Vesicoureteral Reflux/ Urinary reflux in infants and children

Vesicouretral Reflux or VUR refers to the abnormal flow of urine backwards from the bladder toward the kidneys. Retrograde flow of urine is a significant concern because it increases the risk of tracking bacteria up the urinary tract and developing a urinary tract infection (UTI). Urinary tract infections are the second most common type of infection in the human body, according to the NIDDK (National institute of diabetes and digestive and kidney diseases). UTI can occur in both sexes and in all ages. They are more common in females than in males. In children, UTI may be the result of an underlying anatomical glitch in the urinary tract, called Primary VUR. Studies estimate that between 25-40% of children with UTI have VUR. In order to understand the significance of retrograde flow of urine, as in VUR, we need a basic understanding of the normal functioning of the urinary system.

Urinary system

The human body derives its energy from ingested food. The waste products of this metabolic process are left in the bowels and blood. Waste in the bowels is eliminated directly. Waste products in blood are processed further and removed by the urinary system. The kidneys, ureters, bladder and urethra together compose the urinary system or urinary tract. Blood is filtered in the kidneys to remove excess water and urea, a by-product of the breakdown of protein in our diet. In addition to filtering blood, the kidneys also produce erythropoietin, a hormone that aids the formation of red blood cells. The filtrate containing the waste products emerging from the kidneys, called urine, passes through tubes called Ureters. Urine, which is sterile and hence free of bacteria and fungi, flows down the ureters to the bladder. Urine only flows towards the bladder because of valves that prevent backwards flow from the bladder to the kidney. As urine is made throughout the day, the muscles in the bladder relax, expanding the bladder like a balloon to accommodate more urine. Urine is prevented from flowing out of the bladder by sphincters that seal the bladder, like rubber bands. When the bladder is full, the brain simultaneously signals the bladder, to contract, and the sphincters, to relax, causing urine to flow out through another tube called the Urethra. Thus the flow of sterile urine is always unidirectional, from the kidneys where it is made, all the way to the urethral opening, where it leaves the body. The unidirectional flow of urine is critical for keeping infections at bay.

A urinary tract infection (UTI) occurs typically when bacteria, such as those that live in the digestive tract, start growing in the urethra. E. coli, which lives in the human gut, is the most common bacterium involved in UTI. Over time, if unresolved, the bacteria can cause a full-blown infection of the remainder of the urinary system. In children, UTI may be the result of an underlying anatomical glitch in the urinary tract, called Primary Vesicouretral Reflux (VUR). Studies estimate that VUR occurs in about 1% of children, and that between 25-40% of children with UTI have VUR. If not resolved or managed medically, VUR can lead to Pyelonephritis (infection of the kidneys), which can lead to scarring of the kidneys and hypertension.

VUR in infants/ young children

About 1/3^rd of children who develop a UTI have VUR. Any anatomical abnormalities that cause the valves to malfunction will result in the backwards flow of urine, increasing the risk of tracking bacteria up the urinary tract and developing a UTI. VUR occurs with higher likelihood in girls than in boys (twice more likely in girls) and is also more common in children younger than 2 years of age. Children whose siblings or parents have urinary reflux have a higher incidence of reflux. The severity of the reflux is assessed based on the extent of retrograde flow to the kidneys.

Diagnosis and Evaluation of VUR

The occurrence of UTI is the first and most common indicator for urinary reflux in children. Children with UTI may present with some or more symptoms such as persistent urge to urinate, burning sensation and discomfort while urinating, passing only a small amount of urine each time, bloody, cloudy or foul-smelling urine, fever and abdominal pain. In infants, UTI are harder to detect and may present as vomiting or diarrhea or high fevers (102 F in children 3 months or older and 100.4 in children younger than 3 months) with no other associated symptoms (such as runny nose etc.). In addition, there may be changes in mood, such as lethargy, persistent irritability or inconsolable crying, as well as poor appetite. Typically, a urine culture or urinalysis will be performed to detect UTI. The American academy of pediatricians (AAP) estimates that UTI are the most common serious bacterial infections that occur in infants and young children. Once a UTI has been diagnosed, further tests are performed to diagnose and grade urinary reflux, if any. The current guidelines for the care and management of UTI set by the AAP includes imaging studies that evaluate the health of the kidneys as well as the degree of retrograde flow of urine.

Renal ultrasound: Similar to the ultrasound performed to monitor the growth of fetus during pregnancy, a renal ultrasound may be performed on infants and children with UTI to detect gross abnormalities of the kidneys. High-frequency sound waves are used to image the kidneys to evaluate the size of the kidneys and detect abnormalities or obstructions, such as kidney stones, renal scarring and cysts. Although renal ultrasound, along with voiding cystourethrogram (VCUG) or radionuclide cystogram (RNC), was recommended by the AAP as part of the imaging regimen for VUR, its value in management of urinary reflux has recently been called into question. In particular, it is suggested to be superfluous for detection of congential renal defects, given the prevalence of fetal ultrasounds. Also, a renal ultrasound, by itself, is not sufficient to detect VUR.

Voiding Cystourethrogram or VCUG: VCUG uses x-rays to image the bladder after filling it with a solution containing a contrast dye via a catheter. When the bladder is full, and as it is allowed to empty by urination, images are captured in various orientations. These images, captured in real-time, indicate whether there is retrograde flow of urine, and if so, how far it reaches up the urinary tract. Depending on the extent of the retrograde flow, the reflux is graded as I through V. Grade I VUR is the mildest, with retrograde flow limited to the ureter nearest to the bladder (or distal to the kidney). Grade V VUR is the most severe, whereby the urine flows backwards into the kidney with severe dilatation, or enlargement, of the ureters and pelvis. VCUG involves irradiation of the lower abdomen, including the gonads, and is typically more important for initial diagnosis of VUR. Follow-up imaging may be performed using radionuclide cystogram (RNC) instead.

Radionuclide cystogram or RNC: In RNC a radioactive isotope-containing material, instead of a contrast dye, is injected into the bladder via a catheter. Images are then captured using a scanner that detects the radioactivity and similar data is recovered as for a VCUG. Although the discomfort from catheterization may be the same as for a VCUG, RNC uses only 1% of the ionizing radiation dose in comparison, making it the test of choice for follow-up imaging after the initial test.

