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Dynamic Renal Scintigraphy in Children With Vesicoureteral Reflux and Suspected Coexisting Ureteropelvic Junction Obstruction
0022-5347/03/1705-1966/0 THE JOURNAL OF UROLOGY® Copyright © 2003 by AMERICAN UROLOGICAL ASSOCIATION
Vol. 170, 1966 –1970, November 2003 Printed in U.S.A.
DOI: 10.1097/01.ju.0000092163.08445.e5
DYNAMIC RENAL SCINTIGRAPHY IN CHILDREN WITH VESICOURETERAL REFLUX AND SUSPECTED COEXISTING URETEROPELVIC JUNCTION OBSTRUCTION JAN STAUSS, LEONARD P. CONNOLLY,* SUSAN A. CONNOLLY, DAVID ZURAKOWSKI, S. TED TREVES AND CRAIG A. PETERS From the Departments of Radiology (Division of Nuclear Medicine) and Urology, Children’s Hospital, Harvard Medical School, Boston, Massachusetts
ABSTRACT
Purpose: We evaluated whether findings on voiding cystourethrography suggesting ureteropelvic junction (UPJ) obstruction coexists with vesicoureteral reflux (VUR) are associated with parameters on dynamic renal scintigraphy that support significant obstruction. Materials and Methods: We reviewed records of 44 patients referred for scintigraphy after voiding cystourethrography performed at age 1 day to 9.4 years (mean 7 months, median 1.7 months) showed VUR and findings suggestive of UPJ obstruction (blockage of contrast material at the UPJ, contrast dilution in the renal pelvis, slow renal pelvic drainage). Results were correlated with Society for Fetal Urology hydronephrosis grade and ureteral morphology. Results: Halftime was in the obstructive range (20 minutes or greater) for 7 of 47 kidneys (15%). The prevalence of a post-furosemide pelvicaliceal drainage halftime in the obstructive range increased with hydronephrosis grade (0% grade 1, 17% grade 2, 50% grade 3 to 4, p ⫽ 0.002) but did not vary with ureteral morphology (p ⫽ 0.08). In 12 of 38 cases (31%) where suspected UPJ obstruction was unilateral and a contralateral kidney was present differential uptake of the affected kidney was less than 45%. The prevalence of differential uptake less than 45% was higher in patients with than without ureteral dilatation (48% vs 12%, p ⫽ 0.02) but did not vary with hydronephrosis grade (p ⫽ 0.93). Conclusions: In children with VUR and suspected coexisting UPJ obstruction dynamic renal scintigraphy may support significant obstruction when hydronephrosis is at least moderate in degree or ureteral dilatation is present but is unlikely to do so if neither is observed. KEY WORDS: ureteral obstruction, vesico-ureteral reflux, kidney/radionuclide imaging
Vesicoureteral reflux (VUR), the most common problem of the lower urinary tract in children, can coexist with ureteropelvic junction (UPJ) obstruction, the most common abnormality of the pediatric upper urinary tract.1 Whether the coexistence is a random event, attributable to a single developmental abnormality or due to ureteral kinking and inflammation caused by VUR has not been established.2, 3 Voiding cystourethrography (VCUG) demonstrates findings that suggest coexistent UPJ obstruction in slightly less than 1% of infants and children with VUR.1, 3 Findings that suggest UPJ obstruction include blockage of refluxed contrast material at the UPJ, dilution of contrast material as it enters the renal pelvis and slow drainage of refluxed contrast material.1, 4 How indicative these findings are of potentially significant obstruction is not known. Over distention of the renal pelvis during VCUG has been cited as a particular pitfall that can lead to over diagnosis of obstruction.2, 5, 6 Because observational management can be appropriate for some patients with hydronephrosis attributed to UPJ obstruction, it seems reasonable to expect that pyeloplasty may not be needed for all degrees of obstruction that coexist with VUR.7–9 Various quantitative parameters derived from dynamic renal scintigraphy are used to determine the significance of obstruction. Among these a high degree of importance has been ascribed to post-furosemide pelvicaliceal
drainage halftime (T1/2) and to differential renal uptake.7, 10 –13 It is not known how closely findings that suggest UPJ obstruction on VCUG are associated with parameters that support significant obstruction on dynamic renal scintigraphy. To address this issue and determine when scintigraphy may be most useful we reviewed our experience with dynamic renal scintigraphy in this setting. MATERIALS AND METHODS
