basis of plasma creatinine, cystatin C, β2-microglobulin, and/or β-trace protein. Poor appetite was assessed using the Simplified Nutritional Appetite Questionnaire (SNAQ). Plasma gentamicin concentrations were measured over 22 hours after a single i.v. dose of 5 mg/kg. Gentamicin concentration-time profiles were analyzed using nonlinear mixed-effects modeling. Improvement in model performance was assessed by changes in objective function value (OFV) and interindividual variability (IIV) in clearance.
RESULTS: A total of 52 older medical patients with poor appetite (median age 79.5 [interquartile range, {IQR} 73.0-84.3] years, 56% female, median SNAQ score 12 [IQR 11-13]) were included. mGFR expressed in ml/min provided the greatest improvement in model fit when included as a covariate for gentamicin clearance (-ΔOFV = 115.00). Among eGFR equations, combined creatinine-cystatin C equations expressed in ml/min yielded the best performance (-ΔOFV = 72.58-77.11), whereas creatinine-only equations showed the poorest improvement (-ΔOFV < 63.69). Overall, absolute GFR estimates performed better than body surface area-indexed estimates.
CONCLUSIONS: Creatinine-only eGFR equations may be suboptimal proxies for gentamicin clearance in this patient population. If measuring GFR is unfeasible, estimating GFR on the basis of a combination of creatinine and cystatin C is the best alternative.