- Email: [email protected]
Differential kidney scan in pediatric urology
DIFFERENTIAL
KIDNEY
IN PEDIATRIC
UROLOGY
RAPHAEL
PIERETTI,
DAVID
GILDAY,
ROBERT
JEFFS,
SCAN
M, D
M.D. MD.
From the Department of Surgery, Division of Urology and Department of Radiology, Division of Nuclear Medicine, The Hospital for Sick Children, Toronto. Canada
ABSTRACT-A method was devised to culculate individual kidney function by injecting gg”‘techr~.etium-diethylenetriamine pentaacetic acid, gluconate, or glucoheptonate intravenously and to determine the radioactive uptake by and the contribution of each kidney to tot& renal function. The tested in 13 patients bcy cotnparing the results of the differential kidney accurucy of the method was .scnn with individual kidney creatinine clearance measurements. The method is upplied practically combined with u totul twentu-four-hour creatinine cleurance test. which allows us to ascribe individual creatinine clenrance values to each kidney.
A variety of nuclear medical techniques to measllre individual kidnev function have been devised-these include chlormerodrin uptake, computerized renography, and simple visual comparison of one kidney’s uptake to the other on the scan.‘-’ The pediatric urologist must frequently decide between a reconstructive surgical technique and nephrectomy, especially in the patient in whom renal function is already jeopardized and a nephrectomy would further renal failure. Therefore, the surgeon should know what contribution each kidney makes to total renal function before deciding on treatment modality. To quantitate the contribution of each kidney to total renal function, we measure the amount of radioactivity in each kidney after administering a radiopharmaceutical agent using “regions of interest’. on the gamma camera.* This method, when combined with the twenty-four-hour creatinine clearance test, allows us to ascribe individual creatinine clearance values to each kidllt?Y.
Technique A nuclear angiogram of the kidneys is recorded during the intravenous injection of the bolus of 8.53 mc. per square meter of ggmTc-DPTA (technetium-diethylenetriamine pentaacetic acid), ggmTc-gluconate, or ““mTc-glucoheptonate. Each of the six frames of the angiogram is exposed for four seconds. One minute after injection an image with a density of 1,500 counts per square centimeter is made. All subsequent images up to two hours are exposed for the same time so that variations in density could be related quantitatively to the amount of radionuclide in the field of view of the gamma camera. Additional images are made at three, six, nine, twelve, fifteen, thirty, and sixty minutes and, if necessary, at two and four hours after injection of the radiopharmaceutical agent . The quantitative estimation of the relative amount of functioning renal parenchyma is done in the following manner: from the videotape recording of the data a technologist places symmetric electronic regions of interest around each kidney, and the activity from each kidney is recorcled from one to three minutes. A background count
TABLE I.
Comparison
of differential kidney scan counts with individual creatinine clearance expressed as a percentage of total creatinine clearance*
Diagnosis
Right Kidney cc SC (Per Cent)
Left Kidney cc SC (Per Cent)
1 2 3
Posterior urethral valves Primary megaureter, neurogenic bladder Bilateral reflux and pyelonephritis
59 58 58
51 57 69
41 42 42
49 43 31
; 6
Bilateral Posterior reflux, urethraldysgenetic valves kidneys Posterior urethral valves Right reflux, left ureterovesical obstruction Bilateral reflux, pyelonephritis Hydrocolpos, bilateral hydronephrosis Right ureteropelvic junction obstruction Right ureterovesical junction obstruction Left ureteropelvic junction obstruction Bilateral ureterovesical junction obstruction
23 14 26 56 65 31 48 66 54 71
23 10 26 50 72 26 53 65 52 66
86 77 74 44 35 69 52 34 46 29
90 77
Case Number
7
8 9 10 11 12 13
74
50 28 74 47 35 48 34
SC, differential kidney scan counts; CC, individual kidney creatinine clearance expressed as percentage of total *KEY: creatinine clearance.