We retrospectively reviewed records of 28 males and 16 females who were consecutively referred for dynamic renal scintigraphy during a 5-year interval after a VCUG was interpreted as showing VUR with coexistent UPJ obstruction. A total of 47 kidneys met the inclusion criteria by having one or more findings suggestive of obstruction on VCUG (dilution of contrast material in the renal pelvis, slow drainage of refluxed contrast material from the renal pelvis, transient blockage of contrast material at the UPJ). In 3 cases the kidney in question was solitary. Patient age ranged from 1 day to 9.4 years at VCUG (mean 7 months, median 1.7 months). Indications for VCUG were hydronephrosis in 38 patients and urinary tract infection in 6, all of whom also had hydronephrosis. Dynamic renal scintigraphy was performed 1 to 65 days (mean 30) after VCUG in all patients. 99m Technetium mercaptoacetyltriglycine in a dose of 7.4 MBq/kg was used for dynamic renal scintigraphy. Patients were hydrated with intravenous normal saline (10 ml/kg per hour) during the examination. If greater than 50% of tracer had not drained from the renal pelvis by 20 minutes after
Accepted for publication June 13, 2003. Study received institutional review board approval. * Corresponding author: Division of Nuclear Medicine, Children’s Hospital, 300 Longwood Ave., Boston, Massachusetts 02115 (telephone: 617-355-7010; FAX: 617-264-9536; e-mail: Leonard. [email protected]). 1966
RENAL SCINTIGRAPHY IN REFLUX AND OBSTRUCTION TABLE 1. Drainage parameters and mean T1/2 in 47 kidneys grouped by hydronephrosis grade No. Hydronephrosis Grade (%)
Drainage Spontaneous Nonobstructive T1/2 Intermediate T1/2 Obstructive T1/2 Mean T1/2 (mins)
1 5 10 3 0 7
(28) (55) (17) (0) ⫾5
2 0 12 7 4 13
(0) (52) (31) (17) ⫾ 15
3–4 0 (0) 0 (0) 3 (50) 3 (50) 55 ⫾ 44
administration, furosemide (1.0 mg/kg) was administered at that time, or, if additional filling of the renal pelvis was needed, later. Imaging was performed on a ␥ camera fitted with a low energy, high resolution collimator. A bladder drainage catheter was in place throughout the examination. Background corrected differential uptake was determined from summation of images obtained 2 to 3 minutes after 99m technetium mercaptoacetyltriglycine administration. Post-furosemide pelvicaliceal drainage T1/2 was calculated using a time-activity curve generated from a region of interest drawn around the renal pelvis and collecting system. T1/2 was defined as the time required from the start of the timeactivity curve’s most rapid descent to a point where an exponential interpolation during monotonic decay crossed a 50% threshold. Values were classified as nonobstructive (less than 10 minutes), intermediate (10 to 19 minutes) or obstructive (20 minutes or greater) in accordance with a recognized consensus.10 Results were correlated with the ultrasono-
1967
graphic grade of hydronephrosis based on a system proposed by the Society for Fetal Urology.14 For statistical analysis 5 cases with grade 3 and 1 with grade 4 hydronephrosis were grouped together in what can be considered a category of severe as opposed to mild (grade 1) or moderate (grade 2) hydronephrosis.8 Scintigraphic parameters were also correlated with ureteral morphology revealed by VCUG. Ureters were subjectively classified as nondilated or dilated. Dilated ureters were further subclassified as being dilated only or tortuous with or without kinking at or near the UPJ. VUR was not graded due to inaccuracy when UPJ obstruction coexists.1, 4 The Pearson chi-square test was used to evaluate associations between T1/2, hydronephrosis grade and ureteral morphologies.15 T1/2 was compared between hydronephrosis grades and ureteral morphologies using the F test in the analysis of variance (ANOVA). Fisher’s exact test was used to compare simple proportions. The Pearson correlation coefficient (r) was done to evaluate the relationship between differential uptake and T1/2. Two-tailed values of p ⬍0.05 were considered statistically significant. Statistical analysis was performed with SPSS for Windows (version 11.0, SPSS Inc., Chicago, Illinois). Continuous data are expressed as mean ⫾ SD. RESULTS
Seven of 47 kidneys (15%) had a T1/2 in the obstructive range. Table 1 provides the number and proportion (percentage) of kidneys with drainage parameters in different ranges
FIG. 1. A, after ultrasonography of 2-month-old female with prenatally detected hydronephrosis showed grade 2 left hydronephrosis, voiding cystourethrography demonstrates bilateral VUR. Delay in refluxed contrast medium entering left renal pelvis was appreciated in real time. B, anteroposterior projection radiograph obtained 30 minutes following void reveals retention of contrast material in dilated left renal pelvis. Post-furosemide images in posterior projection from renal scintigraphy (C) show drainage of left renal pelvis with T1/2 (8 minutes) that is in nonobstructive range (D).
