Role of Bladder Dysfunction in Vesicoureteral Reflux

Lower urinary tract dysfunction (LUTD) is associated with vesicoureteral reflux (VUR) as well as urinary tract infections (UTIs), particularly when micturition abnormalities occur in the voiding phase. The most common presenting symptoms are urinary urgency and frequency, UTI, incontinence, holding behaviors, and dysuria; many children will also have concurrent constipation. Since LUTD is associated with lower VUR resolution rates, increased rates of breakthrough UTI, and increased rates of surgical treatment failure, successful management of VUR in the setting of LUTD requires therapy for the VUR as well as concomitant management of the LUTD to maximize treatment success. LUTD treatment should be applied sequentially, beginning with behavioral modification and progressing to pharmacologic agents, biofeedback, and neuromodulation in refractory patients.     

Risk factors of vesicoureteral reflux and urinary tract infections in children with imperforate anus: A population-based case-control study in Taiwan

Imperforate anus (IA) is associated with several urological anomalies, including vesicoureteral reflux (VUR), a major contributor to high morbidity in patients with anorectal malformations. This retrospective study was performed to elucidate the risk factors of vesicoureteral reflux (VUR) and UTI in children with IA.We used the National Health Insurance Research Database (NHIRD) to estimate the frequency of congenital anomalies of the kidney and urinary tract (CAKUT) in children with IA. We also investigated the frequencies of VUR, UTI, and CAKUT in children with IA along with the risk factors of VUR.We enrolled 613 children between 2000 and 2008 (367 males and 246 females; 489 low-position IA and 124 high-position IA). High-position IA was associated with a significantly increased risk of VUR compared with low-position IA (OR: 2.68, 95% CI: 1.61, 4.45). In addition, children with IA along with CAKUT, hydronephrosis, or UTI had a higher risk of VUR (OR: 8.57, 95% CI: 3.75, 19.6; OR: 7.65, 95% CI: 4.48, 13.1; and OR: 31.8, 95% CI: 11.5, 88.3, respectively). UTI, as well as chromosomal anomalies, were more frequent in children with high-position IA.Patients with a high-position IA had a greater risk of VUR, particularly those with CAKUT, hydronephrosis, or UTI. Such patients must periodically undergo urinalysis to screen for UTI and early voiding cystourethrogram to rule out VUR and prevent consequent renal damage. Chromosomal analysis is suggested to rule out Down syndrome.     

Antibiotics or surgery for vesicoureteric reflux in children

CONTEXT: 1-2% of children have vesicoureteric reflux (VUR). VUR occurs in 25-40% of children with acute pyelonephritis. VUR can lead to renal scarring, hypertension, and end-stage renal disease. The best form of treatment for children with VUR is debated: no treatment, long-term antibiotic prophylaxis, surgery, or a combination of antibiotic prophylaxis and surgery. In children with recurrent urinary tract infections (UTIs) and progressive renal damage, despite antibiotic prophylaxis, surgical correction of VUR, especially high-grade VUR, is generally recommended. STARTING POINT: Danielle Wheeler and colleagues recently did a meta-analysis of ten randomised controlled trials (964 children) to evaluate whether any intervention for VUR is better than no treatment (Cochrane Database Syst Rev 2004; 3: CD001532). The main endpoints were incidence of UTIs, new or progressive renal damage, renal growth, hypertension, and glomerular filtration rate. They concluded that it is uncertain whether the identification of children with VUR is associated with clinically important benefit. The additional benefit of surgery over antibiotics is small. WHERE NEXT? New strategies for management will require a tailored diagnostic and therapeutic approach, including non-invasive or less invasive diagnostic procedures, and a less aggressive therapeutic approach. Whether the common practice of cystourethrography as a first-line investigation is warranted needs evaluation. The goal of paediatricians in the future, to prevent kidney damage, will probably be prevention of renal parenchymal injury and not necessarily the correction of ureterovesical junction anomalies. Because two main clinical pictures of VUR (diagnosed prenatally or postnatally with different age and sex distribution) can be identified, boys and girls will probably be managed differently. The factors responsible for congenital and acquired renal injury in children with VUR need to be studied.     

