Assessment of iothalamate plasma clearance: duration of study affects quality of GFR

Abstract

Background and objectives: Measurement of GFR is important for the management of chronic kidney disease (CKD). Although bolus administration of radiocontrast agents is commonly used to measure GFR, the optimal duration of sampling to assess their plasma clearance is unknown. The purpose of this study was to evaluate whether the duration of plasma sampling influences precision and estimation of GFR.

Design, setting, participants, & measurements: GFR was measured by sampling plasma 12 times over 5 h in 56 patients with CKD (mean age 64 yr, 98% men, 79% Caucasian, 34% diabetics, estimated GFR 31.8 +/- 14.2 ml/min/1.73 m(2)). In a subset of 12 patients we measured GFR by sampling plasma 17 times over 10 h.

Results: Short sampling intervals considerably overestimated GFR measured using total plasma iothalamate clearance, especially in larger patients. In the higher estimated GFR group (>30 ml/min/1.73 m(2)), the 5-h GFR was 17% higher and 2-h GFR 54% higher compared with the 10-h GFR, which averaged 40.3 ml/min/1.73 m(2). In the lower estimated GFR group (<30 ml/min/1.73 m(2)), the 5-h GFR was 36% higher and 2-h GFR 126% higher compared with the 10-h GFR, which averaged 22.2 ml/min/1.73 m(2). Short sampling duration also reduced the precision of the estimated GFR from 1.67% for 10-h GFR, to 3.48% for 5-h GFR, and to 7.07% for 2-h GFR.

Conclusions: GFR measured over a longer duration with multiple plasma samples spanning the distribution and elimination phases may improve precision and provide a better measure of renal function.

Figure 1.

Pharmacokinetic profile of plasma iothalamate concentration versus time curves in 12 patients with chronic kidney disease (CKD) who had measurements over 10 h. An exponential decline is visible although the data are plotted on a logarithmic ordinate. Thus, a two-compartment pharmacokinetic model was fitted. Symbols are the actual plasma iothalamate concentration in each patient, whereas the lines are the model fitted curves.

Figure 2.

Body surface area-corrected GFR as measured by plasma iothalamate clearance are overestimated if shorter sampling times are used. The individual changes in plasma iothalamate clearance are denoted by arrows. As the sampling time shortens, the plasma iothalamate clearance is overestimated. Some individuals have large changes in measured GFR.

Figure 3.

The overestimation in GFR plateaus at about 6 to 7 h in people with estimated GFR (eGFR) of 30 ml/min/1.73 m². However, this plateau may not occur until a later time point in those with lower kidney function. The solid lines are modeled relationships between iothalamate clearances and sampling times in those with lower eGFR (<30 ml/min/1.73 m²) whereas the dashed lines are relationships in those with higher eGFR (>30 ml/min/1.73 m²). Open triangles are measured plasma iothalamate clearances in those with higher eGFR and circles in those with lower eGFR.

Figure 4.

Measured plasma iothalamate concentrations versus time are shown on a logarithmic ordinate in one patient. The lines represent modeled curves when various durations of sampling are considered. When GFR was analyzed over 10 h (full data) the topmost curve was obtained, which yielded a GFR of 37 ml/min. The bottom solid line shows a modeled curve when only 2 h of data were considered. GFR using the 2-h data were 72 ml/min. Overestimation of the terminal elimination constant by short studies is why GFR appear to be overestimated with short durations of measurement.