Vesicoureteric reflux and reflux nephropathy as seen at a tertiary care adult nephrology service in India--an analysis of 86 patients

Clinical features and risk factors for renal failure in patients with reflux nephropathy (RN) as seen in an adult nephrology service are likely to be different than those seen in a pediatric service. There are only a few studies on adults with vesicoureteric reflux (VUR) and RN and data on RN as seen in developing countries is still evolving. Retrospective analysis of records of patients diagnosed to have VUR by conventional micturating cystourethrogram over a 13 year period, as seen in the adult nephrology services of this tertiary care hospital in north India was carried out. Results are presented as mean +/- 2 SD. Unpaired t-test was used to compare means, chi-square test to define associations, and logistic regression analysis was done to define risk factors. Out of 86 patients diagnosed to have VUR, 69 (80.2%) were males and 22 (25.6%) were children. The mean age at presentation was 24.3 +/- 14.5 years and at onset of symptoms was 19.64 +/- 14.8 years. Sixty-nine (80.2%) patients had chronic renal failure (CRF) at presentation, including 33 (38.4%) patients who already had end stage renal failure (ESRF) at presentation in whom reflux was diagnosed during routine pretransplant evaluation and these constituted 5.5% of all ESRF patients. The clinical features at presentation were hypertension in 51 (59.3%), recurrent urinary tract infection (UTI) in 31 (36.1%), history of stones in 7 (8.1%), and gross hematuria in 4 (4.7%). Patients with history of recurrent UTI were more likely to be females (p < 0.01) and to present without renal failure (p < 0.05). Proteinuria > 1 g/day was significantly associated (p < 0.02) with hypertension at presentation. Patients who presented with renal failure were more likely to be males (p < 0.05), not to have history of recurrent UTI (p < 0.05), have proteinuria > 1 g/day (p < 0.02) and higher grades (grades IV and V) of reflux (p < 0.05). On logistic regression analysis, higher age of onset (odds ratio 4.6, p < 0.03), proteinuria > 1 g/day (odds ratio 3.8, p < 0.05), and male gender (odds ratio 3.5, p < 0.05) were significant risk factors for presentation for the first time with renal failure. The clinical features and course of VUR and RN as seen in India are different from those reported from elsewhere. The vast majority of patients in India are males and almost two thirds do not have a past history of UTI. Renal failure is present in more than three fourths of patients when a diagnosis of reflux is made and one third of all patients present with ESRD. Patients with a prior history of UTI are more commonly females and are less likely to have renal failure at presentation. Higher age of onset of symptoms, proteinuria > 1 g/day and male gender were risk factors for the development of renal failure. It is likely that these asymptomatic patients remain undetected during childhood, presenting late only after having incurred severe renal damage.     

Surgical management of vesicoureteral reflux in children

Vesicoureteral reflux (VUR) is the most common uropathy affecting children. Compared to children without VUR, those with VUR have a higher rate of pyelonephritis and renal scarring following urinary tract infection (UTI). Options for treatment include observation with or without antibiotic prophylaxis and surgical repair. Surgical intervention may be necessary in patients with persistent reflux, renal scarring, and recurrent or breakthrough febrile UTI. Both open and endoscopic approaches to reflux correction are successful and reduce the occurrence of febrile UTI. Estimated success rates of open and endoscopic reflux correction are 98.1% (95% CI 95.1, 99.1) and 83.0% (95% CI 69.1, 91.4), respectively. Factors that affect the success of endoscopic injection include pre-operative reflux grade and presence of functional or anatomic bladder abnormalities including voiding dysfunction and duplicated collecting systems. Few studies have evaluated the long-term outcomes of endoscopic injection, and with variable results. In patients treated endoscopically, recurrent febrile UTI occurred in 0–21%, new renal damage in 9–12%, and recurrent reflux in 17–47.6% of treated ureters with at least 1 year follow-up. These studies highlight the need for standardized outcome reporting and longer follow-up after endoscopic treatment.     

