Relationship among vesicoureteral reflux, urinary tract infection and renal damage in children

PURPOSE: We studied the relationship among vesicoureteral reflux, urinary tract infection and permanent renal damage in children. MATERIALS AND METHODS: We retrospectively analyzed 303 children younger than 2 years with a first time, nonobstructive, culture verified urinary tract infection. The protocol included ultrasonography and voiding cystourethrography within 3 months after urinary tract infection, and (99m)technetium dimercapto-succinic acid scintigraphy after 1 to 2 years. RESULTS: Vesicoureteral reflux was found in 36 of 163 boys (22%) and in 44 of 140 girls (31%). Of the 303 patients 80 (26%) had permanent renal damage according to dimercapto-succinic acid scintigraphy. The rate of abnormality increased significantly with grade of vesicoureteral reflux in boys and girls. The relative risk of renal damage was significantly increased in patients with vesicoureteral reflux grade II and higher. Maximum C-reactive protein concentration, maximum temperature during urinary tract infection, presence of vesicoureteral reflux and febrile recurrences of urinary tract infection were significantly related to permanent renal damage. In stepwise logistic regression vesicoureteral reflux was the only independent variable for boys, while C-reactive protein and vesicoureteral reflux were independent factors for girls. CONCLUSIONS: There was a significant relationship between grade II vesicoureteral reflux and higher and permanent renal damage in boys and girls. However, while the association between renal damage and vesicoureteral reflux was evident in boys, the role of urinary tract infection and renal inflammation seemed to be equally or more important in girls. These findings support the concept that renal damage is associated with vesicoureteral reflux and is often congenital in boys, while in girls it is more related to urinary tract infection with vesicoureteral reflux as a reinforcing factor.     

A multivariate analysis of dysfunctional elimination syndrome, and its relationships with gender, urinary tract infection and vesicoureteral reflux in children

PURPOSE: We explored and quantified the relationships between dysfunctional elimination syndrome (DES), and gender, urinary tract infection (UTI) and vesicoureteral reflux (VUR) in children. MATERIALS AND METHODS: Data on 2,759 pediatric patients treated at a referral practice who underwent renal sonography and voiding cystourethrography were summarized. The patients were children with VUR or normal genitourinary anatomy who presented with UTI or dysfunctional voiding and children screened for genitourinary problems such as hematuria, sibling reflux or bedwetting. A multivariate logistic regression approach was used to model and quantify the associations between DES and other pediatric urology factors. RESULTS: Of the girls 36.0% with unilateral VUR had DES, while 36.1% with bilateral VUR had DES. The corresponding rates for boys were 20.5% and 21.2%. The higher rate of DES in girls was independent of UTI and VUR status. While UTI was not associated with DES in boys or girls without VUR, in patients with VUR and UTI the risk of DES almost doubled (OR 1.97). Reflux alone without UTI was negatively associated with DES in boys (OR 0.50, 95% CI 0.34, 0.73) and girls (OR 0.26, 95% CI 0.19, 0.36). CONCLUSIONS: Girls had a significantly higher rate of DES than boys in all UTI and VUR subgroups in the current data. UTI significantly impacts the DES occurrence in patients with VUR. No statistically significant difference was detected in the DES rate between the unilateral and bilateral VUR groups, and the reflux group as a whole did not seem to have a higher rate of DES in boys or girls.     

Cessation of prophylactic antibiotics for managing persistent vesicoureteral reflux

PURPOSE: We reviewed our experience with patients with vesicoureteral reflux treated off prophylactic antibiotics. MATERIALS AND METHODS: We retrospectively reviewed the records of patients with vesicoureteral reflux treated off prophylactic antibiotics, noting the intervals on and off antibiotics, urinary tract infection, signs and symptoms associated with urinary tract infection, and renal ultrasound and dimercapto-succinic acid scan findings. RESULTS: We identified 196 patients with vesicoureteral reflux treated off prophylactic antibiotics, including 122 who were infection-free while on and 124 who had no urinary tract infection while off prophylactic antibiotics. The infection rate on and off prophylactics was 0.29 and 0.24 urinary tract infections per patient per year, respectively. New scars were identified in 5 patients while on prophylactics and in 7 after antibiotics were discontinued. Comparing different subgroups off prophylactic antibiotics showed that children who presented with scarring had statistically fewer new scars than those with normal initial dimercapto-succinic acid imaging (p <0.043). Girls had significantly more urinary tract infections than boys while off prophylactics (p <0.01) despite the older age at antibiotic cessation. However, after infection occurred while off prophylactic antibiotics, new renal scars developed at about the same rate in boys and girls. Because most patients did not have a urinary tract infection while off prophylactic antibiotics, new renal scars developed in only 2.2% of all boys and 4% of all girls. CONCLUSIONS: Our findings imply that discontinuing antibiotics is reasonable and safe in patients in whom vesicoureteral reflux fails to resolve.     

