Accurate and precise plasma clearance measurement using four 99mTc-DTPA plasma samples over 4 h

Abstract

Objectives: Glomerular filtration rate can be measured as the plasma clearance (CL) of a glomerular filtration rate marker despite body fluid disturbances using numerous, prolonged time samples. We desire a simplified technique without compromised accuracy and precision.

Materials and methods: We compared CL values derived from two plasma concentration curve area methods - (a) biexponential fitting [CL (E2)] and (b) Tikhonov adaptively regularized gamma variate fitting [CL (Tk-GV)] - for 4 versus 8 h time samplings from 412 Tc-DTPA studies in 142 patients, mostly paediatric patients, with suspected fluid disturbances.

Results: CL (Tk-GV) from four samples/4 h and from nine samples/8 h, both accurately and precisely agreed with the standard, which was taken to be nine samples/8 h CL from (noncompartmental) numerical integration [CL (NI)]. The E2 method, four samples/4 h, and nine samples/8 h median CL values significantly overestimated the CL (NI) values by 4.9 and 3.8%, respectively.

Conclusion: Compared with the standard, CL (E2) from four samples/4 h and from nine samples/8 h proved to be the most inaccurate and imprecise method examined, and can be replaced by better methods for calculating CL. The CL (Tk-GV) can be used to reduce sampling time in half from 8 to 4 h and from nine to four samples for a precise and accurate, yet more easily tolerated and simplified test.

Fig. 1

Histograms of (a) the differences between CL values obtained using the E2 (8 h, nine samples) method (CL_E2all) and reference clearance values (CL_ref), and (b) difference between CL values obtained using the Tk-GV (8 h, nine samples) method (CL_Tk-GVall) and reference clearance values (CL_ref) as a percentage of reference clearance values. The vertical red lines represent the median values. The black solid lines represent zero difference and the black dashed lines represent the −10% and 10% differences limits for outliers between the estimated and the reference values. CI, confidence interval; CL, plasma clearance; IQR, interquartile range.

Fig. 2

CL values obtained using (a) the E2 (4 h, four samples) method (CL_E2few) and (b) the Tk-GV (4 h, four samples) method (CL_Tk-GVfew) as a function of CL values obtained using the reference method (CL_ref). CI, confident interval; CL, plasma clearance.

Fig. 3

Histograms (left side) and Bland–Altman plots (right side) of (a) the differences between CL values obtained using the E2 (4 h, four samples) method (CL_E2few) and the reference clearance values (CL_ref, 8 h, nine samples) and (b) the difference between CL values obtained using the Tk-GV (4 h, four samples) method (CL_Tk-GVfew) and reference clearance values (CL_ref) as a percentage of reference clearance values. The dashed red lines represent the median values of the estimates. The black solid lines represent zero difference between methods and the black dashed lines represent the −10% and 10% difference limits for outliers between the estimated and reference values. CI, confidence interval; CL, plasma clearance; IQR, interquartile range.