|Home | About | Journals | Submit | Contact Us | Français|
Giles and Fitzmaurice did not discuss another use of estimated renal function—to guide changes in the dosage regimens of drugs that are eliminated unchanged by the kidneys, that have active metabolites that are eliminated by the kidneys, or whose pharmacodynamic effects are affected by renal insufficiency.1 This is particularly important for drugs that have a low therapeutic index.
Recommendations about drug dosage regimens given in manufacturers' summaries of product characteristics and in secondary sources, such as the British National Formulary, are based on creatinine clearance. It is therefore customary when altering dosage regimens in renal insufficiency to estimate glomerular filtration rate (GFR) by using calculated creatinine clearance, usually derived from the Cockcroft-Gault equation for adults2 or the Schwartz-Haycock equation for children.3
The eGFR estimated by the modified four variable modification of diet in renal disease (MDRD) equation underestimates true GFR more than the Cockcroft-Gault equation does in younger patients and less in older patients; overall, MDRD underestimates true GFR more than Cockcroft-Gault does.4 There are further differences in critically ill patients with burns.5 There is currently no information on how to use the eGFR to calculate changes in drug dosage regimens.
Clinical biochemistry laboratories would help doctors if they reported not only the MDRD-derived eGFR in ml/min/1.73 m², but also the Cockcroft-Gault estimated creatinine clearance in ml/min/70 kg, for which only the age and sex of the patient are needed (and not also ethnic group, as for eGFR). General practitioners could programme the appropriate equations into their computerised records.
Dosage changes that are made on the basis of any surrogate measure of GFR should be regarded as initial estimates. Further changes should be made, if necessary, through careful monitoring of beneficial and adverse effects by measuring clinical progress, or pharmacodynamic biomarkers of the actions of the drug, or serum drug concentrations, as relevant.
Competing interests: JKA is a member of the Joint Formulary Committee of the BritishNational Formulary and the Paediatric Formulary Committee of the British NationalFormulary for Children. However, the opinions expressed here do not necessarily reflect those of other members of those committees.