Vesicoureteral reflux in the Hispanic child with urinary tract infection

PURPOSE: Hispanic individuals have become the largest minority in the United States. Prior studies of minorities revealed real differences in vesicouretal reflux rates between white and black Americans. We studied the incidence of reflux in the Hispanic population to see if the reflux rate was different from that of the white population. MATERIALS AND METHODS: We reviewed the results of voiding cystourethrograms performed in Hispanic children as our normal screening for reflux and compared them to voiding cystourethrograms results in a group of white children. The children were identified as Hispanic or white by their parents on an intake form. RESULTS: Of the Hispanic children 27% had vesicoureteral reflux on voiding cystogram, while 32% of the white children had vesicoureteral reflux. CONCLUSIONS: Hispanic patients presenting with the first urinary tract infection seem to be afflicted with vesicoureteral reflux as often as their white contemporaries. Hispanic children should be screened as aggressively as white children when they present with urinary tract infections.     

Long-term followup of 158 young adults surgically treated for vesicoureteral reflux in childhood: the ongoing risk of urinary tract infections

PURPOSE: We recorded urinary tract infections in the long term after surgical reflux correction. MATERIALS AND METHODS: A total of 158 of 189 patients (160 females and 29 males) who were followed in 1985, an average of 10.8 years after reflux surgery were contacted again in 1995. At that time median patient age was 26 years (range 15.7 to 38.8) and the average period of observation was 20.3 years (range 13.4 to 26). RESULTS: In 82% of the patients febrile and in 18% afebrile symptomatic urinary tract infections had developed preoperatively. In the first 10-year period after operation 46% of patients continued to have symptomatic urinary tract infections compared with 52% in the second 10-year interval. In the 2 periods the incidence of febrile urinary tract infection was about 17%. In the whole postoperative observation period symptomatic urinary tract infections developed in 66% of all patients, including 74% of female patients. Symptomatic urinary tract infections were observed during 8 of 46 pregnancies (17%). CONCLUSIONS: After successful surgical reflux correction susceptibility to urinary tract infection continues for a number of years in many girls and women. However, postoperatively urinary tract infections are primarily afebrile.     

Changing concepts concerning the management of vesicoureteral reflux

PURPOSE: Conservative estimates indicate that up to 54% of patients who present with vesicoureteral reflux have dysfunction voiding. Children with voiding dysfunction and vesicoureteral reflux historically have a high breakthrough infection rate of 34% to 43%. Breakthrough infection represents significant morbidity and it is the most common indication for surgical intervention for vesicoureteral reflux. Voiding dysfunction is present in 79% of patients who proceed to reflux surgery. We evaluated the impact of pelvic floor muscle retraining combined with a medical program in patients with voiding dysfunction and vesicoureteral reflux. MATERIALS AND METHODS: Children with a history consistent with voiding dysfunction and vesicoureteral reflux were screened by uroflowmetry/electromyography, bladder scan for post-void residual urine, renal ultrasound and voiding cystourethrography. Confirmed cases of voiding dysfunction and vesicoureteral reflux were prospectively enrolled in this study. Children participated in an interactive, computer assisted, pelvic floor muscle retraining program that involved a conservative medical regimen and pelvic floor muscle retraining. All patients received prophylactic antibiotics. We evaluated the rate of breakthrough urinary tract infection, reflux outcome and surgical intervention. A literature review with the key words vesicoureteral reflux, voiding dysfunction and urinary tract infection was performed to identify historical control cases for comparison. RESULTS: Study enrollment criteria were fulfilled by 49 girls and 4 boys 4 to 13 years old (average age 8.8), representing 72 units with low grades I to II (48) and high grades III to V (24) reflux. Mean followup was 24 months. Initial uroflowmetry/electromyography and bladder scan revealed a staccato flow pattern and normal post-void residual urine in 11% of cases, staccato flow pattern and elevated post-void residual urine in 10%, flattened flow pattern and normal post-void residual urine in 28%, and flattened flow pattern and elevated post-void residual urine in 51%. Breakthrough infection developed in 5 patients (10%), including 1 in whom reflux had resolved and 1 with grade I reflux who underwent observation. The parents of 2 patients elected to complete biofeedback without surgical intervention and these patients did not have a repeat infection. Reimplantation was performed in 1 case (2%). There was resolution in 18 low and 7 high grade refluxing units, including 2 older patients with a long history of high grade bilateral disease. Average time to resolution was 7.8 months. We noted elevated post-void residual urine in 88% of the patients with high grade reflux. Average age at resolution was 9.2 years. During a 24-month period one of us (P. H. M.) noted a greater than 90% decrease in surgical intervention. CONCLUSIONS: A combined conservative medical and computer game assisted pelvic floor muscle retraining program appears to have decreased the incidence of breakthrough urinary tract infections and facilitated reflux resolution in children with voiding dysfunction and vesicoureteral reflux. Patients with high grade reflux and voiding dysfunction commonly present with elevated post-void residual urine, contraindicating the indiscriminate administration of anticholinergics. Decreasing the rate of urinary tract infections may have a dramatic impact on the need for surgical intervention and enable the reflux resolution rate to approximate that in patients without voiding dysfunction. Prospective controlled trials are needed to determine whether pelvic floor muscle retraining combined with a conservative medical regimen alters the natural history of vesicoureteral reflux in patients with voiding dysfunction.     