one-tenth the area of the initial region of interest is recorded in the flank area inferior to the kidney. The background count area is located to avoid any areas of increased radioactivity due to radioactive urine. The background count Is multiplied by ten and then subtracted from each kidney count. The net count of each kidney is expressed as a percentage of 100 (the total of the two equals 100). The counts are performed twice; the first between one and three minutes after the injection of the radiopharmaceutical agent (early); the second at two to four hours (late). However, if an obstructive lesion is present, the late count is delayed to six or twenty-four hours to minimize the effect At these later times the of urinary stasis. background region of interest location may have to be varied to avoid being placed over an area where radioactive urine is present. Material A total of 56 patients with a variety of urologic conditions were studied using this technique, and sixty-three scans and differential counts were performed. Total creatinine clearance tests were done in all patients. In 13 patients who had undergone nephrostomy or ureterostomy, we were able to measure creatinine clearance on each kidney. After expressing these values as a percentage of total creatinine clearance, that is, as a percentage of total kidney function, the results for each kidney were compared with those obtained by differential kidney scan (Table I). During the
666
postoperative in 3 patients
period the scan was repeated and twice in 2 others.
once
Results In I3 patients individual kidney creatinine clearance stated as a percentage of total creatinine clearance showed a high degree of correlation with individual kidney counts stated as a percentage of total counts. The greatest single disparity between the two differential methods was 11 per cent. The disparity was less than 10 per cent (average 4 per cent) in the other kidneys. Scans repeated in 2 patients, aged seventeen days and five months, showed a 22-per cent improvement of the renal function after surgical relief of obstruction. In another patient, aged eighteen months, the count repeated one year postoperatively showed a slight improvement in function. In 2 other patients, aged eight months and seven years, function remained unchanged following surgical treatment. Comment The use of ggmTc compounds has several advantages over other radioactive pharmaceutical agents. The radiation dose is less, and yet the compound permits a radionuclide angiogram, kidney scan, excretory study, and a magnified view of the kidney with the pin-hole collimator to delineate certain small abnormalities. In addition, for all these observations, ggmTc-gluconate or
UROLOGY
I
DECEMBER
1974 / VOLUME
IV, NUMBER
6
COUNTS RIGHT
LEFT
96%
4%
\J
TOTAL
CLEARANCE
50 ml/m/m2 INDIVIDUAL
CLEARANCE
LEFT
RIGHT 48ml/m/m2
FIGURE 1. Calculation of individual creutinine cleurance. CA) Kidney scintiphoto with counts at three to jke hours showing regions of interest; (B) calculation of
individual clearance.
creatinine
Pml/m /m2
:. A
6
H
tween individual kidney creatinine clearance and differential counts in these I3 patients, we were able to ascribe individual creatinine clearances to each kidney without separate urine collections. In this way the absolute and relative function of each kidney can be measured (Fig. 1). This method is helpful in assessing renal function in patients with vesicoureteral reflux and pyelonephritis, particularly those in whom the damage is more severe on one side. It is also an aid in studying renal function in patients with dysgenetic kidneys, ureteropelvic junction obstruction, uni- or bilateral hydroureteronephrosis in patients with ureterovesical junction posterior urethral valves, obstruction, neurogenic bladder, ectopic ureterocele, prune belly syndrome, and hypertension due to unilateral renal artery disease. We attribute the higher counts found in the repeated scans in 3 of our patients to the improvement of blood supply and kidney function following relief of obstruction. These changes have been demonstrated in many clinical and experimental studies of hydronephrosis and blood flow to the kidney.*-16 The chances of functional improvement are greater in newborn infants than in older children if hydronephrosis is secondary to incomplete obstruction. In early infancy the potential of the kidney to regenerate may be underestimated. An erroneous assumption regarding the functional capacity of the poorer kidney might be made if the surgeon depended only on the roentgenographic appearance, palpation, and visual evaluation of