Vesicoureteric reflux and renal injury

Renal injury associated with the intrarenal reflux (IRR) of urine that is either infected, under high pressure, or both, is a major cause of severe hypertension during childhood and adolescence and of chronic renal insufficiency in patients less than 30 years of age. Many, but not all, adolescent and adult patients with reflux nephropathy (RN) give a history of urinary tract infection (UTI) or unexplained fevers in infancy or early childhood, when the kidney is thought to be at greatest risk of injury. Although vesicoureteric reflux (VUR) is observed more commonly in infants than children with UTI, it is rare in uninfected patients at any age and should never be considered a normal finding during human development. Renal scarring may not be obvious in radiographic or radionuclear studies to medical management alone, no definite benefit of one over the other was observed, regardless of the grade of VUR. Moreover, progressive renal injury in scarred kidneys has been noted even after VUR had been corrected, when infection had been prevented, and while hypertension had been controlled satisfactorily. Focal glomerular sclerosis, a lesion found in patients with proteinuria and RN, has been identified not only in scarred kidneys, but also may be seen in contralateral, unscarred kidneys without VUR, which might suggest a humoral factor or, perhaps, a hyperfiltration phenomenon. RN is one of the most frequent causes of end-stage renal disease (ESRD) in children, adolescents, and young adults, which is potentially preventable. However, prevention will depend on early identification of patients at risk--infants and young children after the first UTI and siblings of patients with VUR--aggressive and effective treatment of UTI, minimizing intravesical pressure, and education of patients, parents, and physicians.     

Vesicoureteral reflux, a benign condition

The combination of urinary tract infection (UTI) and vesicoureteral reflux (VUR) is commonly thought to predispose the child to pyelonephritis, renal scarring and, later in life, to hypertension or end-stage renal disease (ESRD). This paradigm has led to the active search, follow-up and treatment of VUR, and also prevention of recurrent UTI in children. The causality of VUR and ESRD is controversial, however. According to recent meta-analyses it is uncertain whether we can prevent renal scarring or ESRD by treating VUR. Studies on VUR are abundant, but the findings and conclusions are confounding. Because of the lack of evidence of the role of VUR, reasonable doubt has recently been presented on the rationale of imaging all children with UTI and treating the children with VUR. The overall importance of VUR is confounded because of the natural tendency of VUR to resolve spontaneously, its dynamic nature, and its different grades in children. The historical studies showing that VUR is much more common, even among healthy children, than usually claimed, have been forgotten. Since it seems that we are referring too many healthy children to unpleasant and possibly unnecessary imaging tests for VUR, we are uncertain when and what kind of VUR—if any—we should treat, and whether our present rationale of addressing VUR truly makes any difference to renal scarring or ESRD in children, we should critically revisit the subject of VUR.     

Medical management of vesicoureteral reflux

Vesicoureteral reflux (VUR) in children is associated with increased risk of urinary tract infection (UTI). Recurrent UTI in the presence of the VUR is believed to cause renal scarring, which carries a risk of subsequent hypertension, toxemia of pregnancy, and significant renal damage, including end-stage renal disease. The natural history of VUR is to improve or resolve completely with time in most of the patients. The traditional management consists of prompt treatment of UTI, long-term anti-microbial prophylaxis until the VUR resolves, or surgical intervention in those with persistent high grade VUR, recurrent UTI in spite of prophylaxis with anti-microbial agent, allergy to anti-microbial agents, and patient/parent non-compliance with the medical management. Voiding dysfunction and constipation play an important role, and their diagnosis and appropriate management helps reduce the frequency of UTI and promote the resolution of the VUR. Patients with renal scarring need to be monitored for potential complications such as hypertension, proteinuria, and progression of the renal damage. In patients with hypertension and/or proteinuria, angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) are the drugs of choice, because of their reno-protective properties. Recent studies have revealed that there is no convincing evidence that UTI in the presence of VUR predicts renal injury or that the use of long-term anti-microbial prophylaxis or surgical intervention prevents renal scarring or its progression. However, until proven otherwise by a prospective, placebo-controlled, randomized study, it is advisable to err on the side of caution and consider VUR and UTI risk factors for renal scarring and treat each patient on individual basis.     