Long-term follow-up of children with vesicoureteral reflux with and without antibiotic prophylaxis

The aim of the present study was to obtain data on the outcome of children with persistent vesicoureteral reflux (VUR) after cessation of antibiotic prophylaxis. Children with VUR who had been on antibiotic prophylaxis for at least 2 y and were free of urinary tract infections (UTI), had normal voiding patterns, and no hydronephrosis or new kidney scarring, had antibiotic prophylaxis discontinued, were followed up prospectively with urine cultures, voiding cystourethrography, and technecium-99m dimercaptosuccinate renal scintigraphy. The findings were compared with those of the same patients while they were on antibiotic prophylaxis. In 54 children (39 girls and 15 boys), antibiotic prophylaxis was discontinued. The mean follow-up time on and off antibiotic prophylaxis was 4.4+/-2.1 and 4.4+/-2.2 y, respectively. Nine UTI episodes occurred during the on- and 8 during the off-prophylaxis period. In 80 of 96 and in 68 of 74 ureters the reflux resolved or downgraded during the on- and off-prophylaxis periods, respectively. No new scar lesions were detected in any of the children. In conclusion, in children with persistent VUR and certain characteristics, antibiotic prophylaxis can be safely discontinued.     

Renal Scarring in the Randomized Intervention for Children with Vesicoureteral Reflux (RIVUR) Trial

Background and objectives

The main objectives of the Randomized Intervention for Children with Vesicoureteral Reflux (RIVUR) trial were to evaluate the role of antimicrobial prophylaxis in the prevention of recurrent urinary tract infection (UTI) and renal scarring in children with vesicoureteral reflux (VUR). We present a comprehensive evaluation of renal scarring outcomes in RIVUR trial participants.

Design, setting, participants, & measurements

This multicenter, randomized, placebo-controlled trial enrolled 607 children aged 2–71 months with grade 1–4 VUR diagnosed after a first or second febrile or symptomatic UTI. Study participants received trimethoprim-sulfamethoxazole or placebo and were followed for 2 years. Renal scarring was evaluated by baseline and follow-up ^99mtechnetium dimercaptosuccinic acid (DMSA) renal scans that were reviewed independently by two blinded reference radiologists.

Results

At the end of the study, 58 (10%) of 599 children and 63 (5%) of 1197 renal units had renal scarring. New renal scarring did not differ between the prophylaxis and placebo groups (6% versus 7%, respectively). Children with renal scarring were significantly older (median age, 26 versus 11 months; P=0.01), had a second UTI before enrollment (odds ratio [OR], 2.85; 95% confidence interval [95% CI], 1.38 to 5.92), were more likely to be Hispanic (OR, 2.22; 95% CI, 1.13 to 4.34), and had higher grades of VUR (OR, 2.79; 95% CI, 1.56 to 5.0). The proportion of new scars in renal units with grade 4 VUR was significantly higher than in units with no VUR (OR, 24.2; 95% CI, 6.4 to 91.2).

Conclusions

Significantly more renal scarring was seen in relatively older children and in those with a second episode of febrile or symptomatic UTI before randomization. Preexisting and new renal scars occurred significantly more in renal units with grade 4 VUR than in those with low-grade or no VUR. Antimicrobial prophylaxis did not decrease the risk of renal scarring.     

