Inuence of Febrile Urinary Tract Infection on Ultrasonic Measurements of Nonreux Upper Urinary Tract Dilation in Infants

Background To investigate the changes in ultrasonic measurements of nonreux upper urinary tract dilation in infants with febrile urinary tract infection (UTI). Methods There were 28 cases of nonreux upper urinary tract dilatation with febrile UTI: 14 cases of ureteropelvic junction obstruction (UPJO) (14 kidneys) and 14 cases of ureterovesical junction obstruction (UVJO) (16 kidneys). Changes in anteroposterior renal pelvic diameter (APD) and ureteral dilatation during infection and after infection were compared in UPJO and UVJO patients, respectively. Results In the UPJO with febrile UTI group, the APD was 24.1±10.0 mm at the time of UTI and 16.6±7.0 mm 1 week after infection recovery (P<0.001). In the UVJO with febrile UTI group, the APD was 19.3±8.5 mm at the time of UTI and 15.2±7.7 mm 1 week after infection recovery (P<0.001). In the UVJO with febrile UTI group, the ureteric diameter was 11.0±3.2 mm during UTI and 6.8±2.6 mm 1 week after infection recovery (P<0.001). the APD diameter decreased after UTI treatment compared with that during infection.


Introduction
In infants, upper urinary tract dilatation due to upper urinary tract obstruction affects kidney function and can lead to urinary tract infection (UTI) if progression continues (1)(2)(3). The rst two most common causes of upper urinary tract dilatation in infants are ureteropelvic junction obstruction (UPJO) and ureterovesical junction obstruction (UVJO) (2). Ultrasound is a commonly used follow-up method (2,4,5).
One surgical indication for upper urinary tract dilatation is an increase in the anteroposterior renal pelvic diameter (APD) or ureteric diameter during follow-up (2). One animal experiment suggested that ureteral contraction could be reversibly inhibited by bacteria in the ureteral lumen(6). Another animal study demonstrated that the combination of infection and obstructive hydronephrosis caused renal pelvic pressure elevation that was higher than that associated with either infection or obstructive hydronephrosis alone (7). Upper UTIs often have systemic symptoms such as fever(8-10). Our purpose is to investigate the changes in ultrasonic measurements of nonre ux upper urinary tract dilation in infants with febrile UTI.

Patients And Methods
Retrospective analysis was performed on cases of patients with nonre ux upper urinary tract dilatation combined with febrile UTI who were followed and treated in our hospital from June 2015 to June 2020.
The exclusion criteria were dysplastic or hyperechogenic kidney, megaureter caused by vesicoureteral re ux, posterior urethral valves, and neurogenic bladder. All patients were uncircumcised.
Patients were divided into UPJO and UVJO groups. Changes in the APD and ureteral dilatation during infection and after infection were compared in the two groups.
Ultrasonic examination of the urinary system was performed in the supine position after adequate oral hydration. The APD was de ned as the diameter at which the kidney was measured in the transverse plane at the mid-level of the kidney (11). The upper, middle and lower ureteric diameters were measured, and the mean values of the three values were taken. Measurements were taken once during and once after infection. Hydration status, bladder lling, and operator skills in uence the results of ultrasound measurements (5). All ultrasound measurements were performed by the same well-trained sonographer.
The timing of measurement was when the bladder was full after oral liquid intake (water, milk or juice) at 15 ml/kg body weight (12).
The diagnosis of febrile UTI included the following criteria: fever exceeding 38 degrees Celsius, pyuria (positive leukocyte esterase, greater than 5 white blood cells per high-power eld) and urine culture (> 10 5 cfu/mL of voided urine of a single microorganism in a specimen collected by clean-catch urine collection)(2).
Intravenous antibiotics and ultrasound examinations were performed immediately after the diagnosis of febrile UTI. Ultrasound examination and voiding cystourethrography were performed one week after the body temperature was normal, pyuria disappeared, and urine bacteria culture was negative.

Statistical analysis
The K-S test was used to test normality. Spearman rank correlation analysis was used to analyze the correlation of data. The difference in the rst and second ultrasonic measurement results was analyzed by paired-samples T tests. SPSS version 26 was used for statistical analysis. P values less than 0.05 were considered statistically signi cant.

Patient characteristics
A total of 14 febrile UTIs occurred in 289 follow-up UPJO patients. Age range: 1 month to 4 years, median: 7 months (3 months to 2 years and 10 months old, interquartile range). All 14 patients had unilateral hydronephrosis in a total of 14 kidneys. There were 2 patients with grade I vesicoureteral re ux, and no ureteral dilatation was measured by ultrasound.
A total of 14 febrile UTIs occurred in 67 follow-up UVJO patients. Age range: 2 months to 5 years, median: 11 months (4 months to 1 year and 11 months old, interquartile range). There were 2 patients with bilateral hydroureteronephrosis and bilateral infections in a total of 16 kidneys.