Vesicoureteric Reflux and Reflux Nephropathy as Seen at a Tertiary Care Adult Nephrology Service in India—An Analysis of 86 Patients

Clinical features and risk factors for renal failure in patients with reflux nephropathy (RN) as seen in an adult nephrology service are likely to be different than those seen in a pediatric service. There are only a few studies on adults with vesicoureteric reflux (VUR) and RN and data on RN as seen in developing countries is still evolving. Retrospective analysis of records of patients diagnosed to have VUR by conventional micturating cystourethrogram over a 13 year period, as seen in the adult nephrology services of this tertiary care hospital in north India was carried out. Results are presented as mean ± 2 SD. Unpaired t-test was used to compare means, chi-square test to define associations, and logistic regression analysis was done to define risk factors. Out of 86 patients diagnosed to have VUR, 69 (80.2%) were males and 22 (25.6%) were children. The mean age at presentation was 24.3 ± 14.5 years and at onset of symptoms was 19.6 ± 14.8 years. Sixty-nine (80.2%) patients had chronic renal failure (CRF) at presentation, including 33 (38.4%) patients who already had end stage renal failure (ESRF) at presentation in whom reflux was diagnosed during routine pretransplant evaluation and these constituted 5.5% of all ESRF patients. The clinical features at presentation were hypertension in 51 (59.3%), recurrent urinary tract infection (UTI) in 31 (36.1%), history of stones in 7 (8.1%), and gross hematuria in 4 (4.7%). Patients with history of recurrent UTI were more likely to be females (p<0.01) and to present without renal failure (p<0.05). Proteinuria >1 g/day was significantly associated (p<0.02) with hypertension at presentation. Patients who presented with renal failure were more likely to be males (p<0.05), not to have history of recurrent UTI (p<0.05), have proteinuria >1 g/day (p < 0.02) and higher grades (grades IV and V) of reflux (p<0.05). On logistic regression analysis, higher age of onset (odds ratio 4.6, p<0.03), proteinuria >1 g/day (odds ratio 3.8, p<0.05), and male gender (odds ratio 3.5, p<0.05) were significant risk factors for presentation for the first time with renal failure. The clinical features and course of VUR and RN as seen in India are different from those reported from elsewhere. The vast majority of patients in India are males and almost two thirds do not have a past history of UTI. Renal failure is present in more than three fourths of patients when a diagnosis of reflux is made and one third of all patients present with ESRD. Patients with a prior history of UTI are more commonly females and are less likely to have renal failure at presentation. Higher age of onset of symptoms, proteinuria >1 g/day and male gender were risk factors for the development of renal failure. It is likely that these asymptomatic patients remain undetected during childhood, presenting late only after having incurred severe renal damage.     

Summary of recent AUA guidelines for the management of vesicoureteral reflux in children

VUR is a common condition and it is a predisposing factor for pyelonephritis, and reflux nephropathy, which can cause end stage renal disease in children. Given the consequences and sequelae of UTI and VUR, and due to lack of consensus regarding management of this common condition, the American Urological Association (AUA) developed treatment guidelines for children with VUR in 1997 and 2012 to help physicians better manage children with VUR. In this review, the summary of the 1997 and 2012 AUA guidelines are discussed with a focus on the 2012 report. Recommendations about evaluation and management of children under and above one year with VUR, with and without bladder/bowel dysfunction, screening of siblings of patients with VUR, screening of the neonate/infant with prenatal hydronephrosis, and follow up of the children with VUR are discussed in this review. The identification and management of VUR in these groups, provide the potential opportunity to prevent renal damage and decrease the risk of UTI and pyelonephritis. According to these guidelines, risk assessment of renal injury/scarring in the individual patient based upon clinical factors is critical, and interventions should be appropriate to the risk profile. Informing families and healthcare providers of the potential risk of pyelonephritis and renal scarring and allowing them to participate in decision making is considered important.     

