Cyclic voiding urosonography for detecting vesicoureteric reflux in renal transplant recipients
Rajko B. Kenda1,,
Anton Kenig2,
Gregor Novljan1,
Rafael Ponikvar3 and
Jadranka Buturovi
Ponikvar3
1 Department of Pediatric Nephrology,
2 Department of Pediatric Radiology and
3 Department of Nephrology, University Medical Center Ljubljana, Ljubljana, Slovenia
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Abstract
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Background. The clinical significance of vesicoureteric reflux (VUR) in renal transplant recipients remains controversial. Voiding urosonography (VUS), a new modality for detecting VUR, can be used in these patients. The sensitivity of X-ray and radionuclide cystography for detecting VUR may be improved with cyclic procedures. The aim of our study was to evaluate whether cyclic VUS is superior to the single-cycle procedure.
Methods. Cyclic VUS was performed in 27 renal transplant recipients. Eight were children or adolescents and the remaining 19 recipients were adults. VUS was performed according to accepted guidelines. After the first micturition, the catheter was left in place and the entire procedure was repeated under the same conditions.
Results. Both initial cycle and cyclic VUS detected 17 out of 27 (63%) VURs in the same patients. The sensitivity was not improved by cyclic VUS. However, there were differences between the initial cycle and cyclic VUS (P=0.028) when comparing the number of negative results and the grades of VURs detected. This difference was even more pronounced when analysing only positive results. In the initial cycle, five out of 17 (29%) VURs were grade III, compared with 10 out of 17 (59%) grade III VURs in the same patients using the cyclic procedure (P=0.008).
Conclusions. Cyclic VUS did not improve the detection sensitivity for VUR in our study. However, given that VUR grade may be important for the management of renal transplant recipients, the use of cyclic VUS may provide a useful diagnostic tool for these patients.
Keywords: cyclic voiding urosonography; renal transplant recipients; vesicoureteric reflux
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Introduction
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The clinical significance of vesicoureteric reflux (VUR) in renal transplant recipients remains controversial. Two methods are routinely used to identify VUR: X-ray voiding cystourethrography (X-ray cystography) and direct radionuclide voiding cystography (radionuclide cystography). Unfortunately, both techniques involve exposure to ionizing radiation. The recent development of commercially available echo-enhancing agents has markedly improved the sonographic detection of fluid movement within the urinary tract [1,2]. This method has made available voiding urosonography (VUS), a reliable alternative to X-ray cystography and radionuclide cystography. Its use for the detection of VUR in children and in renal transplant recipients has been successfully tested in clinical trials [26]. The sensitivity of X-ray cystography and radionuclide cystography in detecting VUR can be improved by using cyclic procedures, such as filling the bladder and having the patient void around the urinary bladder catheter two or more times [710]. The aim of the present study was to evaluate whether cyclic VUS is superior to the single-cycle procedure in paediatric and adult renal transplant recipients.
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Subjects and methods
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Cyclic VUS was performed in 27 kidney transplant recipients, from February to June 2000. Eight of the recipients were children or adolescents, aged 12.218.3 years (mean 16 years) and the remaining 19 were adults, aged 19.254.8 years (mean 39 years). There were 10 male and 17 female patients. In the younger patients, the investigation was a part of the regular post-transplant follow-up, while in the adults VUS was indicated after at least two episodes of urinary tract infection. The Medical Ethics Committee approved the study and written informed consent was obtained from all the patients or parents.
Cyclic voiding urosonography
The investigation was performed using a real-time scanner Accuson XP/10 (Accuson, Mountain View, CA, USA) with a 3.5 MHz and a 7 MHz transducer. The patient was placed in the supine position on an examination table and a baseline ultrasound image of the urinary tract was obtained. The transplanted kidney was evaluated through the ventral approach. A narrow aspiration catheter was inserted into the urinary bladder under aseptic conditions and the urine was allowed to drain. Thereafter, the bladder was slowly filled with saline solution under hydrostatic pressure (4070 cm H2O). The saline solution was infused at body temperature to minimize discomfort. When the predicted bladder volume was reached or when the patient felt an urge to void, Levovist, an echo-enhancing agent (composed of 99.9% microcrystalline galactose microparticles, and 0.1% palmitinic acid) was administered intravesically through the same catheter using a three-way stopcock. A concentration of 300 mg of Levovist/ml in suspension was used. Approximately 11 ml of this suspension was administered per cycle. The bladder and the transplanted kidney with its correspondent ureter were examined by ultrasound while the patient was asked to void around the catheter. During this procedure, the voiding pressure was monitored and voiding continued until the bladder was completely empty. The procedure was then repeated under the same conditions using the same filling volume and the same catheter which was left in place after the first cycle. The voiding pressure was monitored. VUR was acknowledged when hyperechogenic microbubbles were detected in the ureter, in the renal pelvis, or both. VUR was graded as described previously [11]: VUR grade I, microbubbles reaching the ureter only; VUR grade II, microbubbles reaching the pelvis; and VUR grade III, microbubbles reaching the pelvis, which seems dilated.
