Article Figures & Data
Figures
- 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.
Tables
Characteristic Result Number of subjects 56 Age (yr) 64.3 ± 10.7 Men 55 (98%) Height (in) 68.3 ± 3.5 Weight (kg) 99.3 ± 24.2 Hip/waist ratio 1.01 ± 0.08 Body mass index (kg/m2) 32.8 ± 6.9 Body surface area (m2) 2.12 ± 0.27 Race White 44 (79%) Black 10 (18%) American Indian 2 (4%) Etiology of CKDb diabetes 19 (34%) hypertension 20 (36%) GN 9 (16%) other 8 (14%) Hemoglobin (g/dl) 12.3 ± 1.6 Albumin (g/dl) 4.1 ± 0.3 Plasma creatinine (mg/dl) 2.6 ± 1.2 Blood urea nitrogen (mg/dl) 44.7 ± 25.5 Estimated GFR (ml/min/1.73 m2) 31.8 ± 14.2 stage 2 3 (5%) stage 3 24 (43%) stage 4 25 (45%) stage 5 4 (7%) Median urine protein/creatinine (g/g) (interquartile range) 0.40 (0.11–1.36) Pharmacokinetic Parameter Median Q1 Q3 Plasma iothalamate clearance (ml/min) 47.8 33.9 65.6 Plasma iothalamate clearance (ml/min/1.73m2) 37.7 30.1 50.6 Volume of distribution central (ml) 4797 2275 6266 Volume of distribution (ml/kg) 50.1 20.0 67.4 Volume of distribution, steady state (ml) 15908 13822 18827 Volume of distribution, steady state (ml/kg) 172.4 147.1 190.6 Elimination half-life (min) 66 24 115 Area under curve (μg × min/ml) 62856 45847 89286 Fast component intercept A (μg/ml) 452 320 1207 half-life ln(2)/α (min) 4.83 2.39 7.18 area A/α (μg·min/ml) 5335 2843 3624 Slow component intercept B (μg/ml) 161 136 183 half-life ln(2)/β (min) 271 199 336 area B/β (μg·min/ml) 57615 40924 81973 ↵a Q1, first quartile; Q3, third quartile.
Sampling Duration Mean GFR (ml/min/1.73 m2) 95% CIb Ratio Compared to 5-h GFR 95% CI of Ratio P eGFR stratum >30 ml/min/1.73m2 5 h 49.3 44.4 to 54.8 4 h 52.5 47.2 to 58.3 1.06 0.99 to 1.14 0.084 3 h 57.2 51.5 to 63.5 1.16 1.08 to 1.25 <0.001 2.5 h 60.4 54.4 to 67.2 1.23 1.14 to 1.32 <0.001 2 h 66.1 59.5 to 73.4 1.34 1.25 to 1.44 <0.001 eGFR stratum <30 ml/min/1.73m2 5 h 29.1 26.3 to 32.2 4 h 32.0 28.9 to 35.4 1.10 1.03 to 1.18 0.007 3 h 34.5 31.2 to 38.2 1.19 1.11 to 1.27 <0.001 2.5 h 38.2 34.6 to 42.3 1.31 1.23 to 1.41 <0.001 2 h 44.4 40.1 to 49.1 1.53 1.42 to 1.63 <0.001 Sampling Duration Mean GFR (ml/min/1.73 m2) 95% CI Ratio Compared to 10-h GFR 95% CI of Ratio P eGFR stratum >30 ml/min/1.73m2 10 h 40.3 33.2 to 48.9 9 h 41.2 34.1 to 49.8 1.02 0.92 to 1.14 >0.2 8 h 42.1 34.8 to 50.9 1.04 0.94 to 1.16 >0.2 7 h 43.7 36.1 to 52.8 1.08 0.97 to 1.21 0.15 6 h 45.2 37.4 to 54.7 1.12 1.01 to 1.25 0.037 5 h 47.2 39.0 to 57.1 1.17 1.05 to 1.31 0.004 4 h 49.3 40.7 to 59.6 1.22 1.10 to 1.36 <0.001 3 h 53.1 43.8 to 64.4 1.32 1.18 to 1.48 <0.001 2.5 h 56.7 46.9 to 68.6 1.41 1.26 to 1.57 <0.001 2 h 62.3 51.5 to 75.3 1.54 1.39 to 1.72 <0.001 eGFR stratum <30 ml/min/1.73m2 10 h 22.2 18.4 to 26.9 9 h 23.6 19.5 to 28.6 1.06 0.96 to 1.18 >0.2 8 h 24.8 20.5 to 30.0 1.12 1.01 to 1.24 0.037 7 h 25.9 21.4 to 31.3 1.16 1.05 to 1.29 0.004 6 h 27.5 22.7 to 33.3 1.24 1.12 to 1.37 <0.001 5 h 30.3 25.0 to 36.6 1.36 1.23 to 1.51 <0.001 4 h 33.4 27.6 to 40.4 1.50 1.36 to 1.67 <0.001 3 h 39.4 32.5 to 47.8 1.77 1.59 to 1.98 <0.001 2.5 h 44.6 36.9 to 54.0 2.01 1.81 to 2.23 <0.001 2 h 50.2 41.5 to 60.7 2.26 2.04 to 2.51 <0.001 ↵a Mean GFR calculated using a nominal mixed model with maximal likelihood estimates.