Genetics of vesicoureteral reflux

Primary vesicoureteral reflux (VUR) is the most common urological anomaly in children, affecting 1-2% of the pediatric population and 30-40% of children presenting with urinary tract infections (UTIs). Reflux-associated nephropathy is a major cause of childhood hypertension and chronic renal failure. The hereditary and familial nature of VUR is well recognized and several studies have reported that siblings of children with VUR have a higher incidence of reflux than the general pediatric population. Familial clustering of VUR implies that genetic factors have an important role in its pathogenesis, but no single major locus or gene for VUR has yet been identified and most researchers now acknowledge that VUR is genetically heterogeneous. Improvements in genome-scan techniques and continuously increasing knowledge of the genetic basis of VUR should help us to further understand its pathogenesis.     

Reappraisal of the effectiveness of 99mTc-dimercaptosuccinic acid scans for selective voiding cystourethrography in children with a first febrile urinary tract infection

Recent studies have yielded conflicting results regarding the ability of technetium-99m dimercaptosuccinic acid (^99mTc-DMSA) renal scans for identifying high-grade vesicoureteral reflux (VUR) in children with a first febrile urinary tract infection (UTI). This study aimed to reevaluate the effectiveness of ^99mTc-DMSA renal scans for selective voiding cystourethrography (VCUG) in children with a first febrile UTI. The medical records of children aged ≤ 5 years who were admitted with a first febrile UTI were retrospectively reviewed. Ultrasonography (US) and DMSA renal scans were performed within 3–5 days after admission, and VCUG was performed 7–10 days after antibiotics treatment. A total of 653 children were enrolled for analysis, including 579 patients aged < 2 years (Group A) and 74 patients aged 2–5 years (Group B). In Group A, DMSA scans were abnormal for 346 patients (59.8%), and normal for 233 patients (40.2%). High-grade VUR was present in 99 of 346 patients (28.9%) with abnormal DMSA scans, but present in only 16 of 233 patients (6.9%) with normal DMSA scans (p < 0.001). Regarding the prediction of high-grade VUR, the sensitivity and negative predictive value (NPV) for the DMSA scans were 86.1% and 93.1%, respectively. In Group B, DMSA scans were abnormal for 36 patients (48.6%), and normal for 38 patients (51.4%). High-grade VUR was present in 12 of 36 patients (33.3%) with abnormal DMSA scans, whereas none of the 38 patients with normal DMSA scans had high-grade VUR (p < 0.001). The sensitivity and NPV of the DMSA scans were both 100%. Using the selective VCUG strategy, approximately 40% of Group A patients and 50% of Group B patients could be spared an unnecessary VCUG, respectively. Our study results suggest that ^99mTc-DMSA renal scans are effective in identifying children with a first febrile UTI for selective VCUG.     

Vesicoureteral reflux in children

Vesicoureteral reflux is a common disease in children and is usually associated with urinary tract infections and renal scars. Renal damage associated with vesicoureteral reflux occurs secondary to renal maldevelopment during fetal life or renal infections in children and may produce hypertension, diseases in pregnancy and chronic renal failure. Bladder dysfunction may be responsible for persistent reflux and renal scars. In order to prevent renal damage, early diagnosis and prompt medical treatment or surgical correction are advised in a selected group of children. In the past all children with urinary tract infections were investigated with voiding uretrocystogram and received long-term antibiotic prophylaxis or surgery. In recent years several trials have provided information that suggest it is better to reduce the number of diagnostic and surgical procedures in children affected by vesicoureteral reflux.     

