Simultaneous Measurement of Renal Clearance and Plasma Clearance of 99mTc-Labelled Diethylenetriaminepenta-Acetate, 51Cr-Labelled Ethylenediaminetetra-Acetate and Inulin in Man

1984 ◽  
Vol 66 (5) ◽  
pp. 613-619 ◽  
Author(s):  
M. Rehling ◽  
M. L. Møller ◽  
B. Thamdrup ◽  
J. O. Lund ◽  
J. Trap-Jensen

1. The present investigation was undertaken to study the kinetics of 99mTc-labelled diethylene-triaminepenta-acetate (DTPA) as compared with inulin and 51Cr-labelled ethylenediaminetetra-acetate (EDTA). 2. Twenty patients with various degrees of decreased renal function were studied. The renal clearance, plasma clearance and volume of distribution of all three tracers were measured after a simultaneous single injection. 3. The average renal clearance ratio 99mTc-DTPA to inulin was 0.97; the average renal clearance ratio 99mTc-DTPA to 51Cr-EDTA was 1.02. 4. In all patients the plasma clearance of inulin exceeded that of 99mTc-DTPA. No difference was seen between the plasma clearance of 99mTc-DTPA and 51Cr-EDTA. The plasma clearance of all three tracers overestimated the simultaneously measured renal clearance; on average this was, for 99mTc-DTPA 5.7 ml/min, for 51Cr-EDTA 6.0 ml/min and for inulin 8.1 ml/min. The plasma clearance of 99mTc-DTPA correlated well with the renal clearance of inulin, but overestimated this by 3.5 ml/min on average. 5. The volume of distribution of inulin was less than that of 99mTc-DTPA and 51Cr-EDTA. No difference was seen between the volume of distribution of 99mTc-DTPA and 51Cr-EDTA. 6. It is concluded that the difference in the kinetics of 99mTc-DTPA and 51Cr-EDTA in patients with decreased renal function was small and without clinical relevance. The two radio-actively labelled tracers can replace each other in assessment of glomerular filtration rate (GFR). The close correlation between the plasma clearance of 99mTc-DTPA after a bolus injection and the renal clearance of inulin justifies the use of the single-injection technique in assessment of GFR.

1996 ◽  
Vol 7 (1) ◽  
pp. 118-127 ◽  
Author(s):  
M Sambataro ◽  
K Thomaseth ◽  
G Pacini ◽  
C Robaudo ◽  
A Carraro ◽  
...  

It has not yet been fully clarified whether the plasma or renal clearance approach is the most reliable to investigate GFR in humans. The study presented here aimed to compare plasma decay with renal clearance of 51Cr-EDTA in 27 diabetic patients with patterns of renal function broadly dispersed in a wide range of values. Moreover, the comparison was also performed with renal clearance of nonlabeled iothalamate in a subgroup of 17 patients. A biexponential function was found to fulfill statistical and heuristic criteria for the modeling analysis of plasma 51Cr-EDTA decay with 19 samples after bolus intravenous 51Cr-EDTA injection. Individual GFR values from 51Cr-EDTA plasma clearance highly correlated with those from renal clearance (r2 = 0.977, P < 0.0001), but resulted on average about 2.5 mL.min-1.1.73 m-2 higher (66.8 +/- 6.5 mL.min-1.1.73 m-2 (mean +/- SE) versus 64.3 +/- 6.4, P < 0.02). This difference remained relatively constant from patients with normal renal function to those with impaired renal function, suggesting that the plasma clearance is slightly less accurate than renal clearance approach because of a constant extrarenal clearance rate. In the subgroup studied, a similar difference was found between GFR values from 51Cr-EDTA plasma clearance (84.7 +/- 7.3) and renal clearance of iothalamate (82.8 +/- 7.3), although not statistically significant (P = 0.4). Individual GFR values well correlated (r2 = 0.913, P < 0.0001). The precision and reproducibility of the experimental approaches were assessed by comparing three coefficients of variation: (1) CVb of the bolus injection, because of measurement errors; (2) CVc of the continuous infusion, which additionally includes errors of urine volume measurement and physiological variability in the same day; and (3) CVr of repeated measurements by using bolus injection, which also accounts for physiological variability in different days. CVc of iothalamate and 51Cr-EDTA infusions were 7.5 +/- 1.9% and 7.4 +/- 1.2% respectively. CVb and CVr of bolus injection of 51Cr-EDTA were 2.6 +/- 0.3% and 3.5 +/- 0.8% respectively. CVb and CVr of bolus injection of 51Cr-EDTA, but not CVc of iothalamate and 51Cr-EDTA infusions were twofold to tenfold lower than the percent yearly change reported in IDDM and NIDDM patients. More particularly, CVr was significantly less than CVc. In order to make the test less cumbersome, a reduced sampling schedule with seven samples was designed and validated. GFR measured with seven samples was 66.1 +/- 6.4 (P = 0.1 when compared with the full 19-sample schedule) with a CVb of 3.5 +/- 0.5%. This seven-sample protocol was not different from that obtained with the previously described simplified method of Brøchner-Mortensen (63.9 +/- 6.8, P = 0.16), yet yielding a statistically more accurate estimate (coefficient of variation for Brøchner-Mortensen method = 12.1 +/- 2.9, P = 0.004). Moreover, only bolus injection, along with modeling analysis of plasma clearance rate, allows the accurate measurement of the extracellular fluid volume, an important parameter in diabetic patients. It was concluded that the reduced seven-plasma sample protocol is able to detect as small as 4 to 5% changes per year in a single patient. Moreover, it provides precise and accurate estimate of GFR in diabetic patients with hyperfiltration, who are postulated to be at higher risk to develop renal damage.


