1976, British Journal of Radiology, 49, 794-796

99jcm

_

for the measurement of glomerular filtration rate

By A. J. W. Hilson, M.A., M.B., B.Chir., M.R.C.P., R. D. Mistry, and M. N. Maisey, M.D., M.R.C.P., B.Sc. Department of Nuclear Medicine, Guy's Hospital, London SE1 9RT {ReceivedJanuary, 1976 and in revisedform March, 1976) ABSTRACT

Comparison of the blood clearances of 51Cr—EDTA and "Tc m -Sn-DTPA, in a series of 45 patients with a wide range of glomerular filtration rates, showed that there was a good correlation between the estimates of G.F.R. obtained using the two chelates simultaneously. The single-injection, single-exponential method of G.F.R. estimation was used, with a correction factor of 0.964 for "Tc m -DTPA, which gave a relationship of G.F.R.cr=2.3 + G.F.R.TCml/min with a correlation coefficient of 0.99. "Tc m -DTPA is a suitable agent for the estimation of glomerular filtration rate.

Renal scintigraphy and the measurement of glomerular filtration rate (G.F.R.) are both of great value in the evaluation and follow-up of patients with renal disease. "Tc m -Diethylenetriaminepentaacetic acid (Sn) ( 99 Tc m -DTPA) is an agent widely used for dynamic renal imaging with a gamma camera (Atkins et al., 1973). It has been shown to be handled mainly by glomerular filtration, and preliminary studies in animal and man have suggested that it might be suitable for the measurement of G.F.R. (KJopper et al., 1972). The estimation of the clearance of 51 Cr-EDTA, by the "single-injection, single-exponential" method, as a measure of G.F.R., makes several assumptions but is simple and sufficiently accurate for routine clinical purposes, having an excellent correlation with inulin clearance methods (Garnett et al, 1967; Chantler et al, 1969). This method is now used as the standard in this and many other institutions. The purpose of the present study was to investigate the possible use of the " T c m - D T P A clearance as an alternative to the 51 Cr-EDTA clearance in patients having dynamic renal scintigrams.

for routine measurement of G.F.R. were studied. All had the purpose of the study explained to them and gave their consent. There was no specific preparation of the patients. A 21-gauge Butterfly catheter (Abbott) was inserted in a peripheral vein. One ml of 99TcmDTPA was injected via the catheter, followed by 10 ml 51 Cr-EDTA. The catheter was flushed through with 10 ml of normal saline and then removed. Preliminary tests showed that this method left no residue of either chelate in the catheter. Ten ml samples of blood were taken from the opposite arm into lithium-heparin tubes at approximately two, three and four hours after injection (the exact time interval was noted). Standard solutions were made from the same preparations of 99Tcm-DTPA and 51 Cr-EDTA that had been used for injection. Equal volumes of the standards and plasma were counted in a dualchannel automatic scintillation counter, using pulseheight analysis to separate the 140keV peak of 99Tcm from the 320keV peak of 51Cr. The contribution of the 51Cr in the 99Tcm window was negligible. RESULTS

The figure shows the results obtained. It will be seen that the 45 patients had a range of G.F.R.s from 8.4 ml/min to 154 ml/min. The best-fit straight line, which is shown in the figure, had an equation of

GFR T c =2.9+GFR C r ml/min (1) with a correlation coefficient of 0.99, when a correction factor of 0.964 is used for the calculation of GFRTC in the equation (Chantler and Barratt, 1972) METHODS AND PATIENTS m GFR=0.964VD-1.44T^ (2) " T c - D T P A was prepared from a kit (Diagnostic Isotopes, Inc), using 99Tcm as pertechnetate (Radio- (where GFRcr is the G.F.R. measured with 51 Crchemical Centre) to give an activity of approxi- EDTA, GFR Tc is the G.F.R. measured with mately 100 fid in 1 ml. siCr-EDTA (Radiochemical 99Tc m -DTPA, T | is the half clearance time of the Centre) was diluted with an aqueous solution of 1% exponential, and VD is the apparent volume of benzyl alcohol containing EDTA in a concentration distribution of the tracer). of 1 mg/ml to give an activity of approximately 100 /x,Ci in 10 ml. DISCUSSION For a compound to be suitable for the measureForty-five consecutive patients attending the Department of Nuclear Medicine as out patients ment of the G.F.R., it is necessary to show that the 794

