Duplex kidneys and the risk of urinary tract infection in children

Chon In Kuok · Wun Fung Hui · Winnie Kwai Yu Chan

Duplex kidney, also known as duplicated kidney or renal duplication, is a form of congenital anomaly of kidney and urinary tract (CAKUT) characterized by the presence of two pelvicalyceal systems, dividing a kidney into upper and lower pole moieties. The incidence of duplex kidneys has been reported to be 0.8–1.8% in general population [ 1, 2].Duplex systems can occur in isolation; however, some are complicated by anomalies such as ureterocele, ectopic ureter and vesicoureteral reflux (VUR) [ 3, 4]. These features can potentially lead to recurrent urinary tract infections (UTI)and related long-term morbidities including hypertension and chronic kidney disease [ 5].

Currently, there are a paucity of studies addressing the features and clinical outcomes of duplex kidneys. In this study, we aimed to review the prevalence of associated renal anomalies in duplex kidneys, and identified factors that predict the occurrence of UTI.

We reviewed retrospectively pediatric patients < 18 years old with newly diagnosed duplex kidney between 1st January 2003 and 31st December 2017 in Queen Elizabeth Hospital, Hong Kong. Antenatally detected duplex kidneys that were not confirmed on postnatal ultrasound were excluded.Eligible patients were identified through a diagnosis coding system of the Hospital Authority in Hong Kong. Clinical data on or before 31st December 2018 were analyzed. The development of UTI was the primary outcome of the study.

Hydronephrosis was defined as dilated renal pelvis with maximum anteroposterior diameter (APD) ≥ 5 mm in renal ultrasonography. Renal pelvis with APD between 5 and 9 mm was regarded as mild hydronephrosis, whilst APD ≥ 10 mm was classified as moderate to severe hydronephrosis [ 6]. Duplex kidneys with ectopic ureters or ureteroceles were classified as complicated duplex kidneys.VUR was confirmed by micturating cystourethrogram. The severity of reflux was classified according to the international reflux classification [ 7]. VUR of grade 3 or above was defined as high-grade VUR. Urinary tract infection was diagnosed based on (1) positive bacterial culture from a properly collected urine sample, which included (i) > 10 5 colony forming unit (CFU)/mL of a single uropathogen in clean-catch or mid-stream urine sample, or (ii) > 10 4 CFU/mL of a single uropathogen in catheterized urine sample,and; (2) presence of clinical features including fever and/or urinary symptoms [ 8].

To evaluate the complexity of duplex kidneys, the total number of associated renal anomalies in both kidneys were counted for each patient. These anomalies included (1)moderate to severe grade hydronephrosis (APD ≥ 10 mm),(2) dilated ureter, (3) ureterocele or ectopic ureter, and (4)vesicoureteral reflux. The patients were then stratified into three groups according to the number of co-existing renal anomalies: duplex kidneys with (i) no associated renal anomalies, (ii) 1–2 associated renal anomalies, and (iii)3–4 associated renal anomalies. The time to event was defined as the duration from birth to the development of first UTI. Hazard ratios (HR) with 95% confidence interval(CI) of risk factors were estimated by Cox proportional hazards models.

There were 65 patients (29 boys and 36 girls) with newly diagnosed duplex kidneys during the 15-year study period.Six (9.2%) patients had bilateral duplex kidneys. The associated renal anomalies in duplex kidneys are listed in Table 1.Out of the 59 patients who had unilateral duplex kidney, one patient had renal agenesis on the contralateral side. Other contralateral renal abnormalities included hydronephrosis in 4 patients, VUR in 2 (grade 1 and grade 4, respectively),and multi-cystic dysplastic kidney in 1.

During a median follow-up (IQR) for 63.0 (72.5) months,17 (26.2%) patients developed UTI, with the median age(IQR) of first UTI at 6.0 (7.5) months. Fourteen patients had their first episode of UTI before 1 year old. Among these episodes, Escherichia coli was the causative organism in nearly all patients (16/17; 94.1%), with the remaining one affected by Klebsiella pneumoniae.

