Estimation of glomerular filtration rate in cancer patients

Abstract

The frequent need to obtain an estimate of renal function in cancer patients, not least for targeting carboplatin dose, has led to a number of approaches to estimate glomerular filtration rate (GFR). This study aimed to develop a simple and reliable method to estimate GFR using readily-available patient characteristics. Data from 62 patients with estimates of 51 Cr-EDTA clearance were analysed to determine the most appropriate formula relating this method of measuring GFR to patient characteristics. The population pharmacokinetics of 51 Cr-EDTA were analysed using NONMEM to evaluate the influence of each covariate. The formulae derived were then validated using a further 38 patients and compared with those obtained using existing formulae 51 Cr-EDTA clearance (GFR) was positively related to Dubois surface area, negatively related to age, and inversely related to serum creatinine (SCr). Females had lower 51 Cr-EDTA clearance than males. The enzymatic method of SCr assay gave more reliable results than the Jaffe colorimetric method. A measure of creatine kinase significantly improved the estimation of GFR. The new formula produced estimates of GFR which were less biased (Mean Prediction Error = –3%) and more precise (Mean Absolute Prediction Error = 12%) than Cockcroft and Gault (–8% and 16%) or Jelliffe (–15% and 19%) estimates. The formulae developed here can be used to provide reliable estimates of GFR, particularly in regard to targeted dosing of carboplatin. © 2001 Cancer Research Campaign http://www.bjcancer.com

Estimation of glomerular filtration rate in paediatric cancer patients using 51CR-EDTA population pharmacokinetics

“…The abilities of these models to predict GFR were compared with the functional form of previously published creatinine clearance models. This type of population pharmacokinetic approach for predicting GFR has previously been used successfully in adults (Martin et al, 1998;Wright et al, 2001) and in children with renal disease (Léger et al, 2002). 51 Cr-EDTA clearance was strongly correlated to body size, with a simple additive model (16.25 þ 1.67 Â Wt) proving to be as good a fit as that obtained using more complex transformations of BSA and weight.…”

“…For this reason, approaches based on nonlinear mixed effects models, often referred to as population models, have recently been published and independently assessed (Martin et al, 1998;Wright et al, 2001;Poole et al, 2002;Léger et al, 2002). These methods involve the use of patient specific 51 Cr-EDTA plasma data together with supplementary covariate information.…”

Impact of renal impairment on eligibility for adjuvant cisplatin‐based chemotherapy in patients with urothelial carcinoma of the bladder

“…Whereas the CG equation is utilized in most clinical trials, and recognized by the Food and Drug Administration (FDA) in studies of patients with renal impairment, 29 other formulas have been proposed as more applicable for use in cancer patients. 30 For example, in a study of 116 ovarian cancer patients, Calvert et al 31 reported that GFR determined by chromium-51-EDTA clearance had correlation coefficients of 0.75 with the Jelliffe and 0.65 with the CG formula estimates of CrCl. More recently, investigators have called for exploration of the MDRD study equation in oncology trials.…”

Performance of formulae based estimates of glomerular filtration rate for carboplatin dosing in stage 1 seminoma

“…Ainsworth et al studied the performance of the CG and MDRD equations in a larger oncology cohort, as well as investigating the accuracy of the Wright and Jeliffe equations, which were specifically derived from oncology cohorts (21)(22)(23).…”