Utility, or not, of estimates of glomerular filtration rate in modifying drug dosage, with particular reference to enoxaparin

Abstract

A reduced clearance of some drugs in renal failure is a problem, particularly with drugs that are excreted by the kidney substantially unmetabolised and also have significant toxicity and a low therapeutic ratio. The problem is compounded by the significant inaccuracy of estimated glomerular filtration rate (eGFR). The aim was to develop general recommendations to reduce the risk of drug toxicity in renal failure, with particular reference to enoxaparin. The substantial inaccuracies in eGFR (eGFR in 32% of patients is different from measured GFR by 20-30%) are compounded when using a dichotomous decision tree (renal failure or not). As the eGFR approaches the GFR decision boundary, for classification as renal failure or not, misclassification approaches 50%. Recommendations, when patients are at risk, include the following: acknowledge inaccuracies of eGFR, particularly in anthropometrically diverse populations; measure drug levels wherever possible; realise that drug levels after early doses relate more to volume of distribution, rather than renal function, allowing time for modification of the drug dose; where accurate urine collection is feasible, use creatinine clearance as an estimate of GFR; and use eGFR as a (more) continuous, rather than dichotomous, variable to adjust dosage, exampled by enoxaparin.