Conventional measurements of GFR using ⁵¹Cr-EDTA overestimate true renal clearance by 10 percent

Abstract.

It is widely believed that measurement of the area under the plasma clearance curve (AUC) following a single intravenous injection of chromium-51 labelled ethylene diamine tetra-acetic acid (⁵¹Cr-EDTA) is a gold standard method for determining glomerular filtration rate (GFR). However, there are reports that ⁵¹Cr-EDTA may have a significant extrarenal clearance. The aim of this study was to identify the non-renal component of ⁵¹Cr-EDTA plasma clearance contributing to the AUC measurement of GFR. Seventy healthy postmenopausal women (mean age 60 years, range 45–79 years) were injected with 3 MBq ⁵¹Cr-EDTA and 0.25 MBq iodine-125 labelled human serum albumin and 11 blood samples taken between 0 and 4 h through an indwelling venous cannula. For the first 21 subjects, two complete urine collections were made 0–2 h and 2–4 h after injection, and for the final 49 patients, four 1-h urine collections were made. The mean ⁵¹Cr-EDTA total plasma clearance was 84 ml/min (range 50–132 ml/min). The mean ratio (SEM) of urine to total clearance determined from the cumulative 1-, 2-, 3- and 4-h data was 0.903 (0.018), 0.891 (0.013), 0.898 (0.011) and 0.899 (0.010) respectively and remained constant despite the mean urine concentration decreasing from 122% to 15%/litre during this period. A least squares fit to data from the 238 individual urine collections was used to determine the fraction of the total plasma clearance attributable to renal clearance, α₀, and the residual urine volume, ΔV. The results were α₀=0.910 (95% CI: 0.889–0.932) and ΔV=14 ml (95% CI: –4 to +34 ml). The overestimation of the true renal clearance of ⁵¹Cr-EDTA by the AUC method is believed to be due to the failure of the plasma clearance curve to reach the true terminal exponential by 2 h after injection as usually assumed. As a result, conventional measurements of GFR using ⁵¹Cr-EDTA overestimate the true renal clearance of tracer by approximately 10%.