The natural history of bacteriuria in childhood

The highest figure for first-time UTI is found in infants below one year of age. These early infections are often pyelonephritic in character, but they are easily overlooked because symptoms are unspecific, high fever and failure to thrive being the most important. It has been shown that delay in start of treatment increases the risk of the child developing pyelonephritic scarring. There is reason to believe that undetected and therefore untreated attacks of pyelonephritis may be associated with renal scarring revealed later in life. This type of renal damage is associated with development of hypertension in about 10 per cent of children and it accounts for around 20 per cent of the children entered into dialysis and transplant programs. Prevention of such long-term problems would be of great value and pyelonephritic scarring is a potentially preventable disease. The majority of infants and young children with UTI are probably managed at the primary care level. It is therefore essential that general practitioners are well informed about the epidemiology of UTI in infancy and childhood and that adequate diagnostic facilities are provided. For example, suprapubic aspiration to obtain uncontaminated urine is a technique that may well be used in an outpatient setting, and dipslide cultures are accurate and inexpensive. In addition to young age, vesicoureteric reflux and repeated attacks of pyelonephritis are risk factors associated with development of renal scarring. Therefore, diagnostic imaging to detect children with anomalies within the urinary tract are especially important in the very young. Furthermore, long-term supervision should be provided and the parents advised to consult the doctor when there is suspicion of a new infection to avoid delay in treatment. There is no reason to perform general screening for bacteriuria in healthy infants. Although bacteriuria may be found in 1 to 2 per cent, asymptomatic children have a very high rate of spontaneous clearing of the bacteriuria and they seem to constitute a low-risk group. Instead, frequent culturing of urine from febrile infants would be much more important.     

Vesicoureteral reflux in adults

Vesicoureteral reflux (VUR) may be congenital or acquired. The most frequent form of congenital VUR is primary VUR. Its prevalence in adults is not exactly known, but it is higher in women, whose greater propensity for urinary tract infections increases the likelihood of an instrumental examination leading to the diagnosis of less severe cases. In men, even severe VUR may go undiagnosed for a long time. Primary VUR is due to a defect in the valve mechanism of the ureterovesical junction. In physiological conditions, the terminal ureter enters the bladder wall obliquely and bladder contraction leads to compression of this intravesical portion. Abnormal length of the intravesical portion of the ureter due to a genetic mutation (whose location is yet to be established) leads to VUR. In its less severe forms VUR may be asymptomatic, but in 50-70% of cases it manifests with recurrent cystitis or pyelonephritis. The manifestations leading to a diagnosis of VUR in adults, besides urinary tract infections, are proteinuria, renal failure and hypertension. The gold-standard diagnostic examination is a micturating cystourethrogram. Reflux nephropathy develops as a result of a pathogenetic mechanism unrelated to high cavity pressure or urinary tract infections but due to reduced formation of the normal renal parenchyma (hypoplasia or dysplasia). Abnormal renal parenchyma development is attributable to the same genes that control the development of the ureters and ureterovesical junction. VUR is considered only a marker of this abnormal development, playing no role in scar formation. There is no conclusive evidence regarding the indications for VUR correction. However, the risk that VUR leads to recurrent pyelonephritis and reflux nephropathy must be kept in mind. VUR certainly has to be corrected in women who contemplate pregnancy.     

Urinary tract infection in childhood

The urinary tract infection (UTI) is one of the major causes of bacterial infection in children. Therefore an opportune diagnosis, an adequate treatment and a close follow up will prevent chronic renal damage. In this brief article UTI clinical characteristics and recommendations for diagnosis and treatment according to children age are reviewed.     

Endoscopic and surgical treatment of vesico-ureteral reflux in children. Comparative long-term follow-up

PRINCIPLES: This retrospective study analyzes the long-term results of endoscopic and surgical treatment of vesico-ureteral reflux in children. METHODS: A cohort of 130 patients, 67 girls and 63 boys with a mean age of 30 months were treated either by endoscopic subureteral collagen injection (SCIN) in 92 and by Cohen reimplantation surgery in 123 refluxing ureteral units. Mean follow-up was 4.2 years varying from 1 to 8.7 years. Reflux recurrence, urinary tract infection (UTI) and renal function were evaluated. RESULTS: After SCIN reflux was absent in 64% at 6 months. 20% of the initially 92 refluxing ureters were injected twice. After one or two injections reflux was absent in 71%. In 21% recurrent reflux was of grade I or II, not requiring further treatment. UTI was observed in 27%. After Cohen ureteral reimplantation reflux was absent in 96% at 6 months. UTI was observed in 23%. Renal function at diagnosis and follow-up was compared in children with bilateral grade III reflux only. In patients treated with SCIN it was normal in 77% preoperatively and in 90% at follow-up. In patients treated by open surgery it was normal in 47% preoperatively and in 76% at follow-up. CONCLUSION: For high-grade vesico-ureteral reflux re-implantation surgery remains the gold standard. SCIN is indicated for low and medium grade reflux. Recurrent bacteriuria was observed more often after SCIN and pyelonephritis more often after open surgery. The renal function seems to be preserved with both techniques.     

