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ORIGINAL ARTICLE
Year : 2023 | Volume
: 34
| Issue : 2 | Page : 75-79
Cutoff value of ureteral diameter ratio for predicting spontaneous resolution of vesicoureteral reflux
Shin Mei Wong1, Chi-Shin Tseng2, Jian-Hua Hong3, Kuo-How Huang2, I-Ni Chiang2
1 Department of Urology, College of Medicine, National Taiwan University Hospital, National Taiwan University, Taipei; Division of Urology, Department of Surgery, Cardinal Tien Hospital, New Taipei City, , Taiwan
2 Department of Urology, College of Medicine, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan
3 Department of Urology, College of Medicine, National Taiwan University Hospital, National Taiwan University; Institute of Biomedical Engineering, National Taiwan University, Taipei, Taiwan
Correspondence Address:
I-Ni Chiang
Department of Urology, College of Medicine, National Taiwan University Hospital, National Taiwan University, No. 1, Changde St., Zhongzheng Dist., Taipei 10048
Taiwan
Source of Support: None, Conflict of Interest: None
DOI: 10.4103/UROS.UROS_30_22
Purpose: The five-grade international scale for vesicoureteral reflux (VUR) has been the mainstay for describing VUR severity. The concept of the distal ureteral diameter to the L1–L3 vertebral body distance ratio has been validated. We validated the ureteral diameter ratio (UDR) for predicting VUR outcomes and determined the cutoff value for spontaneous resolution. Materials and Methods: This retrospective review included children with primary VUR and detailed serial voiding cystourethrograms (VCUGs) between March 2005 and December 2016. Patient characteristics, VUR grade, laterality, UDR, laboratory data, and follow-up results were collected. UDR was estimated as the largest distal ureteral diameter within the pelvis divided by the distance of the L1–L3 vertebral bodies. The primary outcome was the prediction of spontaneous VUR resolution. The secondary outcome was the determination of the cutoff value of UDR in the present cohort. Results: We recruited 101 children (59 boys and 42 girls) diagnosed as having primary VUR based on VCUGs at a mean age of 23.48 months. VUR resolved spontaneously in 31 (30.7%) children, 40 (39.6%) children had persistent disease, and 30 (29.7%) received surgical correction. In univariate analysis, laterality, VUR grade, and UDR were significantly associated with spontaneous resolution (P = 0.017, P = 0.026, and P = 0.001, respectively). Multivariate analysis revealed UDR as the prognostic factor for spontaneous VUR resolution (odds ratio, 4.167; P = 0.023). The area under the curve of UDR indicates that the prediction accuracy was 0.74. The optimal cutoff value for UDR in this study was 0.264 (sensitivity, 0.81 and specificity, 0.63). Conclusion: UDR is superior to the VUR grade for predicting spontaneous VUR resolution. Our findings add significant prognostic value for children with primary VUR. A cutoff value of 0.264 may assist with clinical assessment and future management.
Keywords: Articaine, inferior alveolar nerve block, mepivacaine
Vesicoureteral reflux (VUR) has a prevalence of <1% in healthy children and is a common pediatric urology diagnosis.[1] Approximately 30%–50% are diagnosed as having VUR among children with a history of one or more episodes of febrile urinary tract infection (UTI).[2] Patients are often diagnosed when they present with recurrent febrile UTI or on an incidental finding of hydronephrosis. Primary VUR is associated with a failure to prevent urine regurgitation from the bladder and is caused by a congenital anomaly of the ureterovesical junction. Secondary VUR is caused by high intravesical pressure as a result of bladder outlet obstruction, posterior urethral valve, or neurogenic bladder. VUR increases the risks of renal damage, renal fibrotic scarring, hypertension, and even renal failure, with the potentially serious consequence of recurrent febrile UTI.[3]
VUR management remains controversial. The European Association of Urology recommends renal bladder ultrasound after the initial febrile UTI in patients aged 2–24 months.[4] The gold standard for diagnosing VUR remains to be voiding cystourethrography. Introduced in 1981, the International Reflux Study grading system classifies VUR severity into Grades I–V based on the radiographic appearance of the upper urinary tract on voiding cystourethrogram (VCUG). VUR grading is one of the most important predictors of the likelihood of spontaneous resolution in clinical practice, in addition to age, laterality, and sex.[2] The standard approach to low-grade VUR is conservative treatment due to its high spontaneous resolution. Prophylactic antibiotics are considered for those with a high risk of recurrent UTI. However, the rate of spontaneous resolution is not affected by prophylactic antibiotics. The routine use of prophylactic antibiotics in patients with low-grade VUR remains controversial. The resolution rate is high, especially in low-grade VUR patients early in the 1st year of life.[4] Resolution typically spontaneously occurs in Grade I or II VUR patients by the age of 5 years. Only 50% and 9%–25% of cases, respectively, in Grade III or higher VUR display spontaneous resolution.[5] Higher grades are strongly associated with renal scarring in children.[4] VUR grading has been an important prognostic indicator for decades. However, discordance in interobserver and interobserver has been identified.[6],[7] Discrepancy exists, especially in the intermediate grade between the degree of pyelocaliceal system dilatation.[7] Treatment strategies for children diagnosed with intermediate grade VUR are inconclusive, mostly based on assumptions according to grading, child's age, laterality, surgeon experience, patient adherence, and parental preference. The present literature indicates that ureterovesical junction plays an important role in the pathophysiology of primary VUR. In 1903, Sampson described the flap valve as a lock mechanism of the ureterovesical junction.[8] The etiology of primary VUR involves the short intramural length of the ureter, resulting in an incompetent valve-like sphincter that fails to prevent urine backflow. The ureteral diameter ratio (UDR) – estimated as the largest diameter in the false pelvis divided by the distance from L1 to L3 – was first proposed as a parameter for evaluating pediatric VUR in the Pediatric Urology Journal Club.[9] UDR is considered more likely to reflect anatomy in ureterovesical junction (UVJ). Studies have shown UDR superiority in resolution prediction.[10],[11],[12]
We focused on primary VUR in this study, applied and validated UDR as a predictor to get a reasonable clinical utility cutoff value.
