Overestimation of carboplatin doses is avoided by radionuclide GFR measurement

Abstract

Background: Glomerular filtration rate (GFR) is used in the calculation of carboplatin dose. Glomerular filtration rate is measured using a radioisotope method (radionuclide GFR (rGFR)), however, estimation equations are available (estimated GFR (eGFR)). Our aim was to assess the accuracy of three eGFR equations and the subsequent carboplatin dose in an oncology population.

Patients and methods: Patients referred for an rGFR over a 3-year period were selected; eGFR was calculated using the Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Cockcroft-Gault (CG) equations. Carboplatin doses were calculated for those patients who had received carboplatin chemotherapy. Bias, precision and accuracy were examined.

Results: Two hundred and eighty-eight studies met the inclusion/exclusion criteria. Paired t-tests showed significant differences for all three equations between rGFR and eGFR with biases of 12.3 (MDRD), 13.6 (CKD-EPI) and 7.7 ml min(-1) per 1.73 m(2) (CG). An overestimation in carboplatin dose was seen in 81%, 87% and 66% of studies using the MDRD, CKD-EPI and CG equations, respectively.

Conclusion: The MDRD and CKD-EPI equations performed poorly compared with the reference standard rGFR; the CG equation showed smaller bias and higher accuracy in our oncology population. On the basis of our results we recommend that the rGFR should be used for accurate carboplatin chemotherapy dosing and where unavailable the use of the CG equation is preferred.

Figure 1

Scatter plots of rGFR plotted against (A) the eGFR calculated from the MDRD equation, (B) the eGFR calculated from the CKD-EPI equation and (C) the eGFR calculated from the CG equation. The linear regression lines are shown as solid lines, the lines of identity are shown as dashed lines.

Figure 2

Bland-Altman plots of the difference of the eGFR and the rGFR against the mean of the eGFR and the rGFR. The 95% limits of agreement are represented by the dashed lines, the lines of bias are represented by the solid lines. These are shown for (A) the MDRD eGFR (bias 12.3 ml min⁻¹ per 1.73 m²; 95% confidence limits −17.8 : 42.3 ml min⁻¹ per 1.73 m²), (B) the CKD-EPI eGFR (bias 13.6 ml min⁻¹ per 1.73 m²; 95% confidence limits −15.0 : 42.2 ml min⁻¹ per 1.73 m²) and (C) the CG eGFR (bias 7.7 ml min⁻¹ per 1.73 m²; 95% confidence limits −25.2 : 40.6 ml min⁻¹ per 1.73 m²).

Figure 3

Bland-Altman plots of the difference of the carboplatin dosing against the mean of the carboplatin dosing calculated from the eGFR and the rGFR. The 95% limits of agreement are represented by the dashed lines, the lines of bias are represented by the solid lines. These are shown for (A) the MDRD eGFR (bias 61.0 mg; 95% confidence limits −92.4 : 214.4 mg), (B) the CKD-EPI eGFR (bias 70.7 mg; 95% confidence limits −71.1 : 212.6 mg) and (C) the CG eGFR (bias 45.1 mg; 95% confidence limits −133.6 : 223.8 mg).