1982 ◽  
Vol 63 (1) ◽  
pp. 47-51 ◽  
Author(s):  
J. A. C. Prenen ◽  
P. Boer ◽  
E. J. Dorhout Mees ◽  
H. J. Endeman ◽  
S. M. Spoor ◽  
...  

1. The renal clearance of [14C]oxalate was assessed by the constant-infusion technique and single-injection technique (plasma sampling only: one-compartment and two-compartment model; plasma and urine sampling). Healthy volunteers and patients with renal stones were studied. 2. Results with the constant-infusion techniques (with and without urine sampling) were not significantly different from each other. 3. The renal clearance of [14C]oxalate measured with the single-injection technique as compared with the constant-infusion technique was overestimated in the single-injection one-compartment model (52%) as well as in the two-compartment model (30%). 4. The calculated level of plasma oxalate in the healthy volunteers ranged from 1·04 to 1·78 μmol/l (mean 1·39). 5. The biological half-life of [14C]oxalate, estimated by the cumulative excretion of 14C in urine after equilibrium had been established, was 128 min (range: 113–142). 6. The oxalate/creatinine clearance ratio in the healthy volunteers ranged from 1·73 to 2·22 (mean 2·01).


1993 ◽  
Vol 11 (12) ◽  
pp. 2314-2323 ◽  
Author(s):  
D R Newell ◽  
A D Pearson ◽  
K Balmanno ◽  
L Price ◽  
R A Wyllie ◽  
...  

PURPOSE The aim of this study was to define the pharmacokinetics of carboplatin in children and use the data to develop a pediatric dose formula. It was anticipated that renal function would be a major determinant of carboplatin disposition and the relationship between carboplatin clearance and glomerular filtration rate (GFR) was examined in detail. PATIENTS AND METHODS Plasma carboplatin pharmacokinetics were measured as ultrafiltrable platinum in 22 patients (5 to 63 kg) following 200 to 1,000 mg/m2 of carboplatin. GFR was measured by the plasma clearance of chromium 51-edathamil (51Cr-EDTA). RESULTS Carboplatin pharmacokinetics in children were best described in most patients (16 of 22) by a two-compartment model. The dose-normalized area under the plasma carboplatin concentration versus time curve (AUC) ranged from 3.1 to 9.6 mg/mL.min/400 mg/m2 and there was only a weak linear relationship between carboplatin dose and AUC (R2 = .31). There was a significant relationship between absolute carboplatin and 51Cr-EDTA clearances (R2 = .56), but the relationship was weaker (R2 = .28) when both clearances were normalized for body surface area. Carboplatin plasma clearance was predicted by the equation: clearance = GFR (mL/min) + 0.36 x body weight (BW; kg), and a modified form of the adult carboplatin dose formula is proposed: dose (mg) = target AUC x (GFR [mL/min] + [0.36 x BW(kg)]). Two further equations were developed that use the 51Cr-EDTA half-life (t1/2) to calculate the GFR and these may reduce errors resulting from inaccurate measurement of the volume of distribution for 51Cr-EDTA. In patients treated with single-agent carboplatin or carboplatin plus vincristine, there was a significant sigmoidal relationship between AUC and thrombocytopenia (R2 = .56). CONCLUSION GFR-based carboplatin dosing in children should be feasible and will be evaluated prospectively.


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