In the last decade we have witnessed significant progress in the detection and follow‐up of vesicoureteric reflux (VUR) in children. The development has gone simultaneously in two directions: (i) for whom and when it is important to detect VUR, and (ii) introducing new techniques for its detection. Some years ago, X‐ray voiding cystourethrography (VCUG) was not only the gold standard, but actually the only method for detection of VUR. It was followed by direct radionuclide voiding cystography (DRVC). Recently, echo‐enhanced voiding urosonography (VUS) has become a routine procedure in some centres. The objective of this development has been to diminish the radiation burden to the patient, without losing important data.
Generally, it is not only the quality of a procedure (i.e. sensitivity, specificity, radiation, etc.), which determines its acceptability in a routine work‐up. Other parameters appear to play more important roles in decision making, the accessibility of the equipment and the cost of the procedure being only two of them. The introduction of new methods depends largely on personnel, skilled in traditional methods, which they feel confident to perform and also confident to rely on. This is probably the reason why in many centres VCUG has not yet been replaced with DRVC in all justified cases. It can therefore be expected that VUS will be facing the same obstacles in the near future.
Each of the three methods, VCUG, DRVC, and VUS, has its advantages and disadvantages and therefore are not completely interchangeable; there are also some drawbacks common to all three procedures. Lying in supine position on the examination table, surrounded by fearful‐looking machinery and personnel, with a catheter in place and rapid filling of the bladder, can hardly be described as a physiological voiding condition. Furthermore, catheterization is painful and not entirely without risk of iatrogenic infection. The only non‐invasive, ‘physiological’ procedure known so far for the detection of VUR is indirect radionuclide voiding cystography (IRVC), which is more or less a ‘side‐product’ of dynamic renography. Unfortunately it requires a toilet‐trained child, and this alone makes it unsuitable for the majority of children needing investigation. Note that, all VURs that are present only in the filling phase will be missed, since the filling phase of the bladder cannot be studied with IRVC. Considering the reservations on the sensitivity of the IRVC, there is agreement that this technique is contributory only when positive, whereas a negative examination cannot exclude VUR. Also, dynamic renography does not appear to be a first‐line investigation when looking for VUR.
The sensitivity in detecting VUR can be improved with cyclic procedures, i.e. filling the bladder and having the infant void around the catheter two or more times [1–3]. Unlike Polito et al. , who recently advocated cyclic VCUG, we believe that cyclic procedures should only be used with DRVC and VUS because of the unacceptably high radiation burden in cyclic VCUG.
Twenty‐five years ago, Tremewan et al.  reported the use of ultrasonography in four adult patients with high‐grade VUR. Improved techniques were reported using air‐filled microspheres contained either in contrast medium [5,6] or in saline solution . The acoustic properties of these air‐filled microbubbles rendered the urine echogenic and therefore suitable for visualization on a B‐mode scan. Several generations of echo‐enhancing agents have been developed since, each new generation containing smaller and more stable microbubbles. The recent development of these commercially available echo‐enhancing agents has markedly improved the sonographic detection of fluid movement within the urinary tract . The use of echo‐enhanced renal sonography for the detection of VUR in children has already been successfully tested in clinical trials [9–13].
In our study, 99 children aged 1.1 to 12.3 years, with 198 potentially refluxing units were investigated simultaneously by DRVC and VUS . The indications for cystography were urinary‐tract infection, follow‐up of a previously detected VUR, and screening of siblings of children with VUR. During the investigation an echo‐enhancing agent (Levovist) was administered intravesically through a catheter already in place for the DRVC. The movement of both agents, radiotracer and Levovist, was registered simultaneously by a computerized gamma camera and US respectively. The results were analysed, with DRVC representing the reference diagnostic test. The overall sensitivity and specificity of VUS for the detection of VUR were 79 and 92% respectively. The most accurate results were obtained with VUR grade III, where all 33 refluxing units were identified by VUS either as VUR grade III (26/33) or grade II (7/33). The relatively low overall sensitivity of VUS in our series can be explained with some difficulties in interpreting low‐grade VUR by DRVC, especially in small children. For this reason there might have been some misinterpretation of low‐grade VUR (grade I–II) by DRVC. Since the results of DRVC were used as a reference to define the presence or absence of VUR, some cases could have been erroneously labelled as false‐negative results of VUS, rather than false‐positive results of DRVC. Yet it is encouraging that the results of both DRVC and VUS were highly concordant when VURs of higher grades were involved. It is noteworthy that when analysing separately the first and the second halves of the assembled data, the sensitivity rose from 74 to 86% and the specificity from 89 to 94%, stressing the utmost importance of a skilled examiner.
Grading of vesicoureteric reflux
At the 2nd European Meeting on Sonographic Diagnosis of VUR in Heidelberg, Germany (March 2000) it was proposed that the grading of VUR in VUS should be the same as for the VCUG . Although this might have been justified in the era before DRVC, it is probably more appropriate at present to use the same grading as that already in use for DRVC . Divisibility of DRVC and VUS into grades is similar, but it differs from that of VCUG, and in both procedures it is difficult to adopt the five‐grade scale designed for VCUG . Our suggestion therefore is as follows:
(i) VUR grade I: microbubbles (radiotracer) reaching the ureter only.
(ii) VUR grade II: microbubbles (radiotracer) reaching the pelvis.
(iii) VUR grade III: microbubbles (radiotracer) reaching the pelvis, which appears to be dilated.
Indications for voiding urosonography
With the introduction of DRVC, the indications for VCUG have been significantly reduced due to higher sensitivity and significantly lower radiation burden of the former. We believe that one should aim at introducing VUS instead of DRVC, rather than VCUG, and leave VCUG for those cases where the procedure has proved to be superior to DRVC, since the urethra can only be visualized with VCUG. It is noteworthy that the accessibility of ultrasound equipment is much broader than that of nuclear medicine facilities and therefore much larger numbers of patients might benefit from VUS than DRVC.
VUS is also a suitable method of detecting VUR in transplanted kidneys, in both children and adults . In comparison to the VUS of native kidneys it is easier to perform, because during the whole procedure the examiner's attention is focused on one kidney only. 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.
In the search for new ‘patient‐friendly’ techniques the best possible detection of VUR should also be an ongoing process. Hopefully, VUS is only one of the steps along the way. It is possible that the next development will be VUS with the use of wide‐band harmonic imaging . The data gathered so far suggest that in expert hands VUS may be a reliable method for detecting and following VUR in children and in patients with renal grafts. We hope that further studies will help to define the exact place of VUS with respect to traditional cystography procedures.
Correspondence and offprint requests to: Prof. Rajko Kenda MD DSc, Department of Nephrology, Children's Hospital, University Medical Center Ljubljana, Stare pravde 4, 1000 Ljubljana, Slovenia.