All patients received chemotherapy for three days to prevent urinary tract infection after catheterization. The data were analysed using chi-square statistics.
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Results
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Results from the initial cycle (conventional VUS), the second cycle, and both cycles combined (cyclic VUS) are summarized in Table 1
. Both the initial cycle and cyclic VUS detected 17 out of 27 (63%) VURs in the same patients, although the second cycle failed to detect one VUR. The sensitivity of VUR detection, regardless of VUR grade, was not improved by cyclic VUS. However, differences between the initial cycle and cyclic VUS were significant (P=0.028) when comparing the number of negative results and the grade of VUR detected (Figure 1
). This difference was even more pronounced when analysing positive results only. In the initial cycle, five out of 17 (29%) VURs were grade III, compared with 10 out of 17 (59%) grade III VURs using the cyclic procedure (P=0.008). Additionally, in certain cases of grade III VUR detected during both cycles, the extent of the pelvic dilatation was markedly increased during the second cycle compared with the initial cycle. No grade I VURs were detected. There were no differences in filling volume or voiding pressure during the cycles. Finally, there were no adverse events associated with Levovist administration.
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Table 1. Incidence and grading of vesicoureteric reflux detected in the first, second, and in both cycles combined during cyclic VUS
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Fig. 1. (a) Sonogram of the transplanted kidney during the initial cycle of cyclic VUS. Microbubbles present in the pyelon are consistent with vesicoureteric reflux grade II. (b) During the second cycle, vesicoureteric reflux grade III was detected in the same transplanted kidney. The pyelon was aboundantly filled with echo-contrast and marked pelvic dilatation was present.
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Discussion
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The incidence of VUR in transplanted kidneys varied from 3.8% to 86% in recent studies [1214]. Such a large variation can be attributed to different surgical techniques, time when VUR was tested, methods used to detect VUR, underlying urological condition, and selection criteria of the study groups. The association between VUR, urinary tract infection, and reflux nephropathy has been well established in paediatric patients with native kidneys. However, less is known about the impact of VUR on long-term graft survival, and the clinical significance of VUR in the transplanted kidney remains controversial.
When testing for VUR in renal transplant recipients, the least aggressive method in terms of radiation exposure is preferred, provided that sensitivity and specificity are comparable to alternative procedures. The majority of these patients have already received a substantial cumulative radiation dose during the course of their illness. In this setting, VUS appears to be a promising alternative to radionuclide cystography and especially to X-ray cystography. In our recent study, 99 children with native kidneys that were suspected of having VUR were investigated simultaneously by radionuclide cystography and VUS [5]. Using radionuclide cystography as the reference, the overall sensitivity and specificity of VUS for detecting VUR were 79% and 92%, respectively. All high grade VURs detected by radionuclide cystography were seen using VUS. A similar study with 23 renal transplant recipients was reported by Kmetec et al. [6]. In comparison with radionuclide cystography, the sensitivity and specificity of VUS for detecting VUR, was 75% and 71%, respectively. Importantly, the accuracy of VUS increased with higher grades of VUR, reaching 100% sensitivity for detecting grade III VUR.
It is noteworthy that both VUS and cyclic VUS were easier to perform in transplanted kidneys than in native kidneys. During the procedure, the attention of the examiner is focused on one kidney. In the supine position, the transplanted kidney is easily accessible to the transducer and there is no need to turn the patient during the procedure.
Although cyclic VUS compared with the first cycle did not improve detection sensitivity for VUR, it revealed higher grades of VUR and an obvious increase in pelvic dilatation in some of our patients. Both cycles were performed under the same conditions using identical voiding patterns. Because the filling volumes and voiding pressures were equal in both cycles, these parameters could not explain the findings. One possible explanation for the higher grades of VUR and the enhanced pelvic dilatation in the second cycle could be an increased compliance of the ureter and the pyelon during the second cycle. Given that VUR grade may be important for the management of renal transplant recipients, the use of cyclic VUS may be helpful, at least in patients showing no VUR or low grade VUR during the initial cycle. From our experience, we believe that in renal transplant recipients with normal cyclic VUS, additional conventional cystography is not mandatory and should not be done. This is true even though VUR may be based on clinical data. Further studies are needed to define the exact role for cyclic VUS compared with VUS and traditional cystographies in diagnosing VUR in renal transplant recipients.
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Acknowledgments
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The study was supported in part by the Slovenian Ministry of Science and Technology (grant: L3-1369-0312/99).
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Notes
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Correspondence and offprint requests to: Professor Rajko Kenda, MD DSc, Head, Department of Nephrology, Pediatric Hospital, University Medical Center, Stare pravde 4, SI-1000 Ljubljana, Slovenia. Email: rajko.kenda{at}mf.uni\|[hyphen]\|lj.si 
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Received for publication: 8. 2.01
Revision received 21. 5.01.