Primärer vesikoureteraler Reflux

The never ending discussion about the diagnostics and treatment of vesicoureteral reflux (VUR) now includes arguments for diagnostic nihilism as well as invasive diagnostics and therapy, which is reminiscent of the debate on prostate cancer in adulthood. The common goal of all currently competing diagnostic strategies and approaches is the prevention of renal scars by the most effective and least burdensome approach. There is a difference between acquired pyelonephritic scars with VUR (acquired reflux nephropathy) and congenital reflux nephropathy (primary dysplasia) which cannot be influenced by any therapy. The VUR can be verified by conventional radiological voiding cystourethrography (VCUG), by urosonography, radionuclide cystography or even by magnetic resonance imaging (MRI). The guidelines of the European Association of Urology/European Society for Paediatric Urology (EAU/ESPU) recommend radiological screening for VUR after the first febrile urinary tract infection. Significant risk factors in patients with VUR are recurrent urinary tract infections (UTI) and parenchymal scarring and the patients should undergo patient and risk-adapted therapy. Infants with dilating reflux have a higher risk of renal scarring than those without dilatation of the renal pelvis. Bladder dysfunction or dysfunctional elimination syndrome represents a well-known but previously neglected risk factor in combination with VUR and should be treated prior to any surgical intervention as far as is possible. Certainly not every patient with VUR needs therapy. The current treatment strategies take into account age and gender, the presence of dysplastic or pyelonephritic renal scars, the clinical symptoms, bladder dysfunction and frequency and severity of recurrent UTI as criteria for the therapy decision. The use of an antibacterial prophylaxis as well as the duration is controversially discussed. Endoscopic therapy can be a good alternative to antibacterial prophylaxis or a surveillance strategy in patients with low grade VUR. In patients with dilating VUR and given indications for surgery, endoscopic treatment can be offered. However, parents should be completely informed about the significantly lower success rate of endoscopic therapy compared to open surgical procedures. The open surgical techniques guarantee the highest success rates and should be used in patients with a dilating VUR and high risk of renal damage.     

Vesicoureteric reflux and reflux nephropathy: from mouse models to childhood disease

Vesicoureteric reflux (VUR) is a common congenital urinary tract defect that predisposes children to recurrent kidney infections. Kidney infections can result in renal scarring or reflux nephropathy defined by the presence of chronic tubulo-interstitial inflammation and fibrosis that is a frequent cause of end-stage renal failure. The discovery of mouse models with VUR and with reflux nephropathy has provided new opportunities to understand the pathogenesis of these conditions and may provide insight on the genes and the associated phenotypes that need to be examined in human studies.     

Prevalence of hydronephrosis and vesicoureteral reflux in pediatric urinary tract infection

We studied 108 children diagnosed with urinary tract infection (UTI) to determine the frequency of hydronephrosis and vesicoureteral reflux (VUR). Fifty-two children (48.1%) had hydronephrosis (pyeloureteral junction obstruction: 27.8%) and 43 children (39.8%) had VUR (primary VUR: 36.1%). A renal scar was seen in 25.8% of the VUR cases. We recognized again that children with a history of UTI need to be examined promptly and thoroughly.     