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RENAL SCINTIGRAPHY IN REFLUX AND OBSTRUCTION
and mean T1/2 grouped according to hydronephrosis grade. Results with a T1/2 in the obstructive range were more prevalent (p ⫽ 0.002, Pearson chi-square 20.98 on 6 degrees of freedom), and T1/2 was significantly longer with increasing hydronephrosis grade (p ⬍0.001, F ⫽ 13.61, ANOVA). No kidney with grade 1 hydronephrosis had a T1/2 in the obstructive range. Figures 1 and 2 provide examples of T1/2 in the nonobstructive and obstructive ranges for grade 2 hydronephrosis. Table 2 provides the number and proportion (percentage) of kidneys with drainage parameters in different ranges and mean T1/2 grouped according to ureteral morphology. Neither the prevalence of a T1/2 in the obstructive range (p ⫽ 0.08, Pearson chi-square 15.65 on 9 degrees of freedom) nor mean T1/2 (p ⫽ 0.32, F ⫽ 1.22, ANOVA) varied significantly with ureteral morphology. Assessment of differential uptake was limited to 38 cases in which suspected UPJ obstruction was unilateral and a contralateral kidney was present. Of these 38 kidneys differential uptake was less than 45% in 12 (32%). In 5 of these kidneys (13%) differential uptake was 11% to 35%, and in 1 (3%) it was less than 10%. Table 3 lists the number of patients who had differential uptake assessed and the number (with percent proportion) of those with differential uptake less than 45% according to hydronephrosis grade and ureteral morphology. Prevalence of differential uptake less than 45% (p ⫽ 0.93, Pearson chi-square 0.13 on 2 degrees of freedom) did not vary significantly with hydronephrosis
grade. Prevalence of differential uptake less than 45% was significantly higher (p ⫽ 0.02, Pearson chi-square 5.59 on 1 degree of freedom) in cases with ureteral dilatation. Prevalence of differential uptake less than 45% did not significantly vary between those with dilatation alone, dilatation with tortuosity, and at dilatation with tortuosity and kinking (Pearson chi-square 6.18 on 3 degrees of freedom). The proportions of kidneys with differential uptake less than 45% in 24 cases with and 14 cases without contralateral VUR did not differ significantly (25% vs 43%, p ⫽ 0.30, Fisher’s exact test). No significant correlation between differential uptake and T1/2 was found (Pearson r ⫽ ⫺0.20, p ⫽ 0.24). DISCUSSION
We investigated the association between VCUG findings suggestive of UPJ obstruction with parameters derived from dynamic renal scintigraphy that support significant obstruction. In 15% of cases VCUG findings that suggested coexistent UPJ obstruction were associated with a T1/2 in the obstructive range. Association increased with degree of hydronephrosis, and no kidney with grade 1 hydronephrosis had a T1/2 in the obstructive range. Overall distribution of T1/2 values in the nonobstructive, intermediate and obstructive ranges was similar to what has been reported when UPJ obstruction has been suggested for a wider variety of reasons,
FIG. 2. A, grade 2 left hydronephrosis is demonstrated by ultrasonography in 2-week-old female with prenatally detected hydronephrosis. B, 40 minutes after voiding for VCUG, anteroposterior projection radiograph reveals retained contrast material in hydronephrotic left kidney. Post-furosemide images in posterior projection from renal scintigraphy (C) show slow drainage of left renal pelvis with T1/2 (28 minutes) that is in obstructive range (D).
1969
RENAL SCINTIGRAPHY IN REFLUX AND OBSTRUCTION TABLE 2. Drainage parameters and mean T1/2 in 47 kidneys grouped by ureteral morphology Drainage Spontaneous Nonobstructive T1/2 Intermediate T1/2 Obstructive T1/2 Mean T1/2 (mins)
No. Without Dilatation (%) 2 11 3 4 17
No. Dilatation (%) Overall Dilatation
(10) (55) (15) (20) ⫾ 24
3 11 10 3 17
(11) (41) (37) (11) ⫾ 26
TABLE 3. Patients with differential uptake less than 45% grouped by hydronephrosis grade and ureteral morphology Hydronephrosis: Grade 1 Grade 2 Grade 3–4 Ureteral morphology: No dilatation Overall dilatation: Dilatation only Dilatation ⫹ tortuosity Dilatation ⫹ kinking
No. Pts
No. Uptake Less Than 45% (%)
11 21 6
3 (27) 7 (33) 2 (33)
17 21 9 9 3
2 (12) 10 (48) 4 (44) 4 (44) 2 (67)