Epidemiology and risk factors for urinary tract infection in patients with spinal cord injury

PURPOSE: To our knowledge risk factors for urinary tract infection associated with various drainage methods in patients with spinal cord injury have never been evaluated overall in the acute period. We identified the incidence and risk factors associated with urinary tract infection in spinal cord injured patients. MATERIALS AND METHODS: We prospectively followed 128 patients at our spinal cord injury reference hospital for 38 months and obtained certain data, including demographic characteristics, associated factors, methods of urinary drainage, bladder type, urological complications and predisposing factors of each infection episode. Logistic regression modeling was done to analyze variables and identify risk factors that predicted urinary tract infection. RESULTS: Of 128 patients 100 (78%) were male with a mean age plus or minus standard deviation of 32 +/- 14.52 years. All patients had a nonfatal condition by McCabe and Jackson guidelines, and 47% presented with associated factors. The incidence of urinary tract infection was expressed as number episodes per 100 patients daily or person-days. The overall incidence of urinary tract infection was 0.68, while for male indwelling, clean intermittent, condom and female suprapubic catheterization, and normal voiding the rate was 2.72, 0.41, 0.36, 0. 34 and 0.06, respectively. The risk factors associated with urinary tract infection were invasive procedures without antibiotic prophylaxis, cervical injury and chronic catheterization (odds ratio 2.62, 3 and 4, respectively). Risk factors associated with repeat infection were a functional independence measure score of less than 74 and vesicoureteral reflux (odds ratio 10 and 23, respectively). CONCLUSIONS: Spinal cord injured patients with complete dependence and vesicoureteral reflux are at highest risk for urinary tract infection.     

Dimercapto-succinic acid scintigraphy instead of voiding cystourethrography for infants with urinary tract infection

PURPOSE: We study the ability of dimercapto-succinic acid (DMSA) scintigraphy to predict the presence of dilating vesicoureteral reflux (VUR) in infants with urinary tract infection (UTI) to simplify the evaluation protocol. MATERIALS AND METHODS: A retrospective analysis of the records of 303 children younger than 2 years with initial UTI investigated with DMSA scintigraphy and voiding cystourethrography (VCU) within 3 months after UTI was performed. RESULTS: In 156 of the 303 children (51%) DMSA scintigraphy showed renal lesions. VUR was found in 80 patients (26%) and VUR grade significantly correlated with the presence of renal lesions. A normal DMSA scintigraphy and dilating VUR (grade III) occurred in 7 infants. At followup after 1 to 2 years, 6 of these 7 patients had normal DMSA scans and 1 had a scarred duplex kidney. VUR resolved spontaneously in 5 and improved spontaneously to grade 1 in 2 patients. None of the 7 children had recurrent UTI. CONCLUSIONS: DMSA scintigraphy in infants with UTI may replace VCU as a first line investigation. A strategy to perform VCU in only patients with renal lesions is proposed. In this study 147 of 303 VCUs would have been unnecessary as only 1 child with a damaged kidney was missed.     