Recurrence and follow-up after urinary tract infection under the age of 1 year

In order to analyze the risk factors for recurrence and the value of routine follow-up by monthly urine cultures in a group of children who had their first episode of urinary tract infection (UTI) under 1 year of age, we performed a retrospective survey of 262 children (134 girls, 128 boys) who were treated for their first UTI while aged under 1 year in the Department of Pediatrics, University of Oulu, during the years 1978–1984. Detailed data on these children concerning their first and recurrent UTIs were collected from hospital records using a formulated data sheet. Causative bacteria and vesicoureteral reflux (VUR) were analyzed as possible risk factors for recurrent UTI. The time of recurrence and the possible symptoms during the recurrent UTI were also investigated. The follow-up period after the first UTI was 3 years; 35% of the boys and 32% of the girls contracted a recurrent UTI during the 3-year follow-up. In 86% of cases, the first UTI recurrence occurred within 6 months of the primary UTI. Recurrent UTIs were detected significantly earlier with routine monthly follow-up compared with those seeking treatment because of symptoms (log rank test P<0.01). There was a significant difference in the number of recurrences of UTI according to the grade of VUR (P=0.006). Recurrence-free survival was shorter and recurrent UTIs occurred more often in the children with grade 3–5 VUR than in those with grade 0–2 VUR (log rank test P=0.0005). Children without VUR and children with grade 1–2 VUR did not differ in the recurrence rate, and thus grade 1–2 VUR did not increase the risk for recurrent UTI. Monthly routine urine cultures are efficient in detecting recurrent UTI infections in children. Since grade 3–5 VUR is a risk factor both for increased recurrence rate of UTI and for possible subsequent renal damage, these children should be followed with monthly urine cultures for UTI recurrences if not on preventive medication. Since the vast majority of UTI recurrences occur within 6 months of the first UTI, routine follow-up for 6 months seems to be sufficient after symptomatic UTI in children with grade 3–5 VUR. Received: 10 January 2000 / Revised: 21 August 2000 / Accepted: 21 August 2000     

Evidence for and against urinary prophylaxis in vesicoureteral reflux

The role of antimicrobial prophylaxis in vesicoureteral reflux (VUR) has come under increasing scrutiny because of better analytical methods in the published literature, knowledge gained from VUR and renal scars diagnosed without preceding urinary tract infection (UTI), and better renal imaging modalities for diagnosing renal scars. A meta-analysis of the five recent randomized studies with a total of 809 patients with VUR diagnosed after UTI reveals a relative risk of UTI recurrence of 0.82 [95% confidence interval (CI) 0.62–1.08; p?=?0.16) with prophylaxis. A meta-analysis of the four studies with a total of 662 patients with UTI with and without VUR evaluated for renal scarring reveals a relative risk of 1.04 (95% CI: 0.84–1.30; p?=?0.69), according to Springer style?> with prophylaxis. However, these observations need to be interpreted with caution because of the limitations with these studies and their heterogeneity for meta-analysis, particularly for renal scarring. More research is needed to validate the role of prophylaxis in VUR diagnosed after UTI, and even more research is warranted to answer the questions regarding antimicrobial prophylaxis across the spectrum of VUR in different clinical settings.     

Primary vesicoureteric reflux and renal damage in the first year of life

We retrospectively examined 93 children (47M/46F) with primary vesicoureteric reflux (VUR) followed for a mean period of 3.5 years. They were divided into two groups. Group A included 34 babies (25M/9F) with a prenatal diagnosis of pelvic dilatation. Mean age at presentation was 12 days and no urinary tract infection (UTI) occurred before our first examination. VUR was unilateral in 21 (62%) patients and bilateral in 13 (38%). It was mild (grades I–III) in 12 (25%) refluxing renal units (RRU) and severe (grades IV–V) in 35 (75%). Renal damage (RD) was present, at diagnosis, in 40 (85%) RRU. There was a greater prevalence of abnormal kidneys in male units (88%) than in female units (75%). Group B included 59 infants (22M/37F) less than 1 year old with UTI. The mean age at first examination was 7.6 months. VUR was unilateral in 32 (54%) infants and bilateral in 27 (46%), mild in 60 (70%) RRU and severe in 26 (30%). At diagnosis, 54 (63%) RRU presented RD, which was more common in females (66%) than in males (44%). Our study confirms that primary VUR associated with prenatal hydronephrosis usually affects males and is severe. VUR diagnosed after UTI, instead, is more common in females and is frequently mild. Although in the first type of reflux RD is often present at diagnosis, then probably congenital, it may always progress after UTI; hence the importance of early diagnosis and careful follow-up in each infant with primary VUR. Received: 9 August 1999 / Revised: 3 April 2000 / Accepted: 7 July 2000     

