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Nuclear Medicine Error analysis of one s a m p l e clearence methods Dear Sir, The interesting error analysis of one-sample clearance methods by Kotzerke et al. (1992) should not obscure the fact that the errors are small when c o m p a r e d with other methods for measuring renal function that are in widespread clinical use, such as creatinine clearance or blood-free g a m m a - c a m e r a methods. The first single-injection, single-sample m e t h o d o f which we are aware was described by Alestig, H o o d and Vikgren (1966) using unlabelled inulin. A one-sample method using radiolabelled orthoiodohippurate (OIH) was described by Heiskanen, Weber and Graesbeck (1968). The method of Tauxe, discussed at length by Kotzerke et al. (1992), followed in 1971. Since then m a n y similar papers have appeared (our files contain 27 such papers) using not only these agents but also chromium51 ethylene diamine tetra-acetic acid (EDTA), ytterbium-169 diethylene triamine penta-acetic acid (DTPA), technetium-99m D T P A , iodine-131 diatrizoate and 99mTc mercaptoacetyl triglycine (MAG3). By now the capabilities of this a p p r o a c h seem well established on experimental grounds. Theoretical arguments such as those o f Kotzerke et al. must be interpreted in the context o f this b o d y of experimental evidence. Patients with oedema or ascites are usually excluded f r o m such studies. We find no mention o f such exclusion in the p a p e r by Kotzerke et al., which m a y explain their outliers. One or two outliers in a series of 150 patients would not in any case be too surprising, and the correlation coefficient of 0.966 [including the outliers, and covering a range of effective renal plasma flow ( E R P F ) f r o m 50 to 800 ml/min] indicates an adequate performance for clinical use over a wide range of renal function. Kotzerke's data therefore do not justify his conclusion that the one-sample method only holds for normal patients. The statement by Kotzerke et al. that °'The individuals which were used in the study by Tauxe (Tauxe et al. 1971, ~1982) represent healthy adults o f normal weight and kidney function" is simply incorrect. The 1982 p a p e r included a range of E R P F f r o m 0 to 900 ml/min, and patients were not selected for size. It is an empirical fact, though perhaps counter to intuition, that patient size has little effect in applying this m e t h o d to adults if the sample time is chosen appropriately. (The optim u m sample time of 44 min for O I H serves to minimize the effect of patient size for intermediate values of ERPF.) We have examined this in several ways, but not until we included children in the study population (Rus-
Letter to the editor sell et al. 1991) did we find that scaling for size had a decisive influence on the results. We have described two-sample methods (Russell et al. 1985, 1989a, b) for use in research and under other circumstances when special accuracy is needed but continue to use one-sample methods for routine patient care. They are not without error, but in our opinion the errors are acceptable. The insights provided by Kotzerke et al. should be regarded as an aid in interpreting the one-sample methods rather than an argument against their use, since the one-sample methods are simple and practical and remain more accurate than the usual competing methods.
Charles D. Russell Eva V. Dubovsky Division of Nuclear Medicine University of Alabama at Birmingham 619 South 19th Street Birmingham, AL 35233-6835, USA
References Alestig K, Hood B, Vikgren P (1966) Berakning av glomerulusfiltrationen med engangsinjektion av inulin (I). Lakartidningen 63:1554-1559 Heiskanen T, Weber T, Graesbeck R (1968) Determination of I 131hippuric acid renal clearance using single-injection techniques. Scand J Clin Lab Invest 21:211-215 Kotzerke J, Burchert W, Wiese H, von Smekal U, Hundeshagen H (1992) Limitations of clearance determination using the single sample distribution volume method. Eur J Nucl Med 19:1922 Russell CD, Bischoff PG, Kontzen F, Rowell KL, Yester MV, Lloyd LK, Tauxe WN, Dubovsky EV (1985) Measurement of glomerular filtration rate by the single injection method plasma clearance without urine collection: a comparison of single sample, double sample, and multiple sample methods using Tc99m-DTPA and Yb-169-DTPA. J Nucl Med 26:1243-1247 Russell CD, Dubovsky EV, Scott JW (1989 a) Estimation of ERPF in adults from plasma clearance of 1-131 Hippuran using a single injection and one or two blood samples. Nucl Med Biol 16:381-383 Russell CD, Taylor A, Eshima D (1989b) Estimation of Tc-99mMAG3 plasma clearance in adults from one or two blood sampies. J Nucl Med 30:1955-1959 Russell CD, Dubovsky EV, Scott JW (1991) Simplified methods for renal clearance in children: scaling for patient size. J Nucl Med 32:18211825 Tauxe WN, Maher FT, Taylor WF (1971) Effective renal plasma flow: estimation from theoretical volumes of distribution of intravenously injected 131I-orthoiodohippurate. Mayo Clin Proc 46 : 524-532 Tauxe WN, Dubovsky EV, Kidd TE, Diaz F, Smith LR (1982) New formulas for the calculation of effective renal plasma flow. Eur J Nucl Med 7 : 51 54
Eur J Nucl Med (1992) 19:824 © Springer-Verlag 1992
Nuclear Medicine Error analysis of one s a m p l e clearence methods Dear Sir, The interesting error analysis of one-sample clearance methods by Kotzerke et al. (1992) should not obscure the fact that the errors are small when c o m p a r e d with other methods for measuring renal function that are in widespread clinical use, such as creatinine clearance or blood-free g a m m a - c a m e r a methods. The first single-injection, single-sample m e t h o d o f which we are aware was described by Alestig, H o o d and Vikgren (1966) using unlabelled inulin. A one-sample method using radiolabelled orthoiodohippurate (OIH) was described by Heiskanen, Weber and Graesbeck (1968). The method of Tauxe, discussed at length by Kotzerke et al. (1992), followed in 1971. Since then m a n y similar papers have appeared (our files contain 27 such papers) using not only these agents but also chromium51 ethylene diamine tetra-acetic acid (EDTA), ytterbium-169 diethylene triamine penta-acetic acid (DTPA), technetium-99m D T P A , iodine-131 diatrizoate and 99mTc mercaptoacetyl triglycine (MAG3). By now the capabilities of this a p p r o a c h seem well established on experimental grounds. Theoretical arguments such as those o f Kotzerke et al. must be interpreted in the context o f this b o d y of experimental evidence. Patients with oedema or ascites are usually excluded f r o m such studies. We find no mention o f such exclusion in the p a p e r by Kotzerke et al., which m a y explain their outliers. One or two outliers in a series of 150 patients would not in any case be too surprising, and the correlation coefficient of 0.966 [including the outliers, and covering a range of effective renal plasma flow ( E R P F ) f r o m 50 to 800 ml/min] indicates an adequate performance for clinical use over a wide range of renal function. Kotzerke's data therefore do not justify his conclusion that the one-sample method only holds for normal patients. The statement by Kotzerke et al. that °'The individuals which were used in the study by Tauxe (Tauxe et al. 1971, ~1982) represent healthy adults o f normal weight and kidney function" is simply incorrect. The 1982 p a p e r included a range of E R P F f r o m 0 to 900 ml/min, and patients were not selected for size. It is an empirical fact, though perhaps counter to intuition, that patient size has little effect in applying this m e t h o d to adults if the sample time is chosen appropriately. (The optim u m sample time of 44 min for O I H serves to minimize the effect of patient size for intermediate values of ERPF.) We have examined this in several ways, but not until we included children in the study population (Rus-
Letter to the editor sell et al. 1991) did we find that scaling for size had a decisive influence on the results. We have described two-sample methods (Russell et al. 1985, 1989a, b) for use in research and under other circumstances when special accuracy is needed but continue to use one-sample methods for routine patient care. They are not without error, but in our opinion the errors are acceptable. The insights provided by Kotzerke et al. should be regarded as an aid in interpreting the one-sample methods rather than an argument against their use, since the one-sample methods are simple and practical and remain more accurate than the usual competing methods.
Charles D. Russell Eva V. Dubovsky Division of Nuclear Medicine University of Alabama at Birmingham 619 South 19th Street Birmingham, AL 35233-6835, USA
References Alestig K, Hood B, Vikgren P (1966) Berakning av glomerulusfiltrationen med engangsinjektion av inulin (I). Lakartidningen 63:1554-1559 Heiskanen T, Weber T, Graesbeck R (1968) Determination of I 131hippuric acid renal clearance using single-injection techniques. Scand J Clin Lab Invest 21:211-215 Kotzerke J, Burchert W, Wiese H, von Smekal U, Hundeshagen H (1992) Limitations of clearance determination using the single sample distribution volume method. Eur J Nucl Med 19:1922 Russell CD, Bischoff PG, Kontzen F, Rowell KL, Yester MV, Lloyd LK, Tauxe WN, Dubovsky EV (1985) Measurement of glomerular filtration rate by the single injection method plasma clearance without urine collection: a comparison of single sample, double sample, and multiple sample methods using Tc99m-DTPA and Yb-169-DTPA. J Nucl Med 26:1243-1247 Russell CD, Dubovsky EV, Scott JW (1989 a) Estimation of ERPF in adults from plasma clearance of 1-131 Hippuran using a single injection and one or two blood samples. Nucl Med Biol 16:381-383 Russell CD, Taylor A, Eshima D (1989b) Estimation of Tc-99mMAG3 plasma clearance in adults from one or two blood sampies. J Nucl Med 30:1955-1959 Russell CD, Dubovsky EV, Scott JW (1991) Simplified methods for renal clearance in children: scaling for patient size. J Nucl Med 32:18211825 Tauxe WN, Maher FT, Taylor WF (1971) Effective renal plasma flow: estimation from theoretical volumes of distribution of intravenously injected 131I-orthoiodohippurate. Mayo Clin Proc 46 : 524-532 Tauxe WN, Dubovsky EV, Kidd TE, Diaz F, Smith LR (1982) New formulas for the calculation of effective renal plasma flow. Eur J Nucl Med 7 : 51 54
Eur J Nucl Med (1992) 19:824 © Springer-Verlag 1992