mainly hydronephrosis in infants without VUR.16, 17 The occurrence of a T1/2 in the obstructive range did not vary between patients with or without ureteral dilatation, tortuosity and/or kinking. However, any conclusion regarding ureteral kinking, which would reasonably be expected to be associated with slower drainage, must be tempered by the small number of ureters in which kinking was observed. VCUG findings that suggested coexistence of UPJ obstruction with VUR were associated with depressed differential uptake in nearly one-third of kidneys for which this parameter could be meaningfully assessed. A similar observation has been reported in patients who were diagnosed first with UPJ obstruction and later with VUR.18 Because the value of differential uptake as an indicator of functional impairment is decreased when the contralateral kidney is also subject to VUR, the true incidence of functional impairment is likely higher. Depressed uptake might be attributable to damage from VUR, obstruction or both. Alternatively it may reflect a developmental error that leads to renal dysplasia as well as ureteral abnormalities.18, 19 Depressed differential uptake was much more prevalent in cases with ureteral dilatation, while being observed in similar proportions with all grades of hydronephrosis. This observation and a lack of correlation between T1/2 and depressed differential uptake led us to suspect that obstruction was not the central cause of depressed uptake in most cases. It may be best to regard depressed differential uptake as providing further evidence of significant obstruction when T1/2 is prolonged rather than as an independent indicator. What does this study indicate about the use of dynamic renal scintigraphy when VCUG suggests UPJ obstruction coexists with VUR? This question can only be answered in the context of the controversy that surrounds congenital obstruction and the role of dynamic renal scintigraphy in choosing surgical or observational management.7, 9 For practitioners who use T1/2 in guiding management our results indicate that dynamic renal scintigraphy will be most useful when hydronephrosis is of a moderate or greater degree. For those who do not assess T1/2 when hydronephrosis is mild our results will not be surprising but may be reassuring when approaching patients who have not only mild hydronephrosis, but also UPJ obstruction suggested by VCUG. Practitioners who use differential uptake as a deciding factor may find the results of dynamic renal scintigraphy to be most useful for all grades of hydronephrosis when there is ureteral dilatation. A caveat is that the cause of relative functional impairment will not be established by scintigraphy. Neither
Dilatation Only 3 4 5 0 10
(25) (33) (42) (0) ⫾6
Tortuous ⫹ Dilatation
Kinking ⫹ Dilatation
0 (0) 7 (64) 3 (27) 1 (9) 16 ⫾ 28
0 (0) 0 (0) 2 (50) 2 (50) 38 ⫾ 40
practitioners who use drainage T1/2 nor those who use differential uptake in guiding management are likely to gain information from dynamic renal scintigraphy that would discourage observational management when there is only mild hydronephrosis and no ureteral dilatation. Limitations regarding this study must be recognized. First, our choice of quantitative parameters is a simplification of how dynamic renal scintigraphy is performed and interpreted. We have not considered information that is derived from pre or post-diuretic imaging other than T1/2 and differential uptake. In addition, the ranges used to stratify T1/2 results reflect a consensus, and their use in managing UPJ obstruction awaits assessment through a long-term prospective followup study.10 Also, there are multiple methods for calculating T1/2 and results vary with method.10, 16 Furthermore, VCUG findings are subjective and intertwined. We did not attempt to break them down into categories that would indicate greater or lesser importance. Finally, the study does not address use of dynamic renal scintigraphy in management or during followup. In conclusion, in children with VUR and suspected coexistent UPJ obstruction dynamic renal scintigraphy may support significant obstruction when hydronephrosis is at least moderate in degree or ureteral dilatation is present, but is unlikely to do so if neither is observed. REFERENCES
1. Lebowitz, R. L. and Blickman, J. G.: The coexistence of ureteropelvic junction obstruction and reflux. AJR Am J Roentgenol, 140: 231, 1983 2. Hollowell, J. G., Altman, H. G., Snyder, H. M., III and Duckett, J. W.: Coexisting ureteropelvic junction obstruction and vesicoureteral reflux: diagnostic and therapeutic implications. J Urol, 142: 490, 1989 3. Bomalaski, M. D., Hirschl, R. B. and Bloom, D. A.: Vesicoureteral reflux and ureteropelvic junction obstruction: association, treatment options and outcome. J Urol, 157: 969, 1997 4. Barnewolt, C. E., Paltiel, H. J., Lebowitz, R. L. and Kirks, D. R.: Genitourinary tract. In: Practical Pediatric Imaging. Diagnostic Radiology of Infants and Children, 3rd ed. Edited by D. R. Kirks. Philadelphia: Lippincott-Raven Publishers, p. 327, 1997 5. Whitaker, R. H.: Reflux induced pelviureteric obstruction. Br J Urol, 48: 555, 1976 6. Rickard, M. and Whitaker, R. H.: Pelviureteric junction obstruction in association with severe vesicoureteric reflux: a diagnostic dilemma. Urol Radiol, 6: 1, 1984 7. Peters, C. A.: Urinary tract obstruction in children. J Urol, 154: 1874, 1995 8. Onen, A., Jayanthi, V. R. and Koff, S. A.: Long-term followup of prenatally detected severe bilateral newborn hydronephrosis initially managed nonoperatively. J Urol, 168: 1118, 2002 9. Peters, C. A.: Editorial: The long-term followup of prenatally detected severe bilateral newborn hydronephrosis initially managed nonoperatively. J Urol, 168: 1121, 2002 10. Conway, J. J.: “Well-tempered” diuresis renography: its historical development, physiological and technical pitfalls, and standardized technique protocol. Semin Nucl Med, 22: 74, 1992 11. Homsy, Y. L., Saad, F., Laberge, I., Williot, P. and Pison, C.: Transitional hydronephrosis of the newborn and infant. J Urol, 144: 579, 1990 12. Kass, E. J., Majd, M. and Belman, A. B.: Comparison of the diuretic renogram and the pressure perfusion study in children. J Urol, 134: 92, 1985
