ASSESSMENT OF GLOMERULAR-FILTRATION RATE IN DIABETIC NEPHROPATHY USING THE PLASMA-CLEARANCE OF CR-51-EDTA

Plasma clearance of Cr-51-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 Cr-51-EDTA plasma clearance (CT) Simplified methods, using the f inal mono-exponential part of the plasma curve, have been suggested, e .g. four samples, taken 180 to 240 min after injection (C-IV), or usin g one sample taken at 240 min (C-I). Our aim was to evaluate the agree ment between measurements of GFR and rate of decline in GFR based upon these three methods. Bland & Altman plots were used to illustrate the range of agreement. We investigated 76 insulin-dependent diabetic (ID DM) patients with microalbuminuria or diabetic nephropathy. GFR was me asured after a single intravenous injection of 3.7 MBq Cr-51-EDTA by d etermining the radioactivity in venous blood samples taken 5, 7, 10, 1 5, 30, 45, 60, 90, 120, 150, 180, 200, 220, and 240 min after the inje ction. Rate of decline in GFR was assessed using 12 (6 - 17) determina tions 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 GFRT 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.mi n(-1). The difference between GFR(T) and GFR(I) was significantly corr elated with their mean value (r = 0.56, p < 0.00001), indicating incre asing 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), compa red 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).ye ar(-1), respectively. In conclusion, our cross-sectional study reveale d a close agreement between GFR(T) and GFR(IV) with acceptable limits of agreement (precision), while GFR(I) lacked accuracy. However, a clo se 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.