Materials and MethodsThe study retrospectively reviewed 101 children with primary VUR and detailed serial VCUGs between March 2005 and December 2016. Patient recruitment, informed consent waiver, and all the study methods were approved by the Institutional Review Board of the National Taiwan University Hospital (#201704024RINA). The inclusion criteria were as follows: children diagnosed with primary VUR having initial VCUG and at least one follow-up VCUG after initial management. Children with known secondary VUR etiology were excluded from the study, such as neurogenic bladder, posterior urethra valve, or concomitant ureteropelvic junction obstruction.
The patients' clinical characteristics, concomitant diseases, laterality of the disease, age at diagnosis, VUR grade, UDR, laboratory data, and follow-up results were collected. VUR grading was determined by radiologists using the International Reflux Study classification system. UDR was estimated as the largest distal ureteral diameter within the pelvis divided by the distance of the L1–L3 vertebral bodies. Spontaneous VUR resolution is defined as a single negative study compared with the initial VCUG under conservative treatment or observation. The prediction of spontaneous VUR resolution was the primary outcome. The cutoff value UDR determination in the present cohort is the secondary outcome.
The Chi-square test compared the categorical variables, while t-test compared the continuous variables. Receiver operating characteristic (ROC) curves were analyzed to determine the overall UDR accuracy in discriminating between spontaneous resolution and persistent hydronephrosis. Multivariable logistic regression was employed to examine the predictive ability of grade, UDR, and laterality for spontaneous resolution. All statistical assessments were considered statistically significant at P < 0.05. Statistical analyses were completed using SPSS statistical software (version 26.0; IBM Corp, SPSS, Inc., Chicago, IL, USA).
ResultsThis study included 101 primary VUR children (59 boys and 42 girls) who met the inclusion criteria. The overall median age was 23.49 months (standard deviation [SD], 52.4), and the overall follow-up median duration was 55.99 months (SD, 40.1). About 30 (29.7%) of the 101 children have received surgical VUR correction, either endoscopic treatment or open repair, and 71 (70.3%) children have received conservative treatment, such as continuous prophylactic antibiotics or observation. [Table 1] shows the surgical and conservation group baseline clinicodemographic characteristics. There was no significant between-group difference in sex, bilaterality, VUR grading, and UDR. The surgical group was older and had a longer follow-up period [Table 1]. At the end of the follow-up period, 31 of the 71 (43.7%) children in the conservation group had spontaneous resolution, while persistent VUR was found in 40 (56.3%) children. [Table 2] compares basic characteristics. The mean resolution time was 49.45 months. The age of VUR diagnosis, gender, VUR grade, and follow-up months did not reach between group significance. Laterality and UDR were significantly different between the spontaneous resolution group and the persistent VUR group [Table 2]. We calculated the overall UDR prognostic performance for detecting spontaneous resolution by the ROC curve, as the area under the curve result was 0.74 (95% confidence interval, 0.623–0.857) [Figure 1]. The optimal cutoff value for high UDR in this study was >0.264 (sensitivity, 0.81 and specificity, 0.63). Accordingly, children were divided into high- and low- risk groups using the UDR 0.264 as a cutoff value. [Table 3] demonstrates the univariate model comparative effect. Laterality, VUR grade and UDR were significantly associated with spontaneous resolution (P = 0.026, 0.017, and 0.001, respectively) [Table 3]. Logistic regression for multivariable analysis revealed that the prognostic factor for spontaneous resolution was UDR (odds ratio [OR], 4.167; P = 0.023), but it is not significant for VUR grade (OR, 1.61; P = 0.444) [Table 4].
