The Use of Sequential 197Hg Chlormerodrin Delayed Scans to Evaluate and to Follow Individual Renal Function

Vol. 112. October Printed in U.S.A.

THE JOURNAL OF UROLOGY

Copyright © 1974 by The Williams & Wilkins Co.

THE USE OF SEQUENTIAL 197 HG CHLORMERODRIN DELAYED SCANS TO EV ALU ATE AND TO FOLLOW INDIVIDUAL RENAL FUNCTION WILLIAM F. GADBOIS

AND

JOSEPH N. CORRIERE, JR.*

From the Division of Urology, Department of Surgery and Harrison Department of Surgical Research, University of Pennsylvania, Philadelphia, Pennsylvania

Bilateral ureteral catheterization is the only way to accurately determine and follow individual renal function. Unfortunately, minor complications occur in 20 per cent of the patients so studied, major complications occur in 5 per cent and about half of the studies, even when carefully performed, are technically unsatisfactory. 1 • 2 Radiomercury chlormerodrin has been shown to bind the sulfhydryl groups of functioning renal tubules with accumulation depending predominantly on renal blood flow and efficiency of tubular extraction. 3 • 4 Maximum tubular binding occurs 48 hours after injection and remains virtually constant for 13 days. At that time the material is slowly released into the urine. 5 Recently, various authors have used radiomercury compounds and external radionuclide scanning to evaluate individual renal function.•-• Few have compared their results to conventional clearances and none has Accepted for publication March 22, 1974. Supported in part by United States Public Health Service Grants 5 ROl AM15279-02 and 5 ROl GM16248-15. * Requests for reprints: Suite W-310, Hospital of University of Pennsylvania, 3400 Spruce Street, Philadelphia, Pennsylvania 19104. 1 Dahl, D. S., O'Conor, V. J., Jr., Walker, C. D. and Simon, N. M.: The morbidity of differential renal function studies. Analysis of 271 studies. J.A.M.A., 202: 857, 1967. 2 Fritjofsson, A. and Aurell, M.: Bilateral renal clearance. Technical problems and the effect of ureteric catheterization on renal function. Scand. J. Ural. Nephral., 2: 103, 1968. 'Laakso, L., Lindgren, I. and Rekonen, A.: Radiomercury and rat kidney: an autoradiographic study with neohydrin-203 Hg. Acta Radio!., 3: 304, 1965. 4 Reba, R. C., Wagner, H. N., Jr. and McAfee, J. G.: Measurement of Hg 20 ' chlormeradrin accumulation by the kidneys for detection of unilateral renal disease. Radiology, 79: 134, 1962. 5 Raynaud, C., Desgrez, A., Kellershohn, C., Ricard, S., Girault, M. and Blons, M.: Measurement of renal mercury uptake by external counting: separate functional testing of each kidney. J. Ural., 99: 248, 1968. 'Johnston, G. S., Wettlaufer, J. N. and Murphy, G. P.: Clinical and experimental studies using HG-197 neohydrin as a measure of renal blood flow. J. Ural., 92: 378, 1964. 7 Raynaud, C., Ricard, S., Karam, Y. and Kellershohn, C.: The use of the renal uptake of 197 Hg as a method for testing the functional value of each kidney. J. Nucl. Med., 11: 125, 1970. 'Schlegel, J. U., Varela, R. and Stanton, J. J.: Individual renal plasma flow determination without ureteral catheterization. J. Ural., 96: 20, 1966. 'Tabern, D. L., Kearney, J. and Sohn, H.: The quantitative measurement of tubular chlormeradrin binding as an index of renal function: a study of 400 cases. Canad. Med. Ass. J ., 103: 601, 1970.

studied their subjects sequentially to assess the accuracy of these techniques in following the function of a renal unit in time. The reproducibility of delayed (48-hour) sequential 197 Hg chlormerodrin renal scans is evaluated herein and the results with standard clearance determinations are correlated. MATERIALS AND METHODS

