RADIONUCLIDES IN RENAL TRANSPLANTATION G. Hör,H. W. Pabst,K. J. Pfeifer,P. Heidenreich,H. Langhammer,and H. G. Heinze Nuk'earmedizinische Klinik und Poliklinik der Technischen Universität and Klinik und Poliklinik fürRadiologie der UniversitätMünchen,Munich, Germany In the terminal stages of renal failure, renal trans plantation has become an effective means of treat TABLE1. RADIONUCLIDESIN RENAL ment (1,2) . Although survival rates have improved TRANSPLANTATION since the availability of adequate immunotherapy, Procedureo-1'@l-hippuricRadiopharmaceutical present means of diagnosing the various forms of acid Isotoperenography Tubular renal complications leave much to be desired. Effective renal function Since 1966 180 kidney transplantations have been plasma flow @ lismIn ‘@Yb. Isotope renography Glomerular performed at the university clinics in Munich (2). EDTA, -DTPA Renal clearance function Encouraged by communications of other authors ‘°‘Hg-mersalyl Scanning Localization (3—9)we have begun to use procedures involving ra “@Hg-chlormerodrin Scanning Localization ‘311-flbrinogen Scanning Localization dioisotopes, and results were compared with nephro “Xeclearance Renal blood logical testing procedures ( 10—iS). flow vsmTcO@ Clinical diagnosis was based on the clinical course, Scintillation camera Vascular perfusion palpation of the transplant, urine volume, serum creatinine, creatinine clearance, sodium excretion, urinary osmolarity, and biopsy. Radiological procedures were usually confined to into the arterial branch of the exteriorized kidney abdominal x-ray when kidney size was of interest. which was mounted to the forearm of the patient. Drip infusion urography was used when extravasa Renal cortical blood flow (RCBF) was deter tion of urine (urinary fistula) was suspected, and mined by externally monitoring the 133Xe washout arteriography was performed to exclude arterial from the exteriorized kidney. Graphical analysis of stenosis or thrombosis. the radioxenon disappearance curve was performed using rapid component I , its half-time, and lambda METHODS as the partition coefficient of radioxenon between Several radionuclide procedures were chosen for kidney blood and parenchyma, dependent on the the evaluation of function and morphological dis hematocrit. RCBF was related to kidney weight. orders of the renal transplants. These are summarized Renal scanning. Renal scanning was performed in in Table 1. 62 patients using 203Hg-mersalyl, ‘97Hg-chlormero Renography. One hundred fifty-three followup drin, and lI3mIn..Fe..EDTA, with a Picker Magna studies were carried out with 1311-o-hippuric acid scanner 500. (OIH) to estimate glomerular and tubular function. Sequential scintigraphy. Sequential scintigraphy (Since OIH measures effective renal plasma flow, was carried out in another I 6 patients using 250 @Ci it is listed as tubular function in the tables and re of 169Yb-EDTA and a Picker Anger scintillation ferred to as such in the test that follows.) Thirty-two camera. patients were additionally investigated using fl3mIn@ Renal clearance studies. Renal clearance studies Fe-EDTA (In) to study glomerular function alone. were performed in 30 followup examinations. One 133Xe clearance. During preservation of an ex tracorporeal cadaver kidney transplant in a perfusion Received Jan. 10, 1972; original accepted May I 1, 1972. chamber (16), 200—500 @Ciof radioxenon dissolved For reprints contact: 0. Hör,Nuklearmed. Klin. d. TU, in 3—5ml of sterile saline were injected selectively Ismaningerstrasse, 8 München80, Germany. Volume 13, Number 11 795 H@R, PABST, PFEIFER, HEIDENREICH, LANGHAMMER, AND HEINZE the decline of radioactivity in the whole body, with the exception of kidney and bladder which were shielded by lead. Several plasma samples were drawn, and radioactivity (C1)Ifl$ma)was determined in the well counter. Clearance (Cl) was calculated @ according to the formula of Oberhausen (18) sepa A. L.ø rately for OIH and 169Yb-EDTA: A Cf=@@dm/dt C p1a@ma RESULTS In acute rejection crises the following criteria were found (Fig. 1): 1. OIH accumulation (lack of excretory segment) or prolonged secretory maximum (Tmax), fall in un nary osmolanity, lack of bladder activity, and mar @ —a *1 ginal filling defects in the scan (Fig. 1B). 2. There is a decrease in endogenous C-CR. Cor relation between parameters of radionuclide renog raphy and the level of serum creatinine is presented in Table 2. There is a positive correlation between serum creatinine and the elimination index of the OIH and In-Fe-EDTA renograms, and a negative correlation between serum creatinine and accumula tion index of renography. 