Voiding Cystourethrography – Do We Over-do It?

doi:10.21203/rs.3.rs-4018435/v1

Background: Voiding cystourethrography is primary used to detect vesico-ureteric reflux and is considered “gold standard” diagnostic examination for this condition. It can be ordered by pediatricians, nephrologists, emergency room pediatricians and urologists. Negative effects of Voiding cystourethrographyinclude its invasiveness, radiation exposure and risk of iatrogenic urinary tract infection. Our aim is to determine if we can reduce the number of voiding cystourethrography examinations performed at our Institute.

Methods: Retrospective study was conducted with approval of the Ethical Review Board using clinical data of the patients who underwent voiding cystourethrography over the period of 12 months. Indicators (age of the patient, gender, referring specialist – urologist or nephrologists and indications for voiding cystourethrography) were analyzed using Chi-square, Fisher’s exact and Mann-Whitney test. Possible impact of the above mentioned indicators on the result of the voiding cystourethrography was analyzed using logistic regressive analysis.

Results: Total of 197 voiding cystourethrographies were analyzed. Mann-Whitney U test did not show statistically significant age difference between the patients with normal (median age 3 years) and pathologic (median age 2.5 years) findings on voiding cystourethrography (Z=-0.415, p=0.678). Chi-square test showed that patients with single urinary infection and other indications have a higher chance of normal result on voiding cystourethrography (0.041 and 0.011 respectively). Logistic regressive analysis showed that patients whose referring specialist was

urologist had 2.06 times higher chance for having pathologic finding on voiding cystourethrography (b=-0.810, p=0.007, odds ratio=0.445) compared to those referred by nephrologists.

Conclusions: It is used as the “gold standard” radiographic test to diagnose vesicoureteral reflux. It is however associated by necessary radiation exposure. At our Institute pediatric urologists indicate voiding cystourethrography more cautiously compared to pediatric nephrologists. By avoiding voiding cystourethrography after single urinary tract infection and for other indications we could reduce the number of voiding cystourethrographies performed.

VCUG

urinary tract infection

recurrent urinary tract infection

hydronephrosis

VUR

children

Voiding cystourethrography (VCUG) examination was indicated for all children with urinary tract infection (UTI) two to three decades ago. Complications such as pyelonephritis and kidney damage were thought to be the result of vesicourinary reflux (VUR) of any degree [1]. These days it is well known that most VUR will resolve spontaneously [2] which led to modification of the protocol for performing VCUG examinations.

It is still a matter of debate whether or not VCUG is indicated after only one episode of UTI. This examination is performed to detect high-grade VUR before kidney damage occurs and therefore prevents poor long-term outcome in those patients. Different protocols for VCUG examination in different hospitals prevent doctors from comparing the results and deriving right conclusions. VCUG gives us a clear idea whether to continue with conservative treatment or surgery is needed. In both ways careful follow-up is strongly indicated.

As VCUG is primary used to detect VUR and is considered “gold standard” diagnostic examination for this condition, it can be ordered by pediatricians, nephrologists, emergency room pediatricians and urologists. Negative effects of VCUG include its invasiveness, radiation exposure and risk of iatrogenic UTI. Having this in mind together with the possibility of detecting potentially benign condition led to the conclusion that VCUG should be individualized rather than a routine examination.

The aim of our study was to determine the correlation between the findings on VCUG in relation to age, gender, referring specialist and indications for VCUG in order to see if we could reduce the number of VCUG examinations performed.

A retrospective study was performed at the Institute for Children and Youth Health Care of Vojvodina in Novi Sad. Study was conducted after the approval of the Institutional Ethical Review Board. It conforms to the legal standards and has legal guardian’s written consent according to the Declaration of Helsinki. Clinical data of all patients aged 0 to 18 years who underwent VCUG over the period of 12 months, from January 2015 until January 2016, were collected and analyzed. Data such as age of the patient, gender, referring specialist – urologists or nephrologists, and indications for VCUG were collected. If patient had recurrent UTI followed by hydronephrosis and then scheduled for VCUG examination, only hydronephrosis without UTI was considered indication for the need of this research. All patients underwent standard procedure according to their age while performing VCUG. All follow-up patients continued to be monitored by the same doctor (urologist or nephrologist) who initially indicated VCUG. Every other VCUG for the same patient was indicated by this doctor.

Collected data were then analyzed statistically using IBM SPSS 23 Statistics while the statistically significant results were determined at the level of p < 0.05.

Descriptive methods were used to determine number (N) and percent (%) of categorical variables. The age of the patinets is presented using diagram with mediana and interquartal range (25th – 75th percentile) because Shapiro Wilks test showed that population is not normally distributed (p = 0.000).

