CLEARANCE OF IOHEXOL, CR-51-EDTA AND ENDOGENOUS CREATININE FOR DETERMINATION OF GLOMERULAR-FILTRATION RATE IN PIGS WITH REDUCED RENAL-FUNCTION - A COMPARISON BETWEEN DIFFERENT CLEARANCE TECHNIQUES

In order to simplify and/or improve determination of glomerular filtra tion rate (GFR) the clearances of iohexol, Cr-51-EDTA and endogenous c reatinine were simultaneously determined with different techniques in 21 anesthetized landrace pigs. Their GFR had been reduced to about 1/3 or less of normal GFR. After an intravenous bolus of the GFR markers, their plasma concentration curves were followed for 6 hours with 16 p lasma samples. A bladder catheter collected urine during six 60-min pe riods. The plasma clearance was calculated by dividing ''dose of marke r'' with ''area under the plasma concentration curve'' (AUC) from the time of injection to infinity using a one-(Cl-provisional) and a three -compartment (ClAUC-3comp) model. The renal clearance of iohexol and C r-51-EDTA was calculated by dividing the amount of marker excreted in the urine in a period by AUC in the same period. The AUC was for iohex ol and Cr-51-EDTA determined by integrating the total area in the peri od (Cl-ren adv) - our reference method representing the ''true'' GFR a nd for creatinine determined by using the arithmetic mean of the plasm a concentration of the marker at the start and at the end of the urine collection period (Cl-ren simple). Renal clearance of creatinine was significantly lower than renal clearance of iohexol (p=0.0019) and Cr- 51-EDTA (p=0.0001). There were no significant differences between the renal clearances (Cl-ren adv) of iohexol and Cr-51-EDTA or between the ir plasma clearances (ClAUC-3comp). For iohexol the median overestimat ion of the ''true'' GFR with Cl-provisional was higher when ''early'' plasma samples (30-120 min) were used (4.5 ml min(-1) 10 kg(-1)) than when late samples (180-360 min) were used (1.9 ml min(-1) 10 kg(-1)). Subtraction of the median extrarenal clearance (known from a study of nephrectomized pigs) from the plasma clearances (ClAUC-3comp) of iohex ol and Cr-51-EDTA in pigs with reduced renal function decreased the me dian overestimation of the ''true'' GFR from 1.9 to 1.0 ml min(-1) 10 kg(-1) with iohexol and from 1.7 to 0.9 ml min(-1) 10 kg(-1) with Cr-5 1-EDTA. The plasma clearance technique may be improved in pigs with re duced GFR by (i) including a ''late'' plasma sample in three- and one- compartment models, which tends to increase the AUC; (ii) introducing a correction formula by normalizing the GFR values of the one-compartm ent model to those of the three-compartment model, thereby compensatin g for the rapid early changes in plasma concentration of marker after the bolus injection of the marker; or (iii) subtracting a median (or m ean) extrarenal clearance of the marker in pigs from the plasma cleara nce [according to (i) or (ii)]. The plasma clearance one-compartment t echnique may be improved in pigs with various levels of GFR values by normalizing the plasma clearance values to the renal clearance values, thereby compensating for both the early changes in plasma concentrati on of marker and the extrarenal clearance of marker.