Spontaneous resolution of vesicoureteral reflux: a 15-year perspective

PURPOSE: The spontaneous resolution rate of vesicoureteral reflux is helpful for determining the need for surgical intervention and the proper followup schedule in patients on antibiotic prophylaxis. We determined the resolution rate by patient rather than by ureter and analyzed the effects of laterality, gender, age and dysfunctional voiding. MATERIALS AND METHODS: We retrospectively reviewed the records of 179 girls and 35 boys who presented between 1981 and 1984 with urinary tract infection and were diagnosed with primary vesicoureteral reflux. Mean age at presentation was 4.2 years and median followup was 3 years. Of the patients 107 (50%) had bilateral reflux and 60 had dysfunctional voiding. In 146 children (68%) reflux spontaneously resolved during the study. Patients were categorized by the worst grade of reflux, maintained on antibiotic prophylaxis and underwent voiding cystourethrography yearly until reflux resolved. Kaplan-Meier curves were constructed to define the resolution rate. RESULTS: Grades I to III reflux resolved at 13% yearly during the initial 5 years of followup and then at 3.5% yearly during subsequent followup. Grade IV to V reflux resolved at 5% rate yearly. Bilateral reflux resolved more slowly than unilateral reflux and it resolved more rapidly in boys than in girls. Untreated dysfunctional voiding had no effect on overall resolution. CONCLUSIONS: Grades I to III primary vesicoureteral reflux diagnosed after urinary tract infection resolve at identical rates and significantly more rapidly than grades IV to V. Early repair of grade IV to V reflux should be considered after age 18 months.     

Spontaneous resolution of high grade infantile vesicoureteral reflux

PURPOSE: We studied the spontaneous resolution rate in a group of infants with high grade vesicoureteral reflux (VUR). The influence of gender, prenatal or postnatal diagnosis, recurrent urinary tract infections (UTIs) and bladder dysfunction on the resolution rate was also evaluated. MATERIALS AND METHODS: This prospective study comprised 115 infants (80 boys and 35 girls) with high grade VUR (grades III to V). Bilateral reflux was seen in 70% of cases. The majority of patients (71%) were diagnosed after UTI during infancy and only 26% were prenatally diagnosed. Median age at diagnosis was 2.7 months. Patients were followed according to a program of repeat video cystometry and noninvasive 4-hour voiding observations. Median followup was 39 months. RESULTS: The overall spontaneous resolution rate to grade II or less for all grades was 39% with no difference between boys and girls. However, when comparing the more severe grades IV and V, we found a significantly higher resolution rate in boys during the infant year. No difference in VUR disappearance could be detected when comparing the groups according to presentation, prenatal ultrasound or pyelonephritis. Breakthrough UTIs were seen in 47% of cases despite antibacterial prophylaxis and they significantly correlated with VUR nonresolution. Bladder dysfunction was found in 37% of patients and it also significantly correlated with nonresolution. CONCLUSIONS: The spontaneous resolution rate for high grade (grades IV and V) congenital VUR was high in boys during the infant year (29%), whereas in girls and boys after the infant year the resolution rate was 9% yearly during followup. Negative prognostic factors for resolution were recurrent UTIs and bladder dysfunction.     

Effective postcoital prophylaxis of recurrent urinary tract infections in premenopausal women: A review

A total of 77 sexually active premenopausal women, susceptible to recurrent urinary tract infections (UTI) but otherwise healthy, were subjected to postcoital prophylaxis consisting of a single oral dose of either cotrimoxazole (80 mg trimethoprim+400 mg sulfamethoxazole), 50 mg nitrofurantoin macrocrystals, 500 mg nalidixic acid, 250 mg cinoxacin or 250 mg cephalexin. Postcoital prophylaxis reduced the incidence of recurrent UTI from 5-8 UTI per patient/year prior to prophylaxis, to a mere 0.03 UTI per patient/ year following prophylaxis. The differences in the incidence of UTI prior to and following institution of postcoital prophylaxis were statistically highly significant. A mean of 106–120 antibacterial tablets per patient were administered per year.Postcoital prophylaxis of recurrent UTI in premenopausal women is highly effective because of easy compliance, the high urinary concentration achieved and the minimal induction of resistance in the introital Gram-negative bacterial flora, irrespective of the length of time this prophylaxis is used. Furthermore, postcoital prophylaxis is significantly more effective than daily, as it achieves the same effect but requires only one third or fewer of the antibacterial tablets used in daily prophylaxis. At present, postcoital prophylaxis with cotrimoxazole, nitrofurantoin macrocrystals or cephalexin is recommended.     