Chi-square test and Fischer's exact test were used for the difference between categorical variables and for the age difference we used Mann-Whitney U test. Possible impact on the result of the VCUG was analyzed using logistic regressive analysis.

Total of 197 VCUG examinations were done over the period of 12 months. Statistically significant difference was found when comparing the result of the VCUG (pathologic vs. normal) in relation to the referring specialists (urologists vs. nephrologists) and some indications for the VCUG (follow-up, first UTI and other indications), while there wasn’t statistically significant difference in relation to gender (Table 1).

Table 1. Descriptive values for gender, referring specialist and indications for VCUG based on the pathologic or normal finding on VCUG and in the whole sample

Normal finding on VCUG was more frequently found in male patients, and the once referred by nephrologists but with no statistically significant difference (p > 0.05). The most common indication for VCUG was recurrent UTI, followed by hydronephrosis, but without statistically significant difference between the groups (p > 0.05). Patients who were referred by urologist had a pathological findings on VCUG more frequently (p = 0.041).

Another statistically significant difference was found in the number of children who came for a follow-up; these children had more often pathological finding on VCUG (p<0.001), as could be expected. Unlike these children, children with only one urinary tract infection and other indications for VCUG had a higher chance of having normal finding on VCUG (p<0.05) – Table 1.

Results of the Chi-square test showed that there was not a statistically significant gender difference in relation to the finding on VCUG (χ² = 0.016; df = 1; p = 0.885), but there was a statistically significant difference accoriding to referring specialist (χ² = 5.578; df = 1; p = 0.015). All patients from this study were between 0 and 17 years old with a positive asymmetry indicating larger number of younger children in both groups. In the group with pathological finding on VCUG we found four atypically older children and in the group with normal finding on VCUG there were two older children. Median of the patient’s age in the group with pathological finding on VCUG was 3 years and 2.5 years in the group with normal finding on VCUG. In both groups interquartal range was 6 years (1-7 years) which means that 25% of children were younger than 1 year, and 50% of children were between 1 and 7 years old (Figure 1).

Figure 1. Distribution of the patient’s age in relation to pathological vs. normal finding on VCUG

Results of the Mann-Whitney U test didn’t show statistically significant age difference between patients with normal and pathological finding on VCUG. (Z = - 0.415; p = 0.678) – Figure 2.

Figure 2. Number of patients with a certain age compared in two groups (normal vs. pathological finding on VCUG)

When excluding children who came for the follow-up VCUG and grouping rest of the children in accordance to their age, we found positive asymmetry indicating larger number of younger children in both groups (with normal and pathological finding on VCUG). Median of the patient’s age in the group with pathological finding on VCUG was 2.5 years. 50% of children with normal finding on VCUG were up to 2 years old. There were not statistically significant differences in the patient’s age between these two groups (Z = - 0.769; p = 0.442).

When we excluded 44 patients (22.3%) who were coming for a follow-up VCUG we had 153 patients (77.7%) with following indications for VCUG: UTI, recurrent UTI, hydronephrosis, other. Comparing only these 153 patients in two groups according to their finding on VCUG and in relation to the indication they had for VCUG we didn’t find statistically significant difference between the groups (χ² = 6.338; df = 3; p = 0.096). Neither did we found one in relation to gender (χ² = 1.709; df = 1; p = 0.185) and referring specialist (χ² = 0.004; df = 1; p = 0.865) – Table 2.

There were statistically significantly more normal findings on VCUG in male patients (p < 0.01), in patients with UTI (p < 0.05) and patients who had other indications for VCUG (p < 0.05) when we excluded patients who came for a follow-up VCUG (Table 2).

Table 2. Descriptive values for gender, referring specialist and indications for VCUG in total sample without patients who came for the follow-up VCUG

Table 3 shows statistically significant effect of referring specialist on the finding on VCUG (p < 0.01), while gender and patient’s age didn’t show an effect on the results of VCUG in total sample. In the subgroup without patients who came for the follow-up none of the factors examined (gender, referring specialist and patient’s age) had a significant effect on the result of VCUG (p > 0.05).

Based on the logistic regressive analysis, patients whose referring specialist was urologist rather then nephrologist had 2.06 times higher chance for having pathologic finding on VCUG (b = -0.810, p = 0.007, odds ratio = 0.445).

Since VCUG is usually indicated when there is suspicion of VUR, it is usually done after urinary tract infection. This study shows that it is reasonable to use this diagnostic test after recurrent UTIs, but not after a single UTI.