Bifid bladder preparations were created in 7 female mongrel dogs by our previously described technique 10 to allow for collection of urine from each kidney. After a 1-month stabilization period differential renal clearances of endogenous creatinine, inulin and para-aminohippuric acid (PAH) were done by the standard procedures in each dog, every 2 months for 6 months under light pentobarbital anesthesia. Excretory urograms were done prior to study and midway through the protocol to ensure the continued presence of a normal urinary tract. Within 1 week of each clearance, renal scans were done 48 hours after the intravenous injection of 250 ,uci. 197Hg chlormerodrin using a pho-gamma camera interfaced with a varian digital computer. Counts over each kidney were printed out on a memorex computer terminal and the raw scan counts of the left and right kidneys were compared. The raw scan counts for the same kidney were also compared from scan to scan. The data were then expressed as percentage of total function contributed by the left kidney (per cent left). A similar calculation (per cent left) was determined for the creatinine, inulin and PAH clearances. RESULTS

Table 1 is a summary of the conventional clearances. The total clearance values (left kidney plus right kidney) are listed with standard deviations to document the reproducibility of our technique as well as the percentage of the total clearance contributed by the left kidney (per cent left). The raw counts from the left and right kidneys during each of the 3 scanning sessions as well as the per cent left values are listed in table 2. The mean percentage of total function contributed by the left kidney for the entire series of experiments was 50.97 plus or minus 1.95 for ' 0 Preate, D. L., Corriere, J. N. and Murphy, J. J.: A successful canine bifid bladder preparation for repeated long-term individual renal function studies. J. Surg. Res., 13: 245, 1972.

420

USE OF SEQUENTIAL

197 HG

creatinine, 51.26 plus or minus 1.46 for inulin, 51.30 plus or minus 1.43 for PAH and 55.60 plus or minus 2.62 for 197 Hg chlormerodrin. The order of per cent difference was 19.3 for creatinine, 8.8 for inulin and 17 .2 for P AH. The individual animal and total group variations for the per cent left

TABLE

Dog

Clearance

Creatinine Inulin

PAH Creatinine Inulin

PAH :l

Creatinine Inulin

PAH 4

Creatinine lnulin

PAH ;)

Creatinine Inulin

PAH 6

Creatinine lnulin

PAI-! 7

Creatinine lnulin

PAI-! Totals

Creatinine lnulin

PAI-!

values and standard deviation of the various ies can be better appreciated in figures 1 and There was no correlation between the ravv scan counts for the same kidney from scan probably because the injected chlormerodrin has a built-in radioactive substances.

1. Conventional clearances

I

2

421

CHLORMERODRIN DELAYED SCANS IN INDIVIDUAL RENAL FUNCTION

l

TABLE

Mean Total Clearance (cc/min.I ± Standard Deviation

Mean Clearance 1r;; lt .) = Standard De\'iation

48.17"' :U8 46.27 " 2.42 101.08 ~ 12.:34 39.60 ~ 1:J.14 94.81 " 16.21 89.6, , 18 7iJ 46.71 ± 2.49 52.:iO ct- 3.ciO 101.12 = 16.26 4;,_3;3 ± I !.I I 6:l.91 = 1.81 129.88 = 26.72 45.58 ±

5.2G

.'il.6, ± 2.,2 102.28 + i:3.011 56 ,;i,'i + 10 76 1:i:u:1 ± 3:l.91 ~ :il..'i.S + 87.10"' 4,5.12 ,56.52

106.:39

2,,.82 fa02 11.78 15.00

8.,2

L j_ C

4.99 18.27

50.,50 ii0.95 49.8:l 49.00 50.00 50.40 cil.60 50.85 51.80 49.27 51.5.S :i2.,.5

.C

o :Jr,

3

Percent

:J.929 3.248

3,856 1,8,ll

I 2 :1

:l ..547 4.:101 3,581

:J.,41

:J

.l. ()_];)

4

± 1. lii 5:1 ..'):1 !· 0./7 .s:3.00 = 0.20 50 .4:3 I O.49 48.9:l " 0.4.'i 49.60 ± 0.70 50.lOt0.10 54.00 ± :l.04 .52.8,5 ± 4.:i,-, ;i.3.80 T :l.l:J