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RENAL SCINTIGRAPHY IN REFLUX AND OBSTRUCTION
13. Koff, S. A. and Campbell, K. D.: The nonoperative management of unilateral neonatal hydronephrosis: natural history of poorly functioning kidneys. J Urol, 152: 593, 1994 14. Fernbach, S. K., Maizels, M. and Conway, J. J.: Ultrasound grading of hydronephrosis: introduction to the system used by the Society for Fetal Urology. Pediatr Radiol, 23: 478, 1993 15. Fleiss, J. L.: Statistical Methods for Rates and Proportions, 2nd ed. New York: John Wiley, p. 58, 1981 16. Connolly, L. P., Zurakowski, D., Peters, C. A., Dicanzio, J., Ephraim, P., Paltiel, H. J. et al: Variability of diuresis renography interpretation due to method of post-diuretic renal pel-
vic clearance half-time determination. J Urol, 164: 467, 2000 17. Wong, D. C., Rossleigh, M. A. and Farnsworth, R. H.: Diuretic renography with the addition of quantitative gravity-assisted drainage in infants and children. J Nucl Med, 41: 1030, 2000 18. Schuster, T., Stehr, M., Rossmuller, B., Dietz, H. G. and Hahn, K.: Clinical impact of differential renal function to indicate and assess pyeloplasty and the significance of coexisting vesicoureteral reflux. Clin Nucl Med, 26: 923, 2001 19. Mackie, G. G. and Stephens, F. D.: Duplex kidneys: a correlation of renal dysplasia with position of the ureteral orifice. J Urol, 114: 274, 1975
Vol. 170, 1966 –1970, November 2003 Printed in U.S.A.
DOI: 10.1097/01.ju.0000092163.08445.e5
DYNAMIC RENAL SCINTIGRAPHY IN CHILDREN WITH VESICOURETERAL REFLUX AND SUSPECTED COEXISTING URETEROPELVIC JUNCTION OBSTRUCTION JAN STAUSS, LEONARD P. CONNOLLY,* SUSAN A. CONNOLLY, DAVID ZURAKOWSKI, S. TED TREVES AND CRAIG A. PETERS From the Departments of Radiology (Division of Nuclear Medicine) and Urology, Children’s Hospital, Harvard Medical School, Boston, Massachusetts
ABSTRACT
Purpose: We evaluated whether findings on voiding cystourethrography suggesting ureteropelvic junction (UPJ) obstruction coexists with vesicoureteral reflux (VUR) are associated with parameters on dynamic renal scintigraphy that support significant obstruction. Materials and Methods: We reviewed records of 44 patients referred for scintigraphy after voiding cystourethrography performed at age 1 day to 9.4 years (mean 7 months, median 1.7 months) showed VUR and findings suggestive of UPJ obstruction (blockage of contrast material at the UPJ, contrast dilution in the renal pelvis, slow renal pelvic drainage). Results were correlated with Society for Fetal Urology hydronephrosis grade and ureteral morphology. Results: Halftime was in the obstructive range (20 minutes or greater) for 7 of 47 kidneys (15%). The prevalence of a post-furosemide pelvicaliceal drainage halftime in the obstructive range increased with hydronephrosis grade (0% grade 1, 17% grade 2, 50% grade 3 to 4, p ⫽ 0.002) but did not vary with ureteral morphology (p ⫽ 0.08). In 12 of 38 cases (31%) where suspected UPJ obstruction was unilateral and a contralateral kidney was present differential uptake of the affected kidney was less than 45%. The prevalence of differential uptake less than 45% was higher in patients with than without ureteral dilatation (48% vs 12%, p ⫽ 0.02) but did not vary with hydronephrosis grade (p ⫽ 0.93). Conclusions: In children with VUR and suspected coexisting UPJ obstruction dynamic renal scintigraphy may support significant obstruction when hydronephrosis is at least moderate in degree or ureteral dilatation is present but is unlikely to do so if neither is observed. KEY WORDS: ureteral obstruction, vesico-ureteral reflux, kidney/radionuclide imaging