As we had already mentioned, several decades ago it was believed that VUR would lead to renal damage in children [1]. However, recent studies showed that having VUR does not necessary mean future development of kidney damage [4]. A multicenter, randomized, controlled study by Garin [5] did not find enough evidence for antimicrobial prophylaxis in VUR, nor did a study conducted by Pennesi et al [6].

If most children will have a normal finding on VCUG after single UTI is this invasive test which carries a risk of radiation exposure and iatrogenic UTI really necessary for all of them? This practice started at the end of the XX century when recommendations advised renal and bladder ultrasound (RBUS) after single febrile UTI [1]. Twelve years after VCUG was indicated in children younger than 2 after febrile UTI only if they had hydronephrosis or other findings on RBUS that suggested high-grade VUR [7] according to the revised guideline published by American Academy of Pediatrics (AAP). Therefore, VCUG was indicated in less febrile UTI illnesses. However, this recommendation was not accepted in all hospitals. Some hospitals are still performing VCUG after initial UTI [3] especially in boys. AAP guidelines published in 2011 are recommending VCUG after second UTI or if RBUS showed abnormalities [7]. Additionally, European Association of Pediatics (EAU) recommends VCUG if scarring is presented on dimercaptosuccinic acid (DMSA) scanning [7]. Unlike these two guidelines, National Association of Urology (NICE) guidelines are different in different age groups and dependent on type of UTI [8]. They recommend VCUG after atypical or recurrent UTI in children younger than 6 months.

Doctors indicating and performing VCUG should be informed about inconsistencies in the published literature [9].

Before ordering this diagnostic test clinicians should be aware of its potential risks and benefits. Its benefits include providing more information about the cause of the UTI, presence or absence of VUR and its degree and laterality which can help in management decision (watchful waiting, antibiotic prophylaxis, endoscopic injection or open ureteral reimplantation). Therefore, it can potentially prevent recurrent pyelonephritis and its consequences. However, only minority of children with UTI sent to VCUG would present with severe VUR and therefore benefit from this examination. Most children will present with either low-grade VUR with a high rate of spontaneous resolution or normal finding on VCUG. It is reasonable to raise a question if performing VCUG in children after single UTI is over-diagnosis.

Our study shows that patients who were referred to VCUG by urologist and who had come for the follow-up VCUG have higher chance for pathologic finding on VCUG than the patients who had only one urinary tract infection or other indications for VCUG. Further studies are needed if we wish to decrease the number of unnecessary VCUGs.

ETHICS APPROVAL DECLARATION

This study has been approved by the Ethics commuttee of the Institute for Child and Youth Helath Care of Vojvodina in Novi Sad, Serbia, and the study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments.

CONSENT TO PARTICIPATE

Consent to participate is not applicable.

DATA AVAILABILITY DECLARATION

The datasets analysed during the current study available from the corresponding author on request.

AUTHOR’S CONTRIBUTION

DZ made substantial contributions to the conception and design of the work; MO and MSL helped the acquisition, analysis, and interpretation of data; IF have drafted and substantively revised the work.

All authors have approved the submitted version (and any substantially modified version that involves the author's contribution to the study); AND they agreed both to be personally accountable for the author's own contributions and to ensure that questions related to the accuracy or integrity of any part of the work, even ones in which the author was not personally involved, are appropriately investigated, resolved, and the resolution documented in the literature.

COMPETING INTERESTS

The authors have no conflict of interest.