Table 1 Features of duplex kidneys ( = 71)

anteroposterior diameter of renal pelvis
a Duplex kidney with ureterocele or ectopic ureter

Variables Frequency (%)Laterality of duplex kidneys Left 43 (66.2%)Right 16 (24.6%)Bilateral 6 (9.2%)Associated renal anomalies Complicated duplex kidney a 13 (18.3%)Hydronephrosis by severity Mild grade (APD 5–9 mm) 19 (26.8%)Moderate to severe grade (APD ≥ 10 mm) 19 (26.8%)Hydronephrosis by moiety Upper moiety 22 (31.0%)Lower moiety 26 (36.6%)Ureteric dilatation 17 (23.9%)Vesicoureteral reflux ( n = 52)Low grade (Grade 1–2) 3 (5.8%)High grade (Grade 3–5) 7 (13.5%)

Table 2 Hazard ratios for urinary tract infection

anteroposterior diameter of renal pelvis
a Duplex kidney with ureterocele or ectopic ureter b Include complicated duplex kidney, moderate to severe hydronephrosis, vesicoureteral reflux and ureteric dilatation* value labeling as bold have statistical significance

Variables Hazard ratio (95% CI) P value*Gender (male) 0.38 (0.13–1.17) 0.093 Bilateral duplex kidneys 1.58 (0.36–6.93) 0.546 Associated anomalies Complicated duplex kidney a 5.32 (2.04–13.91) 0.001 All hydronephrosis (APD ≥ 5 mm) 1.89 (0.67–5.39) 0.231 Moderate to severe hydronephrosis(APD ≥ 10 mm)1.96 (0.75–5.18) 0.173 Vesicoureteral reflux 3.33 (1.17–9.49) 0.024 Ureteric dilatation 3.70 (1.42–9.63) 0.007 Number of associated anomalies b 0 (Reference) 1 –1–2 3.54 (1.08–11.63) 0.037 3–4 6.58 (1.99–21.72) 0.002

The presence of renal anomalies, including ureterocele or ectopic ureters (HR 5.32; 95% CI 2.04–13.91), ureteric dilatation (HR 3.70; 95% CI 1.42–9.63) and vesicoureteral reflux(HR 3.33, 95% CI 1.17–9.49) were significant predictors for UTI (Table 2). Besides, a graded increase in UTI risks with increasing co-existing renal anomalies was also demonstrated.

Surgical interventions were required in 14 (21.5%)patients. Three patients underwent more than 1 surgical operation. The surgical procedures included eight upper nephroureterectomies, six transurethral incisions of ureteroceles, four endoscopic Deflux injections and one ureteral reimplantation.

While some duplex kidneys are regarded as normal variants, we should be aware that renal anomalies are more common in duplex kidneys as compared to single systems[ 4]. Our review demonstrated that duplex kidneys were commonly associated with other renal anomalies. Ureteroceles or ectopic ureters were identified in one-fifth of our patients, a finding similar to another study conducted in Australian population [ 3]. Our cohort had a lower prevalence of VUR (19.3%) as compared to 42–48% in other reviews [ 2, 9].

Besides, we identified that VUR, ureteric dilatation and complicated duplex kidney (ureterocele or ectopic ureter) increased the risk of UTI. The association between ureterocele or megaureter and UTI in duplex kidney was also previously demonstrated [ 10]. Besides that, we also demonstrated a graded increase in the hazard ratios for UTI occurrence with reference to the complexity of duplex kidneys, as denoted by the number of co-existing renal anomalies.

Given the high prevalence of associated renal anomalies in duplex kidneys and their associations with UTI, we suggest that more detailed functional evaluations may be indicated after the initial diagnosis for duplex kidneys for risk stratification. We concurred with other reviews that micturating cystourethrogram (MCUG) are warranted to look for VUR in the urinary systems [ 4, 11].

Several limitations of this study should be addressed.Firstly, a relatively small sample size in this single-centre review limited the power of the study. Secondly, the administration of prophylactic antibiotics, including the choice of drug, dosage and time of initiation were not standardized in our center. Thus, this factor cannot be thoroughly examined in our analysis. These limitations could be addressed by a prospective multi-centre study with guidelines on imaging strategies and prophylactic antibiotics.

Nevertheless, this study, to the best of our knowledge, is the first study to evaluate the characteristics and outcomes of duplex kidneys in Asian pediatric population. Our study demonstrated the importance of detailed evaluation of duplex kidneys, which help to stratify the risks of UTI in these patients. Further research is required to ascertain the role of prophylactic antibiotics and early surgical interventions in UTI prevention in these high-risk patients.

Author contributions

CIK, WFH and WKYC designed the study;CIK and WFH collected and analyzed the data. CIK drafted the manuscripts; WFH and WKYC critically reviewed the manuscript. All authors read and approved the final manuscript.

Funding

None.

Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Declarations

Conflict of interest

No financial or nonfinancial benefits have been received or will be received from any party related directly or indirectly to the subject of this article.

Ethical approval

The study was approved by the Research Ethics Committee (Kowloon Central / Kowloon East Cluster), Hospital Authority,Hong Kong. (Reference: KC/KE-18–0092/ER-1).