glucoheptonate compounds are used, only one intravenous injection is required. According to Atkins et ~1.’ and Hauser et a1.6 9gmTc-DTPA is rapidl!, excreted from the body, probably entirely by glomerular filtration. Tubular handling, if present, is insignificant. Approximately 90 per cent is eliminated in twenty-four hours, and only 5 per cent is excreted in the feces. hccording to Boyd et al. 7 “““‘Tc-gluconate or glucoheptonate are largely cleared by glomerular filtration, but some is retained in the renal parenchyms following partial tubular absorption. Initially we used “gmTc-DTPA and early (one to three minutes) differential kidney counts, but more recently we have used ssmTc-gluconate and glucoheptonate and have added the late (two to four hours) kidney count and scan as well. Early and late differential counts vary little in patients without obstruction. The counting is best performed late because approximately 18 per cent of the gluconate or glucoheptonate is bound in the cortex of the kidney by this time. Early counts are important in patients with hydronephrosis, since stasis of urine and accumulation of the radiopharmaceutical agent in the renal pelvis could give an erroneously higher estimation of the kidney’s function. The technique is simple, the calculations easy, and the correlation with kidney function as measured by individual creatinine clearance is close. No computer is required. In applying this method we determine twentyfour-hour creatinine clearance and perform the kidney scan. Because of the close correlation be-
VKOLOGY
i I>E(:EMBER1974 / VOLUME
IV,NUMBER
6
667
the renal parenchyma. In some cases it would be wiser to perform a temporary ureterostomy or nephrostomy and reassess the function of the kidney by the differential kidney scan combined with creatinine clearance tests to determine the degree of functional recovery. We advocate the use of kidney scan and differential counts combined with creatinine clearance tests in those patients in whom an estimation of the function of the individual kidney would help the surgeon to plan treatment. 555 University Avenue Toronto, Ontario, Canada M5G 1X8 (DR. GILDAY) References HOLROYD, A. M., CHISHOLM, G. D., and GLASS, H. The quantitative analysis of renograms using the 1. gamma camera, Phys. Med. Biol. 15: 483 (1970). The renogram BROWN, N. J. G., and BRITTON, K. E.: and its quantitation in radioisotopes in urology and renal disease, Br. J. Ural. 41: 15 (1969). VIVILLE, C., METHLIN, G., and GROB, J. C.: The interest of the quantitative scintigraphy in the appreciation of the separated renal function value, Acta Ural. Belg. 41: 5 (1973). KATHEL, B. L.: Quantitation of the isotope renogram by analogue computer simulation, in Johnston, J. H., and Scholtmeijer, R. J., Eds.: Problems in Paediatric Urology, Excerpta Medica, Amsterdam, 1972, p. 257.
668
5. ATKINS, H. L., et al. : Evaluation of glomerular fiitration rate with ssmTc-DTPA, J. Nucl. Med. 12: 338 (1971). 6. HAUSER, W., et al. : Technetium-s9m DTPA. A new radiopharmaceutical for brain and kidney scanning, Radiology 94: 679 (1970). 7. BOYD, R E., et al. : ssmTc-gIuconate complexes for renal scintigraphy, Br. J. Radiol. 46: 604 (1973). 8. HINMAN, F., Jr.: The pathophysiology of urinary obstruction, in Campbell, M. F., and Harrison, J. H., Eds.: Urology, W. B. Saunders, Philadelphia, 1970, p. 321. 9. IDEM: Recovery of renal function after ureteral deligation, Arch. Surg. 78: 518 (1959). 10. WIDEN, T. : Restitution of kidney function after induced urinary stasis of varying duration, Acta Chir. Stand. 113: 507 (1957). The renal circula11. HERDMAN, J. P., and JACO, N. T.: tion in experimental hydronephrosis, Br. J. Urol. 22: 52 (1950). 12. IDBOHRN, H.: Renal angiography in experimental hydronephrosis, Acta Radiol. 136: 1 (1956). Renal blood flow in 13. IDBOHRN, H., and MUREN, A.: experimental hydronephrosis, Acta Physiol. Stand. 38: 200 (1956). 14. BRUNSCHWIC, A., BARBER, H. R., and ROBERTS, S.: Return of renal function after varying periods of ureteral occlusion. A clinical study, J.A. M.A. 188: 125 (1964). 15. PAPAIOANNOU,A. N., and BRUNSCHWI~, A.: Return of function of a kidney not visualized on intravenous pyelogram for 1?4 years, Arch. Surg. 90: 367 (1965). 16. HODSON, C. J., et al. : Experimental obstructive nephropathy in the pig, Br. J. Ural. 41: 1 (1969).
