A Population Pharmacokinetic Model for 51 Cr EDTA to Estimate Renal Function

• Published in: Clinical pharmacokinetics Vol. 56; no. 6; p. 671
• Main Authors: Kuan, Isabelle H S, Duffull, Stephen B, Putt, Tracey L, Schollum, John B W, Walker, Robert J, Wright, Daniel F B
• Format: Journal Article
• Language: English
• Published: Switzerland 01.06.2017
• Subjects: Adult; Aged; Aged, 80 and over; Chromium Radioisotopes; Edetic Acid - blood; Edetic Acid - pharmacokinetics; Female; Glomerular Filtration Rate; Humans; Kidney - physiology; Kidney Diseases - blood; Kidney Diseases - physiopathology; Male; Models, Biological; Young Adult

Cr EDTA clearance (CL) from plasma is used to estimate glomerular filtration rate (GFR). We propose that current methods for analysing the raw Cr EDTA measurements over-simplifies the disposition of Cr EDTA and therefore could produce biased GFR estimates. The aim of this study was to develop a population pharmacokinetic model for Cr EDTA disposition and to compare model-predicted GFR to other methods of estimating renal function. Data from 40 individuals who received ~7.4 MBq of Cr EDTA, as an intravenous bolus, were available for analysis. Plasma radioactivity (counts/min) was measured from timed collection points at 2, 4, 6 and 24 h after the dose. A population analysis was conducted using NONMEM version 7.2. Model-predicted GFR was compared with other methods for estimating renal function using mean prediction error (MPE). A two-compartment pharmacokinetic model with first-order elimination best fit the data. Compared with the model predictions, creatinine CL from 24 h urine data was unbiased. The commonly used 'slope-intercept' method for estimating isotopic GFR was positively biased compared with the model (MPE 15.5 mL/min/1.73 m [95% confidence interval {CI} 8.9-22.2]. The Cockcroft Gault, Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-Epi) equations led to negatively biased GFR estimates (MPE -19.0 [95% CI -25.4 to -12.7], -20.1 [95% CI -27.2 to -13.1] and -16.5 [95% CI -22.2 to -10.1] mL/min/1.73 m , respectively). The biased GFR estimates were most obvious in patients with relatively normal renal function. This may lead to inaccurate dosing in patients who are receiving drugs with a narrow therapeutic range where dosing is adjusted according to GFR estimates (e.g. carboplatin). The study is registered with the Australian New Zealand Clinical Trials Registry (ANZCTR), number: ACTRN 12611000035921.