SEPTEMBER 1976 m

"Tc -DTPA

for the measurement of glomerular filtration rate

G.F.R. measured with that agent is the same as the G.F.R. measured simultaneously using an accepted method. This relation must be true over the full clinical range of G.F.R. Such a correlation has been shown for many other chelates, but not for 99Tc m DTPA (Molnar et al, 1971). Correlations have been shown between the G.F.R. measured with "Tc m -DTPAand inulin clearance in dogs (Klopper et al, 1972), between the 9TcmDTPA G.F.R, and endogenous creatinine clearance in man (on different occasions, and with only a fair correlation) (Atkins et al, 1973) and between " T c m - D T P A clearance and 12$I- Iodothalamate clearance (in 11 subjects with a limited range of G.F.R.s) (Klopper et al, 1972). Klopper et al (1972) suggested that 99TcmDTPA may be significantly bound to blood proteins, and that commercial preparations vary from batch to batch in this respect, which would invalidate G.F.R. measurement. Blaufox et al. (1975) state that "the major problems with 99Tc m -DTPA are the complexities of its synthesis and instability in vitro and in vivo". We have shown that the correlation between 99T c m -DTPA clearance and 51 Cr-EDTA clearance is very close over the full range of G.F.R.s measured simultaneously, using several batches of a commercial kit. Having shown that a substance is suitable for the measurement of G.F.R., it is conventional for the results to be presented as numerical values which correspond to the inulin clearance. In the case of the single-injection, single-exponential method this requires correction for such factors as the use of venous, rather than arterial, blood and the use of a single, rather than double, exponential analysis. Chantler and Barrett (1972) showed, empirically, that a composite correction factor of 0.87 gave a result numerically equal to the inulin clearance for 51 Cr-EDTA. The results above show that a correction factor of 0.964 for 9 9 Tc m -DTPA gives a result numerically equal to the corrected value for 5 1 CrEDTA, and thus to inulin. One difference between "Tc m -DTPA and 51 CrEDTA is that the former gives a higher blood activity, particularly when larger doses are used for dynamic imaging. The samples cannot be counted in exactly the same way as when 51 Cr-EDTA is used, as the count rate would be too high. This difficulty can be avoided by allowing the samples to decay for 48-72 hours before counting, or by using smaller samples or a less efficient counter. "Tc m -DTPA has the advantage over other agents for the measurement of G.F.R. that it can be used for imaging. This means that the patient having a

FIG. 1. Simultaneous measurement of G.F.R. with "Tc m -DTPA and 51 Cr-EDTA. The solid straight line has the equation G.F.R.Tc=G.F.R.cr+2.9 ml/min. The dashes indicate the line of identity.

dynamic renal scintigram can have a simultaneous estimation of G.F.R. performed with less radiation dosage and no necessity for a separate visit. There is also a reduction in the number of venepunctures needed, which is often an advantage, particularly in children. The work of Fisher and Veall (1975) also raises the possibility that a single blood sample at a known time after dynamic renal imaging with 99Tc m -DTPA may be all that is necessary for estimation of G.F.R. There are several points of interest arising from our findings. If 99Tc m -DTPA is handled only by glomerular filtration, then the renal image obtained using it is a true "functional" image, reflecting the distribution of glomerular filtration. Also, using the approach of Britton (1975), the ratio of 99T c m DTPA uptake should reflect the division of renal function between the two kidneys, and we are currently investigating this possibility. In conclusion, 9 9Xc m -DTPA is a suitable agent for the routine estimation of G.F.R., as well as being the agent of choice for dynamic renal imaging with the gamma camera, making it the "truly ideal renal function testing radiopharmaceutical" (Blaufox etal, 1975). REFERENCES ATKINS, H. L., KLOPPER, J. F., ECKELMAN, W. C, and RICHARDS, P., 1973. The Technetium-99m-DTPA Renal

Study. In Medical Radioisotope Scintigraphy 1972, Vol. II, pp. 251-261 (I.A.E.A., Vienna). BLAUFOX, D. M., CHERVU, L. R., and FREEMAN, L. M., 1975.

Radiopharmaceuticals for Quantitative Study of Renal Function. In Radiopharmaceuticals, Ed. Subramanian, G., Rhodes, B. A., Cooper, J. F., and Sodd, V. J., pp. 389392 (Society of Nuclear Medicine, New York). BRITTON, K. E., 1975. Renal Function studies with radioisotopes. In Dynamic Studies with Radioisotopes in

795

VOL.

49, No. 585 A. J. W. Hilson, R. D. Mistry and M. N. Maisey

Medicine, 1974, Vol. I, pp. 216-217 (I.A.E.A., Vienna).

GARNETT, E. S., PARSONS, V., and VEALL, N., 1967. Measure-

ment of Glomerular Filtration Rate in man using a 51 Cr/Edetic Acid complex. Lancet, 1, 818-819.