UROLOGY
/
DECEMBER
1974
/ VOLUME IV, NUMBER 6
KIDNEY
IN PEDIATRIC
UROLOGY
RAPHAEL
PIERETTI,
DAVID
GILDAY,
ROBERT
JEFFS,
SCAN
M, D
M.D. MD.
From the Department of Surgery, Division of Urology and Department of Radiology, Division of Nuclear Medicine, The Hospital for Sick Children, Toronto. Canada
ABSTRACT-A method was devised to culculate individual kidney function by injecting gg”‘techr~.etium-diethylenetriamine pentaacetic acid, gluconate, or glucoheptonate intravenously and to determine the radioactive uptake by and the contribution of each kidney to tot& renal function. The tested in 13 patients bcy cotnparing the results of the differential kidney accurucy of the method was .scnn with individual kidney creatinine clearance measurements. The method is upplied practically combined with u totul twentu-four-hour creatinine cleurance test. which allows us to ascribe individual creatinine clenrance values to each kidney.
A variety of nuclear medical techniques to measllre individual kidnev function have been devised-these include chlormerodrin uptake, computerized renography, and simple visual comparison of one kidney’s uptake to the other on the scan.‘-’ The pediatric urologist must frequently decide between a reconstructive surgical technique and nephrectomy, especially in the patient in whom renal function is already jeopardized and a nephrectomy would further renal failure. Therefore, the surgeon should know what contribution each kidney makes to total renal function before deciding on treatment modality. To quantitate the contribution of each kidney to total renal function, we measure the amount of radioactivity in each kidney after administering a radiopharmaceutical agent using “regions of interest’. on the gamma camera.* This method, when combined with the twenty-four-hour creatinine clearance test, allows us to ascribe individual creatinine clearance values to each kidllt?Y.
Technique A nuclear angiogram of the kidneys is recorded during the intravenous injection of the bolus of 8.53 mc. per square meter of ggmTc-DPTA (technetium-diethylenetriamine pentaacetic acid), ggmTc-gluconate, or ““mTc-glucoheptonate. Each of the six frames of the angiogram is exposed for four seconds. One minute after injection an image with a density of 1,500 counts per square centimeter is made. All subsequent images up to two hours are exposed for the same time so that variations in density could be related quantitatively to the amount of radionuclide in the field of view of the gamma camera. Additional images are made at three, six, nine, twelve, fifteen, thirty, and sixty minutes and, if necessary, at two and four hours after injection of the radiopharmaceutical agent . The quantitative estimation of the relative amount of functioning renal parenchyma is done in the following manner: from the videotape recording of the data a technologist places symmetric electronic regions of interest around each kidney, and the activity from each kidney is recorcled from one to three minutes. A background count
TABLE I.
Comparison
of differential kidney scan counts with individual creatinine clearance expressed as a percentage of total creatinine clearance*
Diagnosis
Right Kidney cc SC (Per Cent)
Left Kidney cc SC (Per Cent)
1 2 3
Posterior urethral valves Primary megaureter, neurogenic bladder Bilateral reflux and pyelonephritis
59 58 58
51 57 69
41 42 42
49 43 31
; 6
Bilateral Posterior reflux, urethraldysgenetic valves kidneys Posterior urethral valves Right reflux, left ureterovesical obstruction Bilateral reflux, pyelonephritis Hydrocolpos, bilateral hydronephrosis Right ureteropelvic junction obstruction Right ureterovesical junction obstruction Left ureteropelvic junction obstruction Bilateral ureterovesical junction obstruction
23 14 26 56 65 31 48 66 54 71
23 10 26 50 72 26 53 65 52 66
86 77 74 44 35 69 52 34 46 29
90 77
Case Number
7
8 9 10 11 12 13
74
50 28 74 47 35 48 34
SC, differential kidney scan counts; CC, individual kidney creatinine clearance expressed as percentage of total *KEY: creatinine clearance.