Ultrasound outcomes
In the UPJO with febrile UTI group, the APD was 24.1 ± 10.0 mm at the time of UTI and 16.6 ± 7.0 mm 1 week after infection recovery (P < 0.001) (paired-samples T test). No abnormal ureteral dilatation was measured on ultrasound at the time of UTI or after infection recovery. The time distance between the rst and second measurements was 12.4 ± 1.5 days (mean ± SD). Age was not associated with the APD at the time of infection (Spearman rank correlation analysis, P = 0.307). The raw data are shown in Table 1.
In the UVJO with febrile UTI group, the APD was 19.3 ± 8.5 mm at the time of UTI and 15.2 ± 7.7 mm 1 week after infection recovery (P < 0.001) (paired-samples T test). The ureteric diameter was 11.0 ± 3.2 mm during urinary tract infection and 6.8 ± 2.6 mm 1 week after infection recovery (P < 0.001). The time distance between the rst and second measurements was 12.2 ± 1.5 days (mean ± SD). Age was not associated with the APD or ureteric diameter at the time of infection (Spearman rank correlation analysis, P = 0.382, P = 0.271). The raw data are shown in Table 2.
The paired sample T-test results of the rst and second ultrasonic measurements are summarized in Table 3.

Discussion
One animal experiment suggested that ureteral contraction could be reversibly inhibited by bacteria in the ureteral lumen(6). Moreover, 55-70% of spontaneous rhythmic contractions in sheep ureters were inhibited by the addition of small amounts of growth supernatants from E. coli, Pseudomonas aeruginosa and Klebsiella pneumoniae (13). In our observation, in the case of UVJO combined with febrile UTIs, the degree of ureteral dilatation and the APD during UTI were both higher than the values one week after infection recovery. Ureteropelvic dilatation was relieved after the infection was cured. Similar results were observed in clinical patients and in animal experiments.
Another animal study demonstrated that the combination of infection and obstructive hydronephrosis caused renal pelvic pressure elevation that was higher than that associated with either infection or obstructive hydronephrosis alone (7). In our observation, in the case of UPJO combined with febrile UTIs, the degree of APD during UTI was higher than the values one week after infection recovery. The effect of UTI on the aggravation of hydronephrosis due to UPJO has been demonstrated in clinical patients. However, in the case of UPJO, only the in uence of infection on the APD was observed, while the ureter, which was not originally dilated, did not expand under the in uence of infection.
There are studies on the mechanism of UTI affecting the upper urinary tract. Flagella and agellummediated motility/chemotaxis contribute to the tness of uropathogenic E. coli and therefore signi cantly enhance the pathogenesis of UTIs caused by uropathogenic E. coli (14). E. coli impair ureteric contractility in a Ca-dependent manner, largely caused by the stimulation of potassium channels, and this mechanism is dependent on host-urothelium interactions (15). The second messenger Ca 2+ activates the Ca 2+ /calmodulin-dependent myosin light chain kinase-dependent phosphorylation of 20-kDa regulatory light chains of myosin, which leads to ureteric contraction. In ammatory factors can initiate spontaneous activity in the proximal and distal ureter(16).
Many animal experiments and mechanisms of infection inhibiting ureteral peristalsis and causing urinary tract dilatation have been studied. The novelty of this study is that urinary tract expansion of UPJO or UVJO patients complicated by febrile UTIs was found to be lower after the infection was cured than during the infection. The clinical signi cance is described below.
When UPJO or UVJO leads to dilatation of the upper urinary tract, some patients may heal spontaneously, while others may require surgery. One of the surgical indications is a progressive increase in upper urinary tract hydronephrosis during follow-up(2). Febrile UTI is unpleasant but can be quickly controlled with accurate diagnosis and timely treatment. In patients with febrile UTIs, the dilatation of the upper urinary tract was reduced after antibacterial treatment. Therefore, if febrile UTI is present, the in uence of UTI should be taken into account in the evaluation of the degree of upper urinary tract dilation to make a more comprehensive surgical decision.
It would be even better to obtain ultrasound values of hydronephrosis within a short period of time (e.g., 1 week) before febrile UTI. We can analyze the dynamic changes in ultrasound results before, during, and after febrile urinary tract infection. However, it is impossible to precisely predict, in advance, which patients will develop febrile UTI. This is clinically challenging. In addition, this was a single-center retrospective study, and the number of single-center cases was not large. If prospective studies can be conducted to obtain the degree of upper urinary tract dilation before, during, and after infection recovery and to obtain more cases, the in uence of urinary tract infection on upper urinary tract dilation will be further clari ed.