Vesicoureteral reflux (VUR), the most common problem of the lower urinary tract in children, can coexist with ureteropelvic junction (UPJ) obstruction, the most common abnormality of the pediatric upper urinary tract.1 Whether the coexistence is a random event, attributable to a single developmental abnormality or due to ureteral kinking and inflammation caused by VUR has not been established.2, 3 Voiding cystourethrography (VCUG) demonstrates findings that suggest coexistent UPJ obstruction in slightly less than 1% of infants and children with VUR.1, 3 Findings that suggest UPJ obstruction include blockage of refluxed contrast material at the UPJ, dilution of contrast material as it enters the renal pelvis and slow drainage of refluxed contrast material.1, 4 How indicative these findings are of potentially significant obstruction is not known. Over distention of the renal pelvis during VCUG has been cited as a particular pitfall that can lead to over diagnosis of obstruction.2, 5, 6 Because observational management can be appropriate for some patients with hydronephrosis attributed to UPJ obstruction, it seems reasonable to expect that pyeloplasty may not be needed for all degrees of obstruction that coexist with VUR.7–9 Various quantitative parameters derived from dynamic renal scintigraphy are used to determine the significance of obstruction. Among these a high degree of importance has been ascribed to post-furosemide pelvicaliceal
drainage halftime (T1/2) and to differential renal uptake.7, 10 –13 It is not known how closely findings that suggest UPJ obstruction on VCUG are associated with parameters that support significant obstruction on dynamic renal scintigraphy. To address this issue and determine when scintigraphy may be most useful we reviewed our experience with dynamic renal scintigraphy in this setting. MATERIALS AND METHODS
We retrospectively reviewed records of 28 males and 16 females who were consecutively referred for dynamic renal scintigraphy during a 5-year interval after a VCUG was interpreted as showing VUR with coexistent UPJ obstruction. A total of 47 kidneys met the inclusion criteria by having one or more findings suggestive of obstruction on VCUG (dilution of contrast material in the renal pelvis, slow drainage of refluxed contrast material from the renal pelvis, transient blockage of contrast material at the UPJ). In 3 cases the kidney in question was solitary. Patient age ranged from 1 day to 9.4 years at VCUG (mean 7 months, median 1.7 months). Indications for VCUG were hydronephrosis in 38 patients and urinary tract infection in 6, all of whom also had hydronephrosis. Dynamic renal scintigraphy was performed 1 to 65 days (mean 30) after VCUG in all patients. 99m Technetium mercaptoacetyltriglycine in a dose of 7.4 MBq/kg was used for dynamic renal scintigraphy. Patients were hydrated with intravenous normal saline (10 ml/kg per hour) during the examination. If greater than 50% of tracer had not drained from the renal pelvis by 20 minutes after
Accepted for publication June 13, 2003. Study received institutional review board approval. * Corresponding author: Division of Nuclear Medicine, Children’s Hospital, 300 Longwood Ave., Boston, Massachusetts 02115 (telephone: 617-355-7010; FAX: 617-264-9536; e-mail: Leonard. [email protected]). 1966
RENAL SCINTIGRAPHY IN REFLUX AND OBSTRUCTION TABLE 1. Drainage parameters and mean T1/2 in 47 kidneys grouped by hydronephrosis grade No. Hydronephrosis Grade (%)
Drainage Spontaneous Nonobstructive T1/2 Intermediate T1/2 Obstructive T1/2 Mean T1/2 (mins)
1 5 10 3 0 7
(28) (55) (17) (0) ⫾5
2 0 12 7 4 13
(0) (52) (31) (17) ⫾ 15
3–4 0 (0) 0 (0) 3 (50) 3 (50) 55 ⫾ 44
administration, furosemide (1.0 mg/kg) was administered at that time, or, if additional filling of the renal pelvis was needed, later. Imaging was performed on a ␥ camera fitted with a low energy, high resolution collimator. A bladder drainage catheter was in place throughout the examination. Background corrected differential uptake was determined from summation of images obtained 2 to 3 minutes after 99m technetium mercaptoacetyltriglycine administration. Post-furosemide pelvicaliceal drainage T1/2 was calculated using a time-activity curve generated from a region of interest drawn around the renal pelvis and collecting system. T1/2 was defined as the time required from the start of the timeactivity curve’s most rapid descent to a point where an exponential interpolation during monotonic decay crossed a 50% threshold. Values were classified as nonobstructive (less than 10 minutes), intermediate (10 to 19 minutes) or obstructive (20 minutes or greater) in accordance with a recognized consensus.10 Results were correlated with the ultrasono-
1967