Review of adolescent urinary tract infection

The diagnosis and management of adolescent urinary tract infection (UTI) shares some of the clinical features seen in infections of the young and old. Whereas most infections in the young patient demand an extensive radiologic work-up, the teenager with a UTI is not so straightforward. The clinical must balance being too aggressive with being too conservative in the diagnosis and management of these patients. UTIs occur most frequently among adolescent females and are usually uncomplicated and not associated with underlying anatomic abnormalities. Smaller numbers of adolescent males suffer from UTIs, and the need to search for underlying abnormalities is not clear. Adolescent UTI is associated with nascent sexual activity and is also more common in voiding/elimination syndromes. Future studies examining UTI, specifically in the adolescent age group, will help provide clinicians with a more focused algorithm in the diagnosis and management of adolescent UTIs.     

Detection of Vesicoureteric Reflux Using Radionuclide Micturating Cystography

Summary: Detection of vesicoureteric reflux using radionuclide micturating cystography. R. R. Bailey, Patricia Stapleton, J. G. Turner and B. E. W. Brownlie, Aust. N.Z. J. Med., 1976, 6, pp. 542–544.
Radionuclide micturating cystography (RMC) has been compared with the standard micturating cystourethrogram for detecting vesicoureteric reflux (VUR). Of 16 renal tracts with VUR radiologically classified as gross all had reflux demonstrated on RMC and in 15 of these the reflux reached the renal pelvis. Eight of the 12 renal tracts with moderate VUR and three of four with slight VUR were shown to reflux on RMC.
RMC should prove valuable for following the course of patients with VUR treated surgically or conservatively because of the lower gonadal radiation dose resulting from this technique compared with the conventional radiological method.     

Bilateral nephrectomy as a life saving procedure in a young woman with recurrent bacteremic shock

On the basis of the recurrent bacteremic shock in young woman with bilateral reflux nephropathy and recurrent urinary tract infections (UTI) from early childhood we present diagnostic and therapeutic problems of complicated UTI. Negative results of localization diagnosis of UTI and clinical suspicious on renal microabscesses as a cause of recurrence bacteremic shock were the reason of bilateral nephrectomy--as a life saving procedure--and initiation of CAPD programme.     

Using Tc-99m DMSA renal cortex scan to detect renal damage in women with type 2 diabetes

Women with diabetes mellitus (DM) have urinary tract infection (UTI) more often than women without DM. It is unknown, however, what the prevalence and type of renal damage due to UTI is in these women. Therefore, in this study, we compared type 2 DM women with or without UTI history for the prevalence and type of renal damage by technetium-99m dimercapto-succinic acid (Tc-99m DMSA) renal scan. A total of 128 type 2 DM women with or without UTI history received Tc-99m DMSA renal scan were included in this study. The patients were separated into three groups: (1) 43 patients without UTI history, (2) 42 patients with only lower UTI (cystitis) history and (3) 43 patients with upper UTI (pyelonephritis) history. The renal scan findings were separated into three types: (A) normal, (B) inflammation and (C) scar. The 31.9% (50/128) of type 2 DM patients had renal damages. Group 1 patients had a significantly lower prevalence of renal damages including inflammation and scar as compared to Groups 2 and 3 patients. In addition, the prevalence of renal damage was significantly higher in Group 3 than in Group 2 patients. Renal scars only were visualized in Group 3 patients. However, other clinical data were not statistically different among the three group patients. Type 2 DM women with UTI history, especially if they had upper UTI have a significantly higher prevalence of renal damage than in those without UTI.     