50.9, 51.26 oI .:JO

2 3

2

0.99

:u,

F>

Left

fi,.:l

5:3.3 51.2 55.5

4.192 :1.001 :J.:l()fj

58.1 56.l 56.6

3,08:i J,475 :J.911

2,421 2,.557 2.769

60.:3 ;)/ .G 58.:)

:1

G,92:2 4,074 4,196

3.4:12 :l.28, :l.476

6:l.:3 55.;) 5f">.1

2 3

:l.38, :),781 3.165

2,86:l :3.:H):i 3.102

I 2

:i 1

6

2 7

1 .-!:3

Kidney

Function

I CI P Hg

:'i6.9:J ..L O il;i

57.97

±

:3_7g

5'.Z.G7 , l .f";/_~

Total ---~----~-~L ---~---~---------

I.

CI P Hg CI P Hg

48.7 5:3.:l

5.824 :l,841 4,312

= 1.9,, = U6 ±.

:us:i

6:Ls

2,67~

:1

of

5:3.2 50.5

12.485 10.947 :J,860 :l.680 2.991 2.:WJ

1 2

Mean St anclar
Rt.

J:l.620 12.00,,

.1

±

%Lt.

Scan

2.82

i

J.

Hg chlormerodrin renal scans

Lt.

2

±

197

Counts Dog

:3.25 :3.:16 2.02 1.2-l 0.80 L\o

± ± ± c

2.

CI P Hg CI P Hg CI P Hg CI P Hg

4

Total

FIG.

6

CI P Hg

422

GADBOIS AND CORRIERE Standard Deviations of Renal Function Studies (% Left)

CI P Hg

Total

C I P Hg

CI P Hg

C IP Hg

CI P Hg

CI P Hg

2

3

4

5

CI P Hg

6

CI P Hg

7

FIG. 2

DISCUSSION

In most centers renal scanning with radiomercury compounds involves scanning from 1 to 4 hours after the intravenous administration of the particular radionuclide. However, this is the least reliable section of the curve because the radioactivity in the kidney is still accumulating during this time and it is difficult to separate renal accumulation from that of other organs, especially the liver and spleen. 5 In addition, collecting system error owing to urine radioactivity is introduced when the scan is done prior to 48 hours. After that time the urine is usually no longer radioactive. 8 From our results it appears that 48-hour delayed 197 Hg chlormerodrin renal scans, like conventional renal clearances, are still subject to an inherent biological variability. Davies and Shock found that inulin and diodrast clearances may vary as much as 20 to 25 per cent even from collection period to collection period within the same clearance study .1 1 However, our data suggest that the variability of the 197 Hg chlormerodrin scans is of the same order as the conventional studies and, therefore, can be used to follow individual renal function. The only disturbing finding is that in all of our dogs the left kidney had consistently higher scan counts than the right one when compared to the conventional data (averaged 55.6 versus 51.2 per 11 Davies, D. F. and Shock, N. W.: The variability of measurement of inulin and diodrast tests of kidney function. J. Clin. Invest., 29: 491, 1950.

cent). Raynaud and associates also observed this phenomenon and suggested that this may be caused by a shielding effect by the liver on the right side. 5 • 7 Other authors have described a much closer correlation among either 203 Hg or 197 Hg chlormerodrin renal uptake and renal blood flow, 6 • 8 renal tubular function 9 or inulin and PAH clearances. 5 • 7 Practically speaking, these mean values are not statistically different in our study. Finally, it should be noted that since the kidneys have roughly equal function in normal animals minor variations in function or technique will tend to skew the results far more than if the function of 1 kidney were much more than the other. Since the latter situation is more likely to be present in a patient who would be considered for individual renal function analysis, the minor variations presented here would probably become inconsequential and the data more meaningful. We plan to pursue this aspect of investigation. SUMMARY

Conventional split renal clearances and 197 Hg chlormerodrin delayed scans were done on 7 dogs every 2 months for 6 months. The mean percentage of total function contributed by the left kidney was 50.97 plus or minus 1.95 for creatinine, 51.26 plus or minus 1.46 for inulin, 51.30 plus or minus 1.43 for PAH and 55.60 plus or minus 2.62 for 197 Hg chlormerodrin. This range of reproducibility suggests that scans can be used to follow individual renal function.