Relationship between acute pyelonephritis, renal scarring, and vesicoureteral reflux

Acute pyelonephritis (APN) may produce permanent renal damage (PRD), which can subsequently lead to diverse complications. We prospectively evaluated 147 females and 122 males (mean age 3.5 years) with APN in order to analyze the relationship between the presence of PRD, at the time of cortical renal scintigraphy, and age, gender, episodes of urinary tract infection (UTI), and presence of vesicoureteral reflux (VUR). There were 152 children studied after the first proven UTI. VUR was present in 150 children. PRD was observed in 170 children. There were no significant differences between boys and girls. PRD was found in 36.4% of children younger than 1 year and in 70.1% of those older than 1 year (P<0.0001). Of children with VUR, 72% had PRD compared with 52% of children without VUR (P<0.0001). Of children with a first episode of UTI, 55.9% developed PRD as did 72.6% of those with recurrent UTI (P=0.004). Our results showed that PRD in children with APN is important, especially in the presence of VUR, recurrent UTI, and older age.     

Vesicoureteral reflux and reflux nephropathy

Vesicoureteral reflux is an anatomic abnormality, mostly affecting a pediatric population, which may be the second leading cause of end-stage renal failure. Most cases of reflux are due to abnormalities in the insertion of the ureters into the bladder, either congenital or acquired. Most commonly, VUR is discovered during routine evaluation of urinary tract infections, but may also be present in patients with severe hypertension or chronic renal failure. The diagnosis is confirmed radiologically, utilizing either voiding cinecystography or radioisotopic methods. VUR can result in renal failure through scarring secondary to 'chronic pyelonephritis' or through a glomerulopathy, possibly immune in origin. In most series, the glomerulopathy is felt to be the cause of the end-stage renal failure. Treatment of VUR includes conservative (medical) management with the hope that maturation of the ureterovesical junction will cure reflux. Surgical therapy is reserved for those patients in whom this maturation is not expected to occur or in those whose urinary infections cannot be controlled. In those patients who have developed the glomerulopathy secondary to VUR, surgery may not halt the progression of the renal disease. VUR in a transplanted kidney may result in a higher risk of loss of the graft due to glomerulopathy or chronic rejection.     

Severe bilateral vesicoureteral reflux and nephropathy in male newborns: valve-like syndrome or uncoordinated voiding in the male fetus

OBJECTIVES: Various papers differentiating neonatal vesicoureteral reflux (VUR) with severe renal damage from other predominant group of newborns with neonatal VUR without renal lesions and those diagnosed in older ages, generally in relation with urinary tract infection (UTI), have been published over the last decade. From the standpoint that VUR is part of a broad spectrum both in clinical expression as in pathogenesis, with different theories described to explain the existence of this type of congenital VUR in males. The existence of a fetal vesicourethral dysfunction, presenting after birth as a high risk bladder, which is defined by urodynamic tests in the first trimester, explains the appearance of severe fetal VUR with functional deterioration of one or both renal units at the time of birth; this entity must be diagnosed to establish the adequate therapeutic management. This clinical picture is named Valve like syndrome or male uncoordinated fetal voiding.     

Routine evaluation of vesico-ureteric reflux in children with anorectal malformation does not reduce the rate of urinary tract infection