one-tenth the area of the initial region of interest is recorded in the flank area inferior to the kidney. The background count area is located to avoid any areas of increased radioactivity due to radioactive urine. The background count Is multiplied by ten and then subtracted from each kidney count. The net count of each kidney is expressed as a percentage of 100 (the total of the two equals 100). The counts are performed twice; the first between one and three minutes after the injection of the radiopharmaceutical agent (early); the second at two to four hours (late). However, if an obstructive lesion is present, the late count is delayed to six or twenty-four hours to minimize the effect At these later times the of urinary stasis. background region of interest location may have to be varied to avoid being placed over an area where radioactive urine is present. Material A total of 56 patients with a variety of urologic conditions were studied using this technique, and sixty-three scans and differential counts were performed. Total creatinine clearance tests were done in all patients. In 13 patients who had undergone nephrostomy or ureterostomy, we were able to measure creatinine clearance on each kidney. After expressing these values as a percentage of total creatinine clearance, that is, as a percentage of total kidney function, the results for each kidney were compared with those obtained by differential kidney scan (Table I). During the
666
postoperative in 3 patients
period the scan was repeated and twice in 2 others.
once
Results In I3 patients individual kidney creatinine clearance stated as a percentage of total creatinine clearance showed a high degree of correlation with individual kidney counts stated as a percentage of total counts. The greatest single disparity between the two differential methods was 11 per cent. The disparity was less than 10 per cent (average 4 per cent) in the other kidneys. Scans repeated in 2 patients, aged seventeen days and five months, showed a 22-per cent improvement of the renal function after surgical relief of obstruction. In another patient, aged eighteen months, the count repeated one year postoperatively showed a slight improvement in function. In 2 other patients, aged eight months and seven years, function remained unchanged following surgical treatment. Comment The use of ggmTc compounds has several advantages over other radioactive pharmaceutical agents. The radiation dose is less, and yet the compound permits a radionuclide angiogram, kidney scan, excretory study, and a magnified view of the kidney with the pin-hole collimator to delineate certain small abnormalities. In addition, for all these observations, ggmTc-gluconate or
UROLOGY
I
DECEMBER
1974 / VOLUME
IV, NUMBER
6
COUNTS RIGHT
LEFT
96%
4%
\J
TOTAL
CLEARANCE
50 ml/m/m2 INDIVIDUAL
CLEARANCE
LEFT
RIGHT 48ml/m/m2
FIGURE 1. Calculation of individual creutinine cleurance. CA) Kidney scintiphoto with counts at three to jke hours showing regions of interest; (B) calculation of
individual clearance.
creatinine
Pml/m /m2
:. A
6
H
tween individual kidney creatinine clearance and differential counts in these I3 patients, we were able to ascribe individual creatinine clearances to each kidney without separate urine collections. In this way the absolute and relative function of each kidney can be measured (Fig. 1). This method is helpful in assessing renal function in patients with vesicoureteral reflux and pyelonephritis, particularly those in whom the damage is more severe on one side. It is also an aid in studying renal function in patients with dysgenetic kidneys, ureteropelvic junction obstruction, uni- or bilateral hydroureteronephrosis in patients with ureterovesical junction posterior urethral valves, obstruction, neurogenic bladder, ectopic ureterocele, prune belly syndrome, and hypertension due to unilateral renal artery disease. We attribute the higher counts found in the repeated scans in 3 of our patients to the improvement of blood supply and kidney function following relief of obstruction. These changes have been demonstrated in many clinical and experimental studies of hydronephrosis and blood flow to the kidney.*-16 The chances of functional improvement are greater in newborn infants than in older children if hydronephrosis is secondary to incomplete obstruction. In early infancy the potential of the kidney to regenerate may be underestimated. An erroneous assumption regarding the functional capacity of the poorer kidney might be made if the surgeon depended only on the roentgenographic appearance, palpation, and visual evaluation of