Parameter Coefficient 95% CI P Fixed effects constant (ml/min/1.73 m2) 58.6 46.4 to 70.8 <0.001 sampling time (h) −11.7 −14.2 to −9.2 <0.001 sampling time2 (h2) 0.676 0.48 to 0.87 <0.001 eGFR (ml/min/1.73 m2) 0.369 −0.01 to 0.75 0.057 eGFR × sampling time 0.119 0.04 to 0.20 0.003 eGFR × sampling time2 −0.007 −0.013 to −0.001 0.021 Random effects intercept SD 7.66 5.01 to 11.72 sampling time SD 0.624 0.380 to 1.027 correlation (time, intercept) −0.85 −0.96 to −0.53 residual SD 2.56 2.22 to 2.96 ↵a Random coefficient model with maximal likelihood estimates.
Sampling Duration Mean AUC (μg · min/ml) 95% CI Ratio compared to 10-h AUC 95% CI of Ratio P eGFR stratum >30 ml/min/1.73m2 10 h 65,427 51,731 to 82,749 9 h 63,968 50,707 to 80,697 0.98 0.88 to 1.09 >0.2 8 h 62,603 49,625 to 78,975 0.96 0.86 to 1.07 >0.2 7 h 60,365 47,851 to 76,151 0.92 0.83 to 1.03 0.15 6 h 58,271 46,191 to 73,510 0.89 0.80 to 0.99 0.037 5 h 55,796 44,229 to 70,388 0.85 0.76 to 0.95 0.004 4 h 53,466 42,382 to 67,449 0.82 073 to 0.91 <0.001 3 h 49,628 39,240 to 62,768 0.76 0.68 to 0.85 <0.001 2.5 h 46,464 36,831 to 58,615 0.71 0.64 to 0.79 <0.001 2 h 42,330 33,555 to 53,400 0.65 0.58 to 0.72 <0.001 eGFR stratum <30 ml/min/1.73m2 10 h 105,432 83,576 to 133,005 9 h 99,198 78,633 to 125,140 0.94 0.85 to 1.04 >0.2 8 h 94,490 74,901 to 119,201 0.90 0.81 to 0.99 0.037 7 h 90,584 71,805 to 114,273 0.86 0.77 to 0.95 0.004 6 h 85,141 67,491 to 107,407 0.81 0.73 to 0.90 <0.001 5 h 77,359 61,322 to 97,590 0.73 0.66 to 0.81 <0.001 4 h 70,104 55,571 to 88,438 0.66 0.60 to 0.74 <0.001 3 h 59,402 46,968 to 75,126 0.56 0.51 to 0.63 <0.001 2.5 h 52,466 41,589 to 66,187 0.50 0.45 to 0.55 <0.001 2 h 46,656 36,984 to 58,857 0.44 0.40 to 0.49 <0.001 ↵a AUC calculated using a nominal mixed model with maximal likelihood estimates.
Sampling Duration Mean GFR CV (%) 95% CI Difference from 10-h GFR 95% CI of Difference P 10 h 1.67 1.38 to 2.01 9 h 1.81 1.50 to 2.18 1.09 0.93 to 1.27 >0.2 8 h 2.06 1.71 to 2.48 1.24 1.06 to 1.44 0.007 7 h 2.38 1.98 to 2.87 1.43 1.23 to 1.67 <0.001 6 h 2.85 2.37 to 3.43 1.71 1.47 to 1.99 <0.001 5 h 3.48 2.89 to 4.19 2.09 1.79 to 2.44 <0.001 4 h 4.31 3.58 to 5.19 2.59 2.22 to 3.02 <0.001 3 h 4.86 4.01 to 5.89 2.91 2.48 to 3.42 <0.001 2.5 h 6.11 5.08 to 7.36 3.67 3.15 to 4.28 <0.001 2 h 7.07 5.87 to 8.51 4.24 3.63 to 4.95 <0.001 ↵a Mean GFR coefficient of variation (CV) calculated using a nominal mixed model with log-transformed CV using maximal likelihood estimates.
In this issue
