Appendix IX. Estimation of Glomerular Filtration Rate

Several guideline statements refer to glomerular filtration rates (GFR) below which certain monitoring strategies or therapies should be instituted. The inulin clearance is considered to be the most accurate measure of the GFR. However, it is a laborious and rather expensive measurement. We describe here recommended methods for determining GFR that are more useful under clinical conditions.

GFR can be estimated from the serum creatinine concentration and other factors, or determined more precisely using either timed urine collections or radioisotope elimination methods.265-267 For the purposes recommended in these guidelines, the estimated GFR will usually be sufficient to provide a useful "ballpark" value for the GFR (ie, < 25 mL/min). Direct urinary clearance measurements will be more useful in determining the degree of renal dysfunction at lower levels of clearance, when the need for renal replacement therapy is entertained.

The most widely used method for estimating GFR is the Cockcroft-Gault equation.266 This equation considers the effects of age, sex, and body weight on creatinine generation (ie, on average, increased age, female sex, and decreased weight associated with reduced creatinine generation; Guideline 5), thereby adjusting serum creatinine values to more accurately reflect creatinine clearance.

More recently, an equation was derived from data obtained from the MDRD study, GFR measured by iothalamate clearances as the standard of measurement.267 In addition to incorporating the influence of age and gender, the effects of race, and three (rather than one) biochemical measures are included:

Timed urine collections are considered by most investigators to be valuable, albeit flawed measurements of GFR. Creatinine clearance is the value most frequently employed. As the GFR falls, however, the creatinine clearance progressively overestimates GFR, to a degree that may approach twice the true GFR value (< 15 to 20 mL/min). At these levels of renal function, a more valid approximation of the GFR can be obtained using an average of the creatinine and urea clearances. Others have advocated the use of a creatinine clearance after administration of cimetidine, a drug known to block creatinine secretion. The accuracy of the timed urine collection is dependent on the integrity of the collection (among other factors). The creatinine index (Guideline 5) is often used to confirm whether a collection is appropriate, insufficient, or in excess. Radioisotope elimination methods (eg, ethylenediaminetetraaceticacid [EDTA], iothalamate) can be more accurate, but are limited by time constraints and expense.