New Model for Estimating Glomerular Filtration Rate in Patients With Cancer.

Tobias Janowitz,Andrea Marshall,Peter B Thomas,Jeff White,Simon Tavaré,Andy G Lynch,Edward H Williams,Nicola Ainsworth,Helena Earl,Duncan I Jodrell,Scott Shepherd,Stephen J Sammut,Patrick B Mark

doi:10.1200/jco.2017.72.7578

Abstract

PurposeThe glomerular filtration rate (GFR) is essential for carboplatin chemotherapy dosing; however, the best method to estimate GFR in patients with cancer is unknown. We identify the most accurate and least biased method.MethodsWe obtained data on age, sex, height, weight, serum creatinine concentrations, and results for GFR from chromium-51 (51Cr) EDTA excretion measurements (51Cr-EDTA GFR) from white patients ≥ 18 years of age with histologically confirmed cancer diagnoses at the Cambridge University Hospital NHS Trust, United Kingdom. We developed a new multivariable linear model for GFR using statistical regression analysis. 51Cr-EDTA GFR was compared with the estimated GFR (eGFR) from seven published models and our new model, using the statistics root-mean-squared-error (RMSE) and median residual and on an internal and external validation data set. We performed a comparison of carboplatin dosing accuracy on the basis of an absolute percentage error > 20%.ResultsBetween August 2006 and January 2013, data from 2,471 patients were obtained. The new model improved the eGFR accuracy (RMSE, 15.00 mL/min; 95% CI, 14.12 to 16.00 mL/min) compared with all published models. Body surface area (BSA)–adjusted chronic kidney disease epidemiology (CKD-EPI) was the most accurate published model for eGFR (RMSE, 16.30 mL/min; 95% CI, 15.34 to 17.38 mL/min) for the internal validation set. Importantly, the new model reduced the fraction of patients with a carboplatin dose absolute percentage error > 20% to 14.17% in contrast to 18.62% for the BSA-adjusted CKD-EPI and 25.51% for the Cockcroft-Gault formula. The results were externally validated.ConclusionIn a large data set from patients with cancer, BSA-adjusted CKD-EPI is the most accurate published model to predict GFR. The new model improves this estimation and may present a new standard of care.

Highlights

The glomerular filtration rate (GFR), the fluid volume filtered from the capillaries of the renal glomeruli into the Bowman’s capsule per unit time, is used for calculations of carboplatin chemotherapy doses.[1]
We developed a new multivariable linear model for GFR using statistical regression analysis. 51Cr-EDTA GFR was compared with the estimated GFR from seven published models and our new model, using the statistics root-mean-squared-error (RMSE) and median residual and on an internal and external validation data set
The new model improved the estimated GFR (eGFR) accuracy (RMSE, 15.00 mL/min; 95% CI, 14.12 to 16.00 mL/min) compared with all published models

Summary

Introduction

The glomerular filtration rate (GFR), the fluid volume filtered from the capillaries of the renal glomeruli into the Bowman’s capsule per unit time, is used for calculations of carboplatin chemotherapy doses.[1]. Models for GFR estimation have been developed on the basis of readily available data, such as serum creatinine concentrations, age, and sex of the patient.[3,4,5,6,7,8,9,10,11]. These published models for GFR have been mainly developed for noncancer patient populations that are frequently enriched for patients with chronic kidney disease. Their usefulness in patients with cancer has been examined using only small data sets, and limitations have been documented.[12,13,14,15,16]

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Conclusion