Drug dosing adjustment in people with reduced GFR

Editor, – The article'Prescribing in renal disease' (Aust Prescr 2007;30:17-20) is a useful contribution to the complex issues currently facing prescribers. There is wide agreement that determining kidney function by measurement or assessment of glomerular filtration rate (GFR) is preferable to using the serum creatinine alone, for all clinical purposes (including drug dosing).

The vast majority of prescribing in Australian general practice occurs without knowledge of the patient's kidney function. When an assessment of kidney function is available it is now usually in the form of an automatically generated eGFR (estimated GFR) derived from the Modification of Diet in Renal Disease (MDRD) study. Few, if any, practitioners routinely calculate GFR by using the Cockcroft-Gault equation or measure creatinine clearance on all patients.

After considering these matters, a meeting of the Australian Creatinine Consensus Working Group agreed that the following recommendation should be promoted to Australian prescribers:

Decision making in drug dose adjustment in people with chronic kidney disease is enhanced by an assessment of kidney function based on GFR rather than a serum creatinine concentration alone. In most out-of-hospital settings (particularly general practice) where an eGFR (MDRD) is on hand and no other measure of GFR is known or readily accessible, it is clinically appropriate to use eGFR to assist drug dosing decision making.

However, for critical dose drugs, particularly in a hospital setting, it remains important to adhere to the published recommendations that usually involve the use of the Cockcroft-Gault equation to estimate GFR, or to measure creatinine clearance in order to amend dosing for renal function.

The product information guiding dose adjustment in patients with reduced GFR is often permeated with imprecise and undefined terminology (such as renal impairment, mild/moderate renal insufficiency) and is in need of a major overhaul with an emphasis on the recently introduced staging of chronic kidney disease by GFR reduction. There is also variability in the recommended use of the Cockcroft-Gault equation with regard to use of estimated ideal body weight from height and build, and there has been no update to the formula to account for re-standardisation of creatinine assays.

Automatically generated eGFR using the MDRD formula more closely correlates with true GFR than an estimate based on Cockcroft-Gault (particularly in the key clinical area of GFR reduction between 15 and 60 mL/min/1.73m2) and both are better than a timed clearance. At the very least the eGFR alerts treating doctors to the possibility of reduced renal function prompting the use of other estimates if desired. In the future it is likely that eGFR will be the major basis for adjusting doses for people with reduced GFR. At present it appears reasonable and indeed preferable, in the absence of any other measure of kidney function, to use the eGFR (recognising its limitations) as a guide to prescribing particularly with non-critical dose drugs.

Timothy Mathew
Medical Director
Kidney Health Australia
Adelaide

Graham Jones
Department of Biochemistry, St Vincent's Hospital
Sydney

David Johnson Professor, Director of Nephrology
Princess Alexandra Hospital
Brisbane

Dr Randall Faull and Ms Lisa Lee, authors of the article, comment:

We are pleased there is agreement that prescribing of critical dose drugs should continue to follow published recommendations which usually use the Cockcroft-Gault equation to estimate GFR. We are however concerned about the message that body size is unimportant when considering the dosage of drugs. The automatically reported eGFR does not consider body size in its calculation, and so while it functions very well as a screening (and alert) device for renal impairment, it fails to differentiate between large and small people who will have markedly different absolute GFRs. From first principles it is the absolute GFR upon which the drug dosage should be based. The Cockcroft-Gault equation is accessible to general practitioners. Along with a calculator for ideal body weight, it is readily available on Medical Director, a computer program which is widely used by Australian general practitioners. The eGFR is an evolving tool and the MDRD equation can be adapted to consider body weight. In the future that may become the appropriate standard recommendation for calculating drug doses.