3. Differentbehaviorbetweentubularand gb merular function was found in acute tubular necrosis of transplanted cadaver kidneys that were subject to prolonged ischemia time before transplantation. B F1G. 1. (A)OlH renogramin acuterejection:OIH accumula tion. (B) Photoscan (‘°@Hg.mersalyl)in anuric rejection crisis (same patient): radioactivity in periphery (cortical area) reduced, no blad. 24270 20370 25370 der activity. hundred fifty microcunies of OIH were given intra venously, followed by 250 @Ciof ‘69Yb-EDTA20 mm later for combined investigation of renal plasma flow (RPF), and glomerular filtration (GFR). The filtration fraction (GFR/RPF) was estimated (17). Renal clearance was calculated according to the . FIG. 2. Followup study with OIH- and “mln.EDTA renography whole-body pnnciple (18) by externally monitoring in kidneytransplant:rejectioncrisison March20, 1970. TABLE2. CORRELATiONBETWEENSERUM-CREATININE(MG%) AND ISOTOPERENOGRAPHY (KIDNEYTRANSPLANTS) Tubular functionGlomerular function“3mIn.EDTA max.Renography Accum. ratio‘@l.o.HippumnEIim. ratio Secret. max. Accum. ratio Elim. ratio Filtrat. n 41 35 25 38 33 38 r —0.662 +0J63 +0.595 —0.502 +0.530 +0.572 0.11 0.037 0.267 0.164 0.0678 0.950 p <0.001 <0.001 <0.01 <0.01 <0.01 <0.01 Accumulation ratio (1 .5/0.5 mm-activity). Elimination ratio (20.0/0.5 mm-activity). 796 JOURNAL OF NUCLEAR MEDICINE @ :@*@ RADIONUCLIDESIN RENALTRANSPLANTATION TABLE3. RENOGRAPHICFOLLOWUPSTUDIES OF CADAVERKIDNEYTRANSPLANTSWITH TUBULAR NECROSIS Total ischaemiarenogram(mm)(daystimeNormalization of after) 239 19 203 16 159 5 155 8 115 5 109 3 As an example of differences in glomerular and tubular function in acute rejection crises see Fig. 2, second panel. Note the continuous OIH accumula tion without excretion but excellent excretion of llsmln..FeEDTA The OIH renogram became nor mal on March 25, 1970. 4. In acute tubular necrosis delayed transit time of OIH seems to depend on the duration of ischemia FIG.3. Colorscan(“mln-EDTA)inkidneytransplantwithdou time of the cadaver kidney before transplantation bled renal artery: obstruction of upper branch. Note retention of (Table 3). radioactivity in area of renal pelvis. 5. The ll3mInEDTA wasfoundto be rapidlyex @ creted by normally functioning transplant kidneys so - that this radiopharmaceutical is more suitable for tests by the scintillation camera (Fig. 3). Arterial @ ,z@: thrombosis or complete occlusion results in total loss @, ,@ of accumulation of radioactivity. 6. Rectilinear scans using 203Hg-mersalyl or 197Hg chbormerodninwere characterized by filling defects in the center, in the upper, or in the lower pole of the rejected kidney as has been reported by us pre 9-11' 6-8' 2-i' viously (11). 7. Sequentialscanningafter injection of 169Yb EDTA and/or OIH presented no characteristic pat 62 mI/mm tern in rejection of the kidney transplant and was of no predictive value (Fig. 4). 8. Renalclearancestudies,however,gaveaddi kjdney tional information concerning the functional state of the rejected transplant (Fig. 4) . Simultaneous de termination of the clearances of OIH and 169Yb EDTA showed disproportionate reduction of RPF compared with GFR, so that ifitration in rejection crises was elevated (Fig. 5). 9. In some cases determination of the washout of 133Xein the kidney before transplantation, while pre FIG.4. Serialscintiphotography(sequentialscintigraphy)and served in a perfusion chamber, proved to be of OIH-single shot clearance in acute rejection. prognosticvalue when RCBF has been found normal (Fig. 6). From our folbowup studies we conclude that pa rameters of OIH as well as of the fl3mIn@Fe@EDTA DISCUSSION renogram are generally in accordance with the level Radionuclide renography is now an acknowledged of serum creatinine. and easily performed diagnostic tool for elucidating Collins, et al (3), Sharpe, et al (8) , and Staab, complications following renal transplantation. et al (9) have also reported on the prognostic value Volume 13, Number 11 797 @ p@, A H@R, PABST, PFEIFER, HEIDENREICH, LANGHAMMER, AND HEINZE - 133 x.@ Oecrance of a transplanted Clearance kidney in the chamber 01 Lavender @ 1@@@. ,,@/g. IRc8F@ @ 1@ “.“.PlOp) @ A . @v 10 A@02, : 131 J-Hippuran-Clearance 50 100 150 200 250 300 350 ml/'viln F1G.5. Comparativeglomerularand tubularclearancein transplanted kidneys. of radionuclide renography which may show patho logical changes before clinical alterations. @ The most common pathologic type is the continu 2 0 PG )p 2. 2@ 30 34 31 42 46 50 ous OIH accumulation with the lack of the excre tory phase. This type of renogram was described FIG. 6. RCBFstudyusing“Xeclearance(cadaverkidney,pre served in perfusion chamber). as a sign of rejection by Mobley, et al (6) . Con tinuous OIH accumulation, however, is not pa thognomonic for rejection of kidney transplants. It technique is superior to conventional