BMJ  2007;334:1287 (23 June), doi:10.1136/bmj.39247.716806.3A

Letters

Glomerular filtration rate

eGFR in changing drug regimens

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.

Department of Clinical Pharmacology, Radcliffe Infirmary, Oxford OX2 6HA

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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.

References

1. Giles PD, Fitzmaurice DA. Formula estimation of glomerular filtration rate: have we gone wrong? BMJ 2007;334:1198-200. (9 June.)[Free Full Text]
2. Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 1976; 16: 31-41.
3. Schwartz GJ, Haycock GB, Edelmann CM Jr, Spitzer A. A simple estimate of glomerular filtration rate in children derived from body length and plasma creatinine. Pediatrics 1976; 58: 259-63.
4. Verhave JC, Fesler P, Ribstein J, du Cailar G, Mimran A. Estimation of renal function in subjects with normal serum creatinine levels: influence of age and body mass index. Am J Kidney Dis 2005;6:233-41.
5. Conil JM, Georges B, Fourcade O, Seguin T, Lavit M, Samii K, et al. Assessment of renal function in clinical practice at the bedside of burn patients. Br J Clin Pharmacol 2007;63:583-94.[CrossRef][ISI][Medline]

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Relevant Article

Formula estimation of glomerular filtration rate: have we gone wrong?

Paul D Giles and David A Fitzmaurice
BMJ 2007 334: 1198-1200. [Extract] [Full Text] [PDF]