glucoheptonate compounds are used, only one intravenous injection is required. According to Atkins et ~1.’ and Hauser et a1.6 9gmTc-DTPA is rapidl!, excreted from the body, probably entirely by glomerular filtration. Tubular handling, if present, is insignificant. Approximately 90 per cent is eliminated in twenty-four hours, and only 5 per cent is excreted in the feces. hccording to Boyd et al. 7 “““‘Tc-gluconate or glucoheptonate are largely cleared by glomerular filtration, but some is retained in the renal parenchyms following partial tubular absorption. Initially we used “gmTc-DTPA and early (one to three minutes) differential kidney counts, but more recently we have used ssmTc-gluconate and glucoheptonate and have added the late (two to four hours) kidney count and scan as well. Early and late differential counts vary little in patients without obstruction. The counting is best performed late because approximately 18 per cent of the gluconate or glucoheptonate is bound in the cortex of the kidney by this time. Early counts are important in patients with hydronephrosis, since stasis of urine and accumulation of the radiopharmaceutical agent in the renal pelvis could give an erroneously higher estimation of the kidney’s function. The technique is simple, the calculations easy, and the correlation with kidney function as measured by individual creatinine clearance is close. No computer is required. In applying this method we determine twentyfour-hour creatinine clearance and perform the kidney scan. Because of the close correlation be-
VKOLOGY
i I>E(:EMBER1974 / VOLUME
IV,NUMBER
6
667
the renal parenchyma. In some cases it would be wiser to perform a temporary ureterostomy or nephrostomy and reassess the function of the kidney by the differential kidney scan combined with creatinine clearance tests to determine the degree of functional recovery. We advocate the use of kidney scan and differential counts combined with creatinine clearance tests in those patients in whom an estimation of the function of the individual kidney would help the surgeon to plan treatment. 555 University Avenue Toronto, Ontario, Canada M5G 1X8 (DR. GILDAY) References HOLROYD, A. M., CHISHOLM, G. D., and GLASS, H. The quantitative analysis of renograms using the 1. gamma camera, Phys. Med. Biol. 15: 483 (1970). The renogram BROWN, N. J. G., and BRITTON, K. E.: and its quantitation in radioisotopes in urology and renal disease, Br. J. Ural. 41: 15 (1969). VIVILLE, C., METHLIN, G., and GROB, J. C.: The interest of the quantitative scintigraphy in the appreciation of the separated renal function value, Acta Ural. Belg. 41: 5 (1973). KATHEL, B. L.: Quantitation of the isotope renogram by analogue computer simulation, in Johnston, J. H., and Scholtmeijer, R. J., Eds.: Problems in Paediatric Urology, Excerpta Medica, Amsterdam, 1972, p. 257.
668
5. ATKINS, H. L., et al. : Evaluation of glomerular fiitration rate with ssmTc-DTPA, J. Nucl. Med. 12: 338 (1971). 6. HAUSER, W., et al. : Technetium-s9m DTPA. A new radiopharmaceutical for brain and kidney scanning, Radiology 94: 679 (1970). 7. BOYD, R E., et al. : ssmTc-gIuconate complexes for renal scintigraphy, Br. J. Radiol. 46: 604 (1973). 8. HINMAN, F., Jr.: The pathophysiology of urinary obstruction, in Campbell, M. F., and Harrison, J. H., Eds.: Urology, W. B. Saunders, Philadelphia, 1970, p. 321. 9. IDEM: Recovery of renal function after ureteral deligation, Arch. Surg. 78: 518 (1959). 10. WIDEN, T. : Restitution of kidney function after induced urinary stasis of varying duration, Acta Chir. Stand. 113: 507 (1957). The renal circula11. HERDMAN, J. P., and JACO, N. T.: tion in experimental hydronephrosis, Br. J. Urol. 22: 52 (1950). 12. IDBOHRN, H.: Renal angiography in experimental hydronephrosis, Acta Radiol. 136: 1 (1956). Renal blood flow in 13. IDBOHRN, H., and MUREN, A.: experimental hydronephrosis, Acta Physiol. Stand. 38: 200 (1956). 14. BRUNSCHWIC, A., BARBER, H. R., and ROBERTS, S.: Return of renal function after varying periods of ureteral occlusion. A clinical study, J.A. M.A. 188: 125 (1964). 15. PAPAIOANNOU,A. N., and BRUNSCHWI~, A.: Return of function of a kidney not visualized on intravenous pyelogram for 1?4 years, Arch. Surg. 90: 367 (1965). 16. HODSON, C. J., et al. : Experimental obstructive nephropathy in the pig, Br. J. Ural. 41: 1 (1969).
UROLOGY
/
DECEMBER
1974
/ VOLUME IV, NUMBER 6