Figure 1: ROC of UDR as indicators of spontaneous resolution in primary VUR. VUR: Vesicoureteral reflux, UDR: Ureteral diameter ratio, ROC: Receiver operating characteristic, AUC: Area under the curve Discussion We assessed the VUR grading system performance and UDR in predicting who are less likely to develop spontaneous resolution in this retrospective study involving children with primary VUR. Data from conservation groups were analyzed including age, sex, laterality, VUR grading, and UDR risk stratification. Our findings showed that UDR is a simple and effective parameter for predicting the spontaneous resolution of VUR.
The relationship among VUR, UTIs, pyelonephritis, renal scarring, and impaired renal function was demonstrated in the previous studies.[13] Swerkersson et al. revealed that children <2 years old with febrile UTI and VUR are at risk of renal deterioration.[14] IRGS VUR grading remains a mainstay descriptor of VUR severity, although various factors affect the probability of VUR resolution. VUR grading through radiographic assessment is associated with the risk of inter-rater disagreement, especially for the intermediate grade.[7] VUR grading is based on the dilatation degree of the renal calyx and renal pelvis, and UDR directly reflects the ureterovesical junction incompetence. Higher UDR also indicates the chronic anatomical change of the ureter owing to high reflux pressure over time. Moreover, UDR is more objective with high inter-rater reliability[15] and is more predictive of the risk of febrile UTI.[10],[12],[16] Dangle et al. demonstrated that persistent reflux after voiding and ureter dilatation in an imaging study are strong predictors for those who need surgical intervention.[17] There is no definitive consensus on the timing or indication of surgical VUR treatment. Surgical correction is considered for persistent high-grade VUR according to the European Association of Urology guidelines for VUR.[4] Optimal management involves identifying patients with the greatest risk of VUR and preventing further deterioration of renal function through early intervention. The surgical group children were significantly older than the conservative group in this study. This finding met into our general practice due to the low probability for older child to resolve spontaneously. We stratified the conservative group into low- and high-risk groups according to the UDR cutoff point of 0.264. Univariable analysis revealed that children with bilateral or high-grade VUR were more likely to experience persistent hydronephrosis during follow-up. Our data demonstrated that UDR is superior to VUR grading and laterality in predicting spontaneous resolution. Our multivariate analysis revealed UDR to only be an independent prognostic factor for spontaneous resolution, although VUR grading is a traditionally prognosticating factor for spontaneous resolution. This is probably for children with clinical concerns, a high probability of poor prognosis who might have already undergone surgical correction initially, and excluded from our further analyses.
Several studies have demonstrated that UDR provides additional predictive information for the ultimate clinical outcome in children with VUR. Cooper et al. also suggested that UDR is a better predictor than VUR grade. They found that children with UDR higher than 0.5 did not experience spontaneous resolution in their study.[10] A cutoff value of 0.43–0.45 indicates less likelihood of spontaneous resolution, and the likelihood of persistent VUR increases with every 0.1 unit increase in UDR.[18],[19] Arlen et al. had similar results showing that no child with >0.43 UDR experienced early spontaneous resolution, and a low probability of those with spontaneous resolution had a UDR above 0.35.[19] Children with Grade IV, III, or II VUR were unlikely to have spontaneous resolution if their UDR was >0.25, 0.3, or 0.35, respectively.[10] Furthermore, a previous study demonstrated that increasing UDR was associated with an increased likelihood of febrile UTI over time in children with primary VUR.[12] UDR performed better as a predictor for febrile UTI than VUR grade alone over time.[16] There is no reference range for clinical utility yet, although more studies have proven UDR predictability regardless of the superiority of UDR in predicting the outcome of primary VUR due to the lack of high-level evidence studies. The novelty in this study is to verify a reasonable cutoff value in predicting clinical use outcomes. Early intervention might reduce clinical costs, prevent morbidity, and reduce the long-term health impact among the pediatric population.
The study limitations include a retrospective single-center design, small sample size, and relatively short follow-up period. Information on those without a follow-up VCUG was lacking and they were excluded from this study. The decision for those receiving or not receiving surgical intervention by surgeon or parents was considered an important factor bias, which was excluded from our study. The impact of recurrent UTI episodes, continuous antibiotic prophylaxis rate, and voiding function of children were not addressed in this study. Moreover, the lack of standardized VCUG protocol and standardized follow-up protocol can lead to different duration of spontaneous resolution recorded. The dimercaptosuccinic acid scan is superior to VCUG for the evaluation of parenchymal injury or renal scarring. It is not routinely performed at our institute. However, the strength of this study is that beyond VUR grading, UDR is a superior predictor of the spontaneous resolution of VUR and is applicable for preventing morbidity in this fragile population.
ConclusionsOur study confirmed that UDR has a high prognostic accuracy in predicting spontaneous resolution in children with VUR. Our findings suggest that the combination of the International Reflux Study grading system and UDR can increase prediction for those who need earlier surgical intervention.
Data availability statement
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
References
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