Urinary Excretion of β-Hexosaminidase in Patients with Vesico-Ureteric Reflux

ABSTRACT. Urinary excretion of β-hexosaminidase was studied in 50 patients with vesico-ureteric reflux (VUR) in order to obtain information on the renal injury in this disease. There was no correlation between urinary enzyme excretion and the degree of VUR. Patients without pyelonephritic changes and with normal serum creatinine values showed normal excretion of β-hexosaminidase. Patients with pyelonephritic changes but normal serum creatinine had enzyme activity towards the upper limit of the normal range whilst patients with pyelonephritic changes and decreased renal function (high serum creatinine) showed increased excretion of urinary β-hexosaminidase. Some of the patients with VUR and asymptomatic bacteriuria exhibited increased excretion of urinary β-hexosaminidase and six with acute pyelonephritis had very high levels. These findings indicate that the infective process plays an essential role, besides VUR, in the development of kidney damage.     

Pathogenesis of urinary tract infections with normal female anatomy

Recurrent urinary tract infections (UTIs) are common among girls and young women who are healthy and have anatomically normal urinary tracts. These infections are a main source of morbidity and health-care costs in this population. The interaction between specific infecting bacteria and urinary tract epithelium characteristics underlies the pathogenesis of this disease. Several pathogen-related factors predispose people to recurrent UTI, including periurethral bacterial colonisation and Escherichia coli virulence. Host behavioural risk factors include voiding dysfunction, high intercourse frequency, and oral contraceptive and spermicide use. The role of vesicoureteral reflux in recurrent childhood UTI is probably overestimated in the medical literature and is important only in a small group of children with high-grade reflux. Family pedigree analysis suggests a familial genetic predisposition for UTI among young females. Animal models show the multigenic nature of recurrent UTI. Putative candidate genes for the disease include ABH blood groups, interleukin-8 receptor (CXCR1), the human leucocyte antigen locus, toll-like receptors, tumour necrosis factor, and Tamm-Horsfall protein.     

Malakoplakia after kidney transplantation: Case report and literature review

Malakoplakia is a granulomatous disease associated with an infectious etiology, usually involving the urinary tract. It reveals itself as a recurrent urinary tract infection (r‐UTI), and in some cases, it is associated with impairment of renal function. Immunosuppression is one of its main associated factors, and it has been increasingly described in patients with solid organ transplantation (SOT), mainly kidney transplantation. Macroscopically, it can form masses and sometimes it may be confused with neoplasia, which is why histological findings are fundamental for the diagnosis. Here, we present a case of bladder malakoplakia, manifested by r‐UTI from Escherichia coli in a patient with renal transplantation, refractory to long‐term antibiotic treatment and reduction in immunosuppression, which resolved after surgical management. We also summarize the clinical characteristics of malakoplakia and compare them with previous reports in the literature on SOT.     

The Role of Bladder and Bowel Dysfunction (BBD) in Pediatric Urinary Tract Infections

The child with lower urinary tract symptoms, in the absence of neurological abnormalities, represents an increasingly common source of referral to the pediatric urologist. Patients with lower urinary tract dysfunction are at increased risk of urinary tract infections (UTIs), which can be a potential source of expense, inconvenience, and even morbidity and renal impairment. Many of these patients present with concomitant bowel dysfunction in the form of constipation and encopresis. As a result, the term “bladder and bowel dysfunction” (BBD) has been introduced and refers to the close relationship of the bladder and bowel and their interrelated disturbances. An in-depth understanding of BBD and its role in recurrent UTI is the key to treatment and prevention of further morbidity in these patients. We present an updated review of the literature on BBD and UTIs in children, including its pathogenesis, evaluation, and management.