Assessment of glomerular filtration rate in diabetic nephropathy using the plasma clearance of ⁵¹Cr-EDTA

Abstract

Plasma clearance of ⁵¹Cr-EDTA is widely used to assess the glomerular filtration rate (GFR) in diabetic nephropathy. Originally, the ratio between the intravenously injected amount of tracer and the total area under the plasma concentration curve was used for the calculation of total ⁵¹Cr-EDTA plasma clearance (C_T). Simplified methods, using the final mono-exponential part of the plasma curve, have been suggested, e.g. four samples, taken 180 to 240 min after injection (C_IV), or using one sample taken at 240 min (C_I). Our aim was to evaluate the agreement between measurements of GFR and rate of in GFR based upon these three methods. Bland & Altman plots were used to illustrate the range of agreement. We investigated 76 insulin-dependent diabetic (IDDM) patients with microalbuminuria or diabetic nephropathy. GFR was measured after a single intravenous injection of 3.7 MBq ⁵¹Cr-EDTA by determining the radioactivity in venous blood samples taken 5, 7, 10, 15, 30, 45, 60, 90, 120, 150, 180, 200, 220,and 240 min after the injection. Rate of decline in GFR was assessed using 12 (6?17) determinations of GFR over a period of time of 8 (4?10) years. Mean (SD) GFR_T was 123 (21) ml·min^-1 compared to GFR_IV 123 (21) ml·min^-1 (NS) and GFR_I 115 (17) ml·min^-1 (p<0.00001). The mean difference (95% limits of agreement) between GFR_T and GFR_IV was + 0.6 (?16.6 to + 17.7) ml·min^-1, and between GFR_T and GFR_I + 8.0 (?6.0 to + 22.2) ml·min^-1. The difference between GFR_T and GFR_I was significantly correlated with their mean value (r=0.56, p<0.00001), indicating increasing underestimation by GFR_I with increasing GFR levels. The mean (SD) rate of decline in GFR_T was 2.3 (3.9) ml·min^-1·year^-1, compared to a mean rate of decline in GFR_IV of 2.4 (3.6) ml·min^-1·year^-1 (NS), and a mean rate of decline in GFR_I of 2.2 (3.5) ml·min^-1·year^-1 (NS). The mean difference (95% limits of agreement) between rate of decline in GFR_T and rate of decline in GFR_IV was + 0.16 (?1.59 to + 1.91) ml·min^-1·year^-1, and between rate of decline in GFR_T and rate of decline in GFR_I ?0.01 (?1.64 to + 1.61) ml·min^-1·year^-1, respectively. In conclusion, our cross-sectional study revealed a close agreement between GFR_T and GFR_IV with acceptable limits of agreement (precision), while GFR_I lacked accuracy. However, a close agreement between rate of decline in GFR_T and rate of decline in GFR_IV, and between rate of decline in GFR_T and rate of decline in GFR_I, with acceptable limits of agreement (precision), suggests that both simplified methods are applicable for long-term follow-up.