EVALUATING PREDICTION METHODS FOR GLOMERULAR FILTRATION TO OPTIMISE DRUG DOSES IN OBESE AND NON-OBESE PATIENTS.
The most suitable method for predicting the glomerular filtration rate (GFR) in obesity is currently debated. Therefore, multiple GFR/creatinine clearance prediction methods were applied to (morbidly) obese and non-obese patients ranging from moderate renal impairment to glomerular hyperfiltration and their predictions were rated based on observed fosfomycin pharmacokinetics, as model drug being exclusively eliminated via glomerular filtration. The GFR/creatinine clearance predictions via the CKD-EPI, MDRD (indexed and de-indexed by body surface area), and creatinine clearance via the Cockcroft-Gault formula (CLCR ) using different body size descriptors were compared to the fosfomycin clearance (CL ) from 30 surgical patients (BMI=20.1-52.0 kg·m ), receiving 8000 mg as intravenous infusion. The concordance between CL and creatinine clearance predictions was highest for CLCR employing either ideal body weight (IBW) or adjusted body weight (if body mass >1.3·IBW) (CLCR , concordance-correlation-coefficient [95% CI=0.474 [0.156; 0.703], CCC) and GFR predictions via the de-indexed MDRD equation (CCC=0.452 [0.137; 0.685]). The proportion of predicted GFR values within ±30% of the observed CL (P =72.3%-76.7%) was only marginally lower than the reported P in the original CKD-EPI and MDRD publications (P =84.1%-90.0%). This analysis represents a successful proof-of-concept for evaluating GFR/creatinine clearance prediction methods: Across all BMI-classes CLCR or the de-indexed MDRD were most suitable for predicting creatinine clearance/GFR also in (morbidly) obese, CKD stage <3B individuals in therapeutic use. Their application is proposed in optimising doses for vital therapies in obese patients requiring monitoring of renal function (e.g. methotrexate dosing).This article is protected by copyright. All rights reserved.