graphic grade of hydronephrosis based on a system proposed by the Society for Fetal Urology.14 For statistical analysis 5 cases with grade 3 and 1 with grade 4 hydronephrosis were grouped together in what can be considered a category of severe as opposed to mild (grade 1) or moderate (grade 2) hydronephrosis.8 Scintigraphic parameters were also correlated with ureteral morphology revealed by VCUG. Ureters were subjectively classified as nondilated or dilated. Dilated ureters were further subclassified as being dilated only or tortuous with or without kinking at or near the UPJ. VUR was not graded due to inaccuracy when UPJ obstruction coexists.1, 4 The Pearson chi-square test was used to evaluate associations between T1/2, hydronephrosis grade and ureteral morphologies.15 T1/2 was compared between hydronephrosis grades and ureteral morphologies using the F test in the analysis of variance (ANOVA). Fisher’s exact test was used to compare simple proportions. The Pearson correlation coefficient (r) was done to evaluate the relationship between differential uptake and T1/2. Two-tailed values of p ⬍0.05 were considered statistically significant. Statistical analysis was performed with SPSS for Windows (version 11.0, SPSS Inc., Chicago, Illinois). Continuous data are expressed as mean ⫾ SD. RESULTS
Seven of 47 kidneys (15%) had a T1/2 in the obstructive range. Table 1 provides the number and proportion (percentage) of kidneys with drainage parameters in different ranges
FIG. 1. A, after ultrasonography of 2-month-old female with prenatally detected hydronephrosis showed grade 2 left hydronephrosis, voiding cystourethrography demonstrates bilateral VUR. Delay in refluxed contrast medium entering left renal pelvis was appreciated in real time. B, anteroposterior projection radiograph obtained 30 minutes following void reveals retention of contrast material in dilated left renal pelvis. Post-furosemide images in posterior projection from renal scintigraphy (C) show drainage of left renal pelvis with T1/2 (8 minutes) that is in nonobstructive range (D).
1968
RENAL SCINTIGRAPHY IN REFLUX AND OBSTRUCTION
and mean T1/2 grouped according to hydronephrosis grade. Results with a T1/2 in the obstructive range were more prevalent (p ⫽ 0.002, Pearson chi-square 20.98 on 6 degrees of freedom), and T1/2 was significantly longer with increasing hydronephrosis grade (p ⬍0.001, F ⫽ 13.61, ANOVA). No kidney with grade 1 hydronephrosis had a T1/2 in the obstructive range. Figures 1 and 2 provide examples of T1/2 in the nonobstructive and obstructive ranges for grade 2 hydronephrosis. Table 2 provides the number and proportion (percentage) of kidneys with drainage parameters in different ranges and mean T1/2 grouped according to ureteral morphology. Neither the prevalence of a T1/2 in the obstructive range (p ⫽ 0.08, Pearson chi-square 15.65 on 9 degrees of freedom) nor mean T1/2 (p ⫽ 0.32, F ⫽ 1.22, ANOVA) varied significantly with ureteral morphology. Assessment of differential uptake was limited to 38 cases in which suspected UPJ obstruction was unilateral and a contralateral kidney was present. Of these 38 kidneys differential uptake was less than 45% in 12 (32%). In 5 of these kidneys (13%) differential uptake was 11% to 35%, and in 1 (3%) it was less than 10%. Table 3 lists the number of patients who had differential uptake assessed and the number (with percent proportion) of those with differential uptake less than 45% according to hydronephrosis grade and ureteral morphology. Prevalence of differential uptake less than 45% (p ⫽ 0.93, Pearson chi-square 0.13 on 2 degrees of freedom) did not vary significantly with hydronephrosis
grade. Prevalence of differential uptake less than 45% was significantly higher (p ⫽ 0.02, Pearson chi-square 5.59 on 1 degree of freedom) in cases with ureteral dilatation. Prevalence of differential uptake less than 45% did not significantly vary between those with dilatation alone, dilatation with tortuosity, and at dilatation with tortuosity and kinking (Pearson chi-square 6.18 on 3 degrees of freedom). The proportions of kidneys with differential uptake less than 45% in 24 cases with and 14 cases without contralateral VUR did not differ significantly (25% vs 43%, p ⫽ 0.30, Fisher’s exact test). No significant correlation between differential uptake and T1/2 was found (Pearson r ⫽ ⫺0.20, p ⫽ 0.24). DISCUSSION
We investigated the association between VCUG findings suggestive of UPJ obstruction with parameters derived from dynamic renal scintigraphy that support significant obstruction. In 15% of cases VCUG findings that suggested coexistent UPJ obstruction were associated with a T1/2 in the obstructive range. Association increased with degree of hydronephrosis, and no kidney with grade 1 hydronephrosis had a T1/2 in the obstructive range. Overall distribution of T1/2 values in the nonobstructive, intermediate and obstructive ranges was similar to what has been reported when UPJ obstruction has been suggested for a wider variety of reasons,
FIG. 2. A, grade 2 left hydronephrosis is demonstrated by ultrasonography in 2-week-old female with prenatally detected hydronephrosis. B, 40 minutes after voiding for VCUG, anteroposterior projection radiograph reveals retained contrast material in hydronephrotic left kidney. Post-furosemide images in posterior projection from renal scintigraphy (C) show slow drainage of left renal pelvis with T1/2 (28 minutes) that is in obstructive range (D).