Renal and bladder functional status at diagnosis as predictive factors for the outcome of primary vesicoureteral reflux in children

PURPOSE: We studied the relationship between renal and bladder functional status at diagnosis and spontaneous resolution of reflux in young children with primary vesicoureteral reflux. MATERIALS AND METHODS: Children with grade III or greater vesicoureteral reflux were recruited for the study. At entry each patient underwent voiding cystourethrogram, renal ultrasound, isotope renogram, and natural filling and conventional filling urodynamic studies. Patients were then divided into 4 groups-group 1 had normal renal and bladder function, group 2 had abnormal renal and normal bladder function, group 3 had normal renal and abnormal bladder function, and group 4 had abnormal renal and bladder function. Correlation between renal and bladder functional status with reflux resolution at a minimum followup of 24 months was evaluated. RESULTS: A total of 82 patients (mean age 3.8 years) were prospectively evaluated and followed. There were 18 patients (13 males and 5 females) in group 1, 19 (13 and 6) in group 2, 19 (18 and 1) in group 3 and 26 (22 and 4) in group 4. Complete resolution of vesicoureteral reflux occurred in 17 patients (94%) in group 1 and 7 (37%) in group 2. None of the patients from group 3 or group 4 achieved complete vesicoureteral reflux resolution. Reflux grade remained unchanged in 15 patients (79%) in group 3 and 20 (77%) in group 4. CONCLUSIONS: Resolution of vesicoureteral reflux significantly correlated with renal and bladder functional status at diagnosis. Normal renal and bladder function at diagnosis is highly predictive of complete resolution of vesicoureteral reflux, whereas abnormal renal and bladder function is prognostic for persistence of reflux.     

Survey results on medical and surgical followup of patients with vesicoureteral reflux from American Association of Pediatrics, Section on Urology members

PURPOSE: Little data are available on the appropriate followup protocols for patients treated medically or surgically for vesicoureteral reflux. We surveyed urologists who primarily practice pediatric urology to determine current practice patterns for following patients treated for vesicoureteral reflux. MATERIALS AND METHODS: A 1-page survey was mailed to the 225 members of the American Academy of Pediatrics, Section on Urology. The mailing roster and labels were provided by the American Academy of Pediatrics. The survey included questions on the followup of patients with low and high grade reflux treated medically or surgically. Returned surveys were blindly tabulated by 2 independent reviewers (F. A. F. and P. H. M.). RESULTS: Of the 225 surveys 155 were returned and analyzed for an overall response rate of approximately 61%. Urine culture is routinely performed by 64% and 71% of respondents to follow children with uncorrected low grade reflux and those with high grade reflux undergoing medical treatment, respectively, generally at 3 to 6-month intervals. To follow patients with reflux voiding cystourethrography or radionuclide scan is performed yearly by 99% of study participants, while 77% perform ultrasound. Renal scan and excretory urography are done infrequently. The timing of the surgical correction of unresolved asymptomatic reflux and/or when to discontinue antibiotics in these cases varied significantly among survey respondents. After antireflux surgery 92% and 91% of respondents perform voiding cystourethrography and ultrasound, respectively. Recommended followup after ureteroneocystotomy varied greatly among survey participants. CONCLUSIONS: The overwhelming majority of practitioners agree on the timing and type of radiographic studies to be used to follow children treated for reflux and the majority routinely perform urine culture. Opinion on the continuation of antibiotics and timing of surgical intervention for asymptomatic unresolved reflux is divided. Wide variation exists on the recommended followup after reimplantation.     

The use of intravesical hyaluronic acid for recurrent urinary tract infections in children: a case-series study

Abstract

Background: This is the first study performed to evaluate the effects of intravesical hyaluronic acid (IHA) instillation on diminishing the frequency of recurrent urinary tract infections (UTIs) in children. Methods: Fifteen children (10 girls, 5 boys) with recurrent UTIs were divided into two groups as either complicated (group 1) (with accompanying disorders including vesicoureteral reflux or neurogenic bladder) or uncomplicated patients (group 2). After administration of weekly four sessions of IHA therapy the patients were followed-up monthly for 2 years and classified as responsive (complete/partial) or unresponsive to treatment. Results: 53.3% of the patients with recurrent UTIs were complicated. In group 1 (n?=?8), complete and partial response rates were 62.5% (n?=?5) and 25% (n?=?2), respectively. There was no response in 12.5% (n?=?1) of the cases in group 1. In group 2 (n?=?7), complete and partial response rates were 71.4% (n?=?5) and 14.3% (n?=?1), respectively. In this group, 14.3% (n?=?1) of the patients were found to be unresponsive to IHA treatment. No side effects were observed in any of the patients. Conclusions: IHA administration is considered as an effective treatment modality which significantly reduces the prevalence of or even provides complete recovery from recurrent UTIs in childhood. Therefore, it is believed that this approach can be used as a promising alternative to widespread use of antibiotics in this patient group.