FUNDING DECLARATION

This research was supported by the Science Fund of the Republic of Serbia,

7295, Development of portable device for continence preservation - Conti4All

Gnech M, 't Hoen L, Zachou A, Bogaert G, Castagnetti M, O'Kelly F, Quaedackers J, Rawashdeh YF, Silay MS, Kennedy U, Skott M, van Uitert A, Yuan Y, Radmayr C, Burgu B. Update and Summary of the European Association of Urology/European Society of Paediatric Urology Paediatric Guidelines on Vesicoureteral Reflux in Children. Eur Urol 2024 Jan 4:S0302-2838(23)03298–0. 10.1016/j.eururo.2023.12.005.
Chirico V, Tripodi F, Lacquaniti A, Monardo P, Conti G, Ascenti G, Chimenz R. Therapeutic Management of Children with Vesicoureteral Reflux. J Clin Med. 2023;13(1):244. 10.3390/jcm13010244.
Palmer BW, Ramji FG, Snyder CT, Hemphill M, Kropp BP, Frimberger D. Voiding cystourethrogram: are our protocols the same? J Urol. 2011;186(4 Suppl.):1668e71. 10.1016/j.juro.2011.04.006, PMID:21855922.
Basiri A, Ziaeefar P, Khoshdel A, Fattahi P, Mafi Balani M, Tofighi Zavareh MA. What are the Effective Factors in Spontaneous Resolution Rate of Primary Vesicoureteral Reflux: A Meta-Analysis and Systematic Review. Urol J. 2023;20(6):385–396. doi: 0.22037/uj. v20i06.8095. PMID: 38158632.
Hari P, Meena J, Kumar M, Sinha A, Thergaonkar RW, Iyengar A, Khandelwal P, Ekambaram S, Pais P, Sharma J, Kanitkar M, Bagga A. Indian Society of Pediatric Nephrology.Evidence-based clinical practice guideline for management of urinary tract infection and primary vesicoureteric reflux. Pediatr Nephrol. 2023 Oct 28. 10.1007/s00467-023-06173-9. PMID: 37897526.
Pennesi M, Travan L, Peratoner L, et al. Is antibiotic prophylaxis in children with vesicoureteral reflux effective in preventing pyelonephritis and renal scars? A randomized, controlled trial. Pediatrics. 2008;121(6):e1489–94. 10.1542/peds.2007-2652. PMID:18490378.
Roberts KB, Downs SM, Finnell SM, Hellerstein S, Shortliffe LD, Wald ER, American Academy of Pediatrics Subcommittee on Urinary Tract Infection and Steering Committee on Quality Improvement and Management, et al. Urinary tract infection: Clinical practice guideline for the diagnosis and management of the initial UTI in febrile infants and children 2 to 24 months. Pediatrics. 2011;128:595–610. 10.1542/peds.2011-1330. PMID:21873693.
National Institute for Health and Clinical Excellence (NICE). Urinary tract infection in children. https://www.nice.org.uk/Guidance/cg54.
Lee LC, Lorenzo AJ, Koyle MA. The role of voiding cystourethrography in the investigation of children with urinary tract infections. Can Urol Assoc J. 2016;10(5–6):210–4. 10.5489/cuaj.3610. PMID:27713802.

Table 1. Descriptive values for gender, referring specialist and indications for VCUG based on the pathologic or normal finding on VCUG and in the whole sample
	Pathological finding on VCUG (N=101)		Normal finding on VCUG (N=96)		Total (N=197)		Significance
	N	%	N	%	N	%	χ²	P
Gender
Male	44	43.6	56	58.3	113	57.4	0.190	0.663
Female	57	56.4	40	41.7	84	42.6	0.009	0.925
Referring specialist
Urologist	58	57.4	38	39.6	96	48.7	4.167	0.041
Nephrologist	43	42.6	58	60.4	101	51.3	2.228	0.136
Indications
Follow-up	39	38.6	5	5.2	44	22.3	26.273	0.000
UTI	1	1.0	9	9.4	10	5.1	6.400	0.011
Recurrent UTIs	35	34.7	43	44.8	78	39.6	0.821	0.365
Hydronephrosis	19	18.8	22	22.9	41	20.8	0.220	0.639
Other	7	6.9	17	17.7	24	12.2	4.167	0.041

Table 2. Descriptive values for gender, referring specialist and indications for VCUG in total sample without patients who came for the follow-up VCUG
	Pathological finding on VCUG (N=62)		Normal finding on VCUG (N=91)		Total (N=153)		Significance
	N	%	N	%	N	%	χ²	P
Gender
Male	30	51.6	55	60.4	85	55.6	7.353	0.007
Female	32	48.4	36	39.6	68	44.4	0.235	0.628
Referring specialist
Urologist	22	35.5	34	37.4	56	36.6	2.571	0.109
Nephrologist	40	64.5	57	62.6	97	63.4	2.979	0.084
Indication for VCUG
UTI	1	1.6	9	9.9	10	5.1	6.400	0.011
Recurrent UTI	35	56.5	43	47.3	78	39.6	0.821	0.365
Hydronephrosis	19	30.6	22	24.2	41	20.8	0.220	0.639
Other	7	11.3	17	18.7	24	12.2	4.167	0.041

Table 3. Binary logistic regressive analysis of the effect of gender, referring specialist and patient’s age on the finding on VCUG
	B	Significance	Odds ratio
All patients (N = 197)
Gender	0.057	0.856	1.059
Referring specialist	-0.810	0.007	0.445
Patient’s age	0.041	0.279	1.042
A group without patients who came for follow-up (N = 153)
Gender	0.598	0.136	1.819
Referring specialist	0.203	0.581	1.225
Patient’s age	0.002	0.960	1.002

Voiding Cystourethrography – Do We Over-do It?

Status:

Version 1

Abstract

Figures

INTRODUCTION

METHODS

RESULTS

DISCUSSION

CONCLUSION

Declarations

References

Tables

Status:

Version 1