1969
RENAL SCINTIGRAPHY IN REFLUX AND OBSTRUCTION TABLE 2. Drainage parameters and mean T1/2 in 47 kidneys grouped by ureteral morphology Drainage Spontaneous Nonobstructive T1/2 Intermediate T1/2 Obstructive T1/2 Mean T1/2 (mins)
No. Without Dilatation (%) 2 11 3 4 17
No. Dilatation (%) Overall Dilatation
(10) (55) (15) (20) ⫾ 24
3 11 10 3 17
(11) (41) (37) (11) ⫾ 26
TABLE 3. Patients with differential uptake less than 45% grouped by hydronephrosis grade and ureteral morphology Hydronephrosis: Grade 1 Grade 2 Grade 3–4 Ureteral morphology: No dilatation Overall dilatation: Dilatation only Dilatation ⫹ tortuosity Dilatation ⫹ kinking
No. Pts
No. Uptake Less Than 45% (%)
11 21 6
3 (27) 7 (33) 2 (33)
17 21 9 9 3
2 (12) 10 (48) 4 (44) 4 (44) 2 (67)
mainly hydronephrosis in infants without VUR.16, 17 The occurrence of a T1/2 in the obstructive range did not vary between patients with or without ureteral dilatation, tortuosity and/or kinking. However, any conclusion regarding ureteral kinking, which would reasonably be expected to be associated with slower drainage, must be tempered by the small number of ureters in which kinking was observed. VCUG findings that suggested coexistence of UPJ obstruction with VUR were associated with depressed differential uptake in nearly one-third of kidneys for which this parameter could be meaningfully assessed. A similar observation has been reported in patients who were diagnosed first with UPJ obstruction and later with VUR.18 Because the value of differential uptake as an indicator of functional impairment is decreased when the contralateral kidney is also subject to VUR, the true incidence of functional impairment is likely higher. Depressed uptake might be attributable to damage from VUR, obstruction or both. Alternatively it may reflect a developmental error that leads to renal dysplasia as well as ureteral abnormalities.18, 19 Depressed differential uptake was much more prevalent in cases with ureteral dilatation, while being observed in similar proportions with all grades of hydronephrosis. This observation and a lack of correlation between T1/2 and depressed differential uptake led us to suspect that obstruction was not the central cause of depressed uptake in most cases. It may be best to regard depressed differential uptake as providing further evidence of significant obstruction when T1/2 is prolonged rather than as an independent indicator. What does this study indicate about the use of dynamic renal scintigraphy when VCUG suggests UPJ obstruction coexists with VUR? This question can only be answered in the context of the controversy that surrounds congenital obstruction and the role of dynamic renal scintigraphy in choosing surgical or observational management.7, 9 For practitioners who use T1/2 in guiding management our results indicate that dynamic renal scintigraphy will be most useful when hydronephrosis is of a moderate or greater degree. For those who do not assess T1/2 when hydronephrosis is mild our results will not be surprising but may be reassuring when approaching patients who have not only mild hydronephrosis, but also UPJ obstruction suggested by VCUG. Practitioners who use differential uptake as a deciding factor may find the results of dynamic renal scintigraphy to be most useful for all grades of hydronephrosis when there is ureteral dilatation. A caveat is that the cause of relative functional impairment will not be established by scintigraphy. Neither
Dilatation Only 3 4 5 0 10
(25) (33) (42) (0) ⫾6
Tortuous ⫹ Dilatation
Kinking ⫹ Dilatation
0 (0) 7 (64) 3 (27) 1 (9) 16 ⫾ 28
0 (0) 0 (0) 2 (50) 2 (50) 38 ⫾ 40
practitioners who use drainage T1/2 nor those who use differential uptake in guiding management are likely to gain information from dynamic renal scintigraphy that would discourage observational management when there is only mild hydronephrosis and no ureteral dilatation. Limitations regarding this study must be recognized. First, our choice of quantitative parameters is a simplification of how dynamic renal scintigraphy is performed and interpreted. We have not considered information that is derived from pre or post-diuretic imaging other than T1/2 and differential uptake. In addition, the ranges used to stratify T1/2 results reflect a consensus, and their use in managing UPJ obstruction awaits assessment through a long-term prospective followup study.10 Also, there are multiple methods for calculating T1/2 and results vary with method.10, 16 Furthermore, VCUG findings are subjective and intertwined. We did not attempt to break them down into categories that would indicate greater or lesser importance. Finally, the study does not address use of dynamic renal scintigraphy in management or during followup. In conclusion, in children with VUR and suspected coexistent UPJ obstruction dynamic renal scintigraphy may support significant obstruction when hydronephrosis is at least moderate in degree or ureteral dilatation is present, but is unlikely to do so if neither is observed. REFERENCES
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