PAH) Clearances.Thesearchforalesscumbersometechniquehasledtothe Consideration of Radio-Iodinated Hippuran ( RIH ) As a Replacement of Para Aminohippuric Acid
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JOURNAL OF NUcLEAR MEDICINE 5I'4S3@46l, 1964 Correlation of Renal Clearance Techniques in Dogs: Para-Aminohippuric Acid Compared With Radio-Iodinated Hippuran' Robert H. Greenlaw, M.D. and William D. Hudgins Lexington, Kentucky There is a growing interest in the clinical application of tests of renal func tion previously used in the research laboratory. Classically, determinations of renal blood flow have been based on data derived from para-aminohippuric acid (PAH) clearances.Thesearchforalesscumbersometechniquehasledtothe consideration of radio-iodinated hippuran ( RIH ) as a replacement of para aminohippuric acid. Comparisons of RIH clearances with PAH clearances have been reported for man under conditions of continuous, simultaneous infusion of both agents ( 1), as well as under conditions of single, simultaneous injections of both agents (2). Comparisons have been made of constant-infusion PAH clearances with non simultaneous,singleinjectionRIH clearances(3).The purposeof thiscommuni cation is to report further comparisons of clearances with PAH and RIH under varying conditions in dogs. METhODS AND MATERIALS SIMULTANEOUS CLEARANCES: Fifteen adult mongrel dogs have been studied using renal function tests on 100 occasions over a period of 18 months. The status of the animals has changed from initial control condition, to left renal hypertrophy following right nephrectomy. to acute radiation exposure of the left kidney and then to post-radiation changes during the ensuing year. All function studies have been accomplished with dogs under pentobarbital anesthesia administered intravenously (30 mg/Kg). Diuresis for renal clearances has been induced by the use of 4-6 per cent solutions of urea given intravenously. PAH clearances have followed the procedure outlined by Smith (4). Briefly, a loading dose of PAH is injected (6 mg/Kg.) Following this, a continuous infusion of PAH solution (100 mg%) is given to maintain a plasma concentration of ap proximately 2 mg per cent about 4 cc/mm by drip). Twenty minutes after the ad ministration of the priming dose and the start of the sustaining infusion, the blad der is emptied, rinsed and a 20 minute clearance period started. Blood samples are ‘From the Department of Radiology, University of Kentucky Medical Center, Lexington, Kentucky. This work was carried out with the support of USPHS Grant # HE-06840-02. 453 454 GREENLAW AND HUDGINS obtained at the start, mid-point and end of each clearance period. Simultaneously with the PAH clearance period, clearance with RIH is measured. For this, the tracer is administered as a single injection, four minutes after the loading dose of PAH, based on the schedule of 0.5 sc/Kg. For RIH, the clearance period is initiated sixteen minutes after injection of tracer. Analyses of plasma and urine for PAH are according to the method of Smith (5). Samples of plasma and urine are analysed for J131 in a well-type scintilla tion counter under strict conditions of similar geometry. SEQUENTIAL CLEARANCES: In addition to simultaneous clearance studies, PAH and RIH clearances have been measured on fifty-one occasions in the same dogs, at sequential times, but during the same anesthesia. Under these conditions, the procedure for PAH clearance is identical to the above. The RIH clearance is initiated approximately 30 minutes after the discontinuation of PAH sustaining solution and an hour after the PAH loading dose. RESULTS The data comparing 100 PAH clearances with RIH clearances when the two procedures are done simultaneously are presented in Table I. In this pres entation, Status II is the situation with the animals after right nephrectomy and before irradiation of the left kidney. In general, this was a period of approxi mately twenty-four weeks Status III is the situation with the animals after ir 12 - II. - @ 10 @. 8 U U 7 6 .@. 4' . .,..@• @ 5 . 0.. • .. .....••. 0. !2 2 H SIMULTANEOUS I I I I u I I 1 I I I I 2 3 4 5 6 7 8 9 10 II 12 13 4 PAH CCIMIN/KG FIGURE I RENAL CLEARANCE TECHNIQUES IN DOGS 455 TABLE I SIMULTANEOUS CLEARANCES PAH AND RIH Animal WeightStatusStatusUrineRIHRIHKgIIIllcc/mmcc/mm/Kgcc/mm/KgPAHflowClearancePAHClearance #2B16.6X2.055.24.50.87“16.9X1.705.24.90.94“17.0X1.353.62.90.81“16.8X2.606.14.70.77“16.8X2.005.74.30.75“16.7X1.405.03.90.79“16.4X1.356.24.80.77“17.0X2.756.04.30.71#320.4X1.504.94.50.92“20.4X0.705.85.70.98“21.0X2.256.25.00.80“21.0X2.856.94.90.71“20.5X1.306.24.70.75“21.5X0.853.84.11.05•#420.8X1.104.94.10.84“20.6X1.405.25.31.02“20.2X1.705.65.81.04“20.2X2.006.05.20.87“20.4X2.256.74.80.72“20.4X2.456.85.80.85“18.2X2.307.86.60.85#517.6X1.605.14.20.82“19.5X1.505.24.40.85“20.0X1.605.54.40.80“19.7X1.424.93.80.76“19.7X1.355.94.00.69“19.8X1.003.42.80.81#617.3X1.6010.48.80.85“16.2X1.507.36.90.95“18.6X1.708.98.00.90“19.4X0.908.16.20.76“20.5X1.558.45.60.66“20.5X1.809.38.40.89“21.3X0.953.54.21.18 456 GREENLAW AND HUDGINS TABLE I—continued SIMULTANEOUS CLEARANCES PAH AND RIH A nimal WeightStatusStatusUrineRIHRIHKgIIIllcc/mmcc/mm/Kgcc/mm/KgPAHflowClearancePAHClearance #7 B 18.3 x 1.80 6.7 6.5 0.97 “ 18.9 X 1.60 7.6 6.2 0.82 22.4 X 0.90 4.0 3.4 0.85 20.8 X 1.00 4.4 3.9 0.87 208 X 2.60 6.9 5.7 0.82 20.5 X 1.00 5.3 4.1 0.77 20.8 X 1.10 5.5 4.0 0.72 #8C 19.1 x 1.10 7.3 6.2 0.85 - 20.6 x 1.30 7.8 6.8 0.87 “ 20.0 x 1.30 6.3 4.5 0.71 “ 20.5 X 2.35 6.1 5.0 0.81 20.5 X 4.02 8.4 5.9 0.69 20.6 X 2.60 5.8 4.4 0.76 21.0 X 0.90 4.2 5.0 1.18 19.8 X 2.15 5.7 5.1 0.89 #9 21.8 X 1.70 7.1 6.5 0.92 22.0 X 1.00 6.6 5.4 0.82 9.9 X 1.10 6.6 5.4 0.82 9.7 X 1.30 5.5 4.9 0.89 “ 9.9 X 1.80 4.8 4.5 0.94 “ 9.8 X 2.00 6.6 4.7 0.71 10.0 X 1.90 5.4 4.3 0.80 10.0 X 1.90 4.2 3.7 0.88 “ 10.0 X 1.70 4.7 3.8 0.81 “ 10.2 X 1.45 4.8 4.2 0.87 10.2 X 1.50 4.4 3.7 0.84 10.2 X 1.30 4.6 4.0 0.87 #11 20.6 X 1.20 7.9 6.9 0.87 19.9 X 0.90 6.1 5.5 0.90 19.8 X 0.80 6.4 5.7 0.89 22.0 X 1.60 6.4 5.7 0.89 22.3 X 1.70 7.0 5.6 0.80 22.3 X 1.20 6.8 5.5 0.81 23.5 X 0.70 5.2 4.6 0.88 RENAL CLEARANCE TECHNIQUES IN DOGS 457 TABLE I—continued SIMULTANEOUS CLEARANCES PAH AND RIH Animal WeightStatusStatusUrine—@KgIIIIIcc/mmcc/mm/Kgcc/mm/KgPAH flowClearancePAHClearance RIHRIH #12 18.0 X 0.90 8.7 6.7 0.77 17.6 X 1.20 5.4 5.6 1.04 “ 18.4 X 1.50 5.9 5.0 0.85 19.8 X 1.40 6.4 5.5 0.86 19.8 X 1.42 8.9 5.5 0.61 18.0 X 1.60 5.3 4.5 0.85 #13B 17.1 X 1.70 8.2 6.7 0.82 “ 16.8 X 2.20 7.5 6.0 0.80 17.3 X 3.95 9.6 6.9 0.72 “ 17.3 X 2.45 6.7 5.5 0.82 17.4 X 1.95 6.6 6.0 0.90 “ 17.4 X 1.25 8.0 5.9 0.74 17.9 X 2.05 7.5 6.0 0.79 17.4 X 2.65 6.2 5.1 0.81 #14 17.2 X 1.40 8.5 7.1 0.84 17.0 X 1.60 9.3 6.2 0.67 17.8 X 2.60 7.1 5.3 0.75 #15 12.8 X 1.20 6.9 6.6 0.96 12.5 X 1.60 6.1 5.8 0.95 13.0 X 2.30 5.7 5.3 0.93 13.2 X 1.50 5.4 5.2 0.96 “ 13.0 X 2.00 6.3 5.1 0.81 13.6 X 2.20 6.6 5.2 0.79 13.6 X 1.70 6.6 5.1 0.77 13.3 X 3.95 8.3 5.9 0.71 #17B 19.2 X 1.70 6.2 5.4 0.87 19.0 X 1.20 4.6 4.6 1.00 “ 17.7 X 0.90 6.4 5.6 0.88 18.9 X 1.30 5.1 4.7 0.92 18.9 X 0.95 4.8 4.0 0.83 “ 18.6 X 1.10 5.3 4.0 0.76 “ 19.3 X 1.25 3.7 3.3 0.87 458 GREENLAW AND HUDGINS radiation of the left kidney.