CHANTLER, C , GARNETT, E. S., PARSONS, V., and VEALL, N.,

1969. Glomerular Filtration Rate Measurement in Man by The Single-Injection Method using 51 Cr-EDTA. Clinical Science, 37, 169-180.

KLOPPER, J. F., HAUSER, W., ATKINS, H. L., ECKELMAN, W.

C , and RICHARDS, P., 1972. Evaluation of "Tc m -DTPA for the Measurement of Glomerular Filtration Rate. Journal of Nuclear Medicine, 13,107-110.

CHANTLER, C , and BARRATT, T. M., 1972. Estimation of

Glomerular Filtration Rate from Plasma Clearance of 51Chromium Edetic Acid. Archives of Diseases in Childhood, MOLNAR, G., DAL, I., STUTZEL, M., and JAKY, L., 511971. 47, 613-617. Determination of Glomerular Filtration Rate with Cr, 58Co_ ii4min) ii5m In a n d i«9Yb-Labelled EDTA and FISHER, M., and VEALL, N., 1975. Glomerular Rate EstimDTPA complexes. In Dynamic Studies with Radioisotopes ation Based on a Single Blood Sample. British Medical in Medicine, pp. 358-369 (I.A.E.A., Vienna). Journal, 2, 542.

Book reviews Rational Diagnosis and Treatment. By Henrik R. Wulff, pp. x+182, 1976 (Oxford, London, Edinburgh, Blackwell Scientific Publications), £3-75. This book is not, as the title may suggest, a practical handbook for the management of patients, written for the benefit of muddleheaded clinicians: it deserves the rather longer title required to represent it as a detailed examination of the sources and measurement of uncertainty in clinical decision making. It succeeds very well in explaining why, and to what extent, "experience is fallacious and judgment difficult". Inevitably, definitions are inexact; classifications change; values have ranges of normality, and abnormality is itself a statistical abstraction; causative factors may be necessary, sufficient or contributory; different reports on the same radiograph may be subject to inter- and intra- observer variation and end as informed opinions; there is no avoiding the inexactitudes. These are difficulties which beset and concern a profession whose lot is to make serious decisions on information of limited accuracy, and which is expected to subject to orderly trial the expectations or misgivings to which they are led by complexes of uncertainty; the uncertainty itself must be given a numerical index. This is what the book is about and, as we might expect, it contains a chapter on the purpose and design of clinical trials and an appendix describing the statistical tests commonly encountered in medical journals. The clinical reader, who in any case spends most of his professional life trying to give proper weight to a particular manifestation of disease in relation to a particular diagnosis, may question the virtue of dissecting his mental processes in a way that could decompose what is reasonably described as his art, or which could deprive him of the confidence required to act, as he often must, in the face of uncertainty. He surely understands that, if a disease commonly presents with one or more of three cardinal features, then some patients may display any one, some any two, and some all three. What need has he, then, of a Venn diagram, to illustrate by three overlapping circles that the various contin-

gencies can be represented by areas} The answer is, that he must be prepared to have his acumen processed, to involve himself in information theory and data processing, so that his intracranial software can be got into computer hardware. This book does not pretend to assess the economic consequences or threat of redundancy to be expected from this technological extension of uncertainty: but it will prepare the clinician for the operation without too much pain. H. B. HEWITT.

Diagnostic Ultrasonics—Principles

and use of

Instruments.

ByW. N. McDicken, pp. xii + 320, 1976 (London, Crosby Lockwood, Staples), £15-00. The author's stated objective was to prepare a text which is both comprehensive and technical, yet understandable to non-physicists. There is great need for such a book at the present time, not only because of the rapid growth of diagnostic ultrasound but also because of its inclusion in the radiological and radiographic examinations. The author states "In ultrasonic scanning the highest quality results are achieved only by the logical and scientific manipulation of the machine controls". This book should certainly enable the novice to achieve this aim. The author is to be congratulated on his success in achieving his stated aim but the source of his material has resulted in the book having a close resemblance to a series of lecture notes. This does, however, make it very simple for the reader to extract quickly any particular point of information. This is not a book to be read casually; there is a wealth of information here which should be studied slowly and systematically. Almost every aspect of diagnostic ultrasound is included but the average clinical ultrasonographer will probably find that many of the later chapters can be omitted. The book is strongly recommended to all those involved with diagnostic ultrasound.

796

HYLTON B. MEIRE.

99Tcm-DTPA for the measurement of glomerular filtration rate.

1976, British Journal of Radiology, 49, 794-796 99jcm _ for the measurement of glomerular filtration rate By A. J. W. Hilson, M.A., M.B., B.Chir.,...
357KB Sizes 0 Downloads 0 Views