ObjectiveChildren with anorectal malformations (ARM) have a high rate of renal anomalies and increased risk of urinary tract infection (UTI). We aimed to determine whether using routine Micturating Cystourethrogram (MCUG) to detect VUR is effective in reducing the incidence of UTI or renal scarring in children with ARM.MethodsA retrospective study of consecutive children diagnosed with ARM in two centres with a minimum of 3 years follow-up was performed, excluding those with cloaca or an MCUG prior to ARM repair. Univariate and multivariate logistic regression analysis was used to determine variables which were associated with VUR, UTI and renal scarring. Associations are described as Odd's Ratio (OR), 95% Confidence Interval. Significance was taken as p<0.05.Results344 children were included with a median age of 8 years (IQR 5–11 years). 150 (44%) were female. 89 (26%) had renal anomalies and 101 (29%) had spine anomalies. 148 patients had routine MCUG and VUR was found in 62 (42%) of these children. Univariate analysis did not correlate any of the assessed variables with VUR or renal scarring. However, abnormal renal ultrasound - OR 6.18 (95% CI 2.99–13.07, p 0.0001) was associated with UTI whilst abnormal spine - OR 0.27 (95% CI 0.10–0.62, p 0.009), low ARM - OR 0.30 (CI 0.14–0.63, p 0.006) and intermediate ARM - OR 0.35 (CI 0.17–0.70, p 0.01) were associated with a reduced risk of UTI. On multivariate analysis, only abnormal renal USS retained a significant association with UTI (p<0.0001).ConclusionsVUR is common in patients with ARM. Children with an abnormal R-USS are at increased risk of UTI. Performing routine MCUG does not reduce the risk of UTI in children with ARM.     

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.     

Vesicoureteral reflux

Vesicoureteral reflux (VUR), the retrograde flow of urine from the bladder toward the kidney, is common in young children. About 30% of children with urinary tract infections will be diagnosed with VUR after a voiding cystourethrogram. For most, VUR will resolve spontaneously; 20% to 30% will have further infections, but few will experience long-term renal sequelae. Developmentally, VUR arises from disruption of complex signaling pathways and cellular differentiation. These mechanisms are probably genetically programmed but may be influenced by environmental exposures. Phenotypic expression of VUR is variable, ranging from asymptomatic forms to severe renal parenchymal disease and end-stage disease. VUR is often familial but is genetically heterogeneous with variability in mode of inheritance and in which gene, or the number of genes, that are involved. Numerous genetic studies that explore associations with VUR are available. The relative utility of these for understanding the genetics of VUR is often limited because of small sample size, poor methodology, and a diverse spectrum of patients. Much, if not all, of the renal parenchymal damage associated with end-stage disease is likely to be congenital, which limits the opportunity for intervention to familial cases where risk prediction may be available. Management of children with VUR remains controversial because there is no strong supportive evidence that prophylactic antibiotics or surgical intervention improve outcomes. Furthermore, well-designed genetic epidemiological studies focusing on the severe end of the VUR phenotype may help define the causal pathway and identify modifiable or disease predictive factors.     

Urinary tract infection: one lingering effect of childhood kidney diseases--review of the literature

Urinary tract infection (UTI) is a possible warning sign of the presence of anomalies of the urinary tract. Following a UTI there is concern with recurrences which can contribute to scarring which may lead to hypertension, pregnancy-induced hypertension and even renal failure in later years. Prospective studies using 99mTc-labeled dimercaptosuccinic acid (DMSA) have shown that 30%-40% of children will have renal scarring after febrile UTI, regardless of the presence or absence of vesicoureteral reflux (VUR). Many studies have demonstrated that VUR is an important risk factor for renal scarring after UTI. Hypertension affects at least 10% of children with renal scarring, and in adults with reflux nephropathy (RN), the prevalence of hypertension is also much higher (38%-50%). UTI, pregnancy-induced hypertension (PIH) or renal function deterioration alone or in some combination has been reported to be as high as 39% in women with renal scarring. RN is one of the important causes of end-stage renal disease (ESRD) worldwide. Prevention of renal scar development should reduce the incidence of hypertension in patients as they age. The appropriate management of childhood UTI includes education of parents, patients and general physicians to be sure that everyone is aware of not only the current condition, but also the possibility of future UTI-related situations. In conclusion: UTI itself is a warning sign of possible anomalies of the urinary tract, renal problems and/or chronic renal complications. Although VUR is primarily a disease of childhood, scarring from the disease can cause problems in later years, with the complicating factor that because only the renal scar remains, the VUR may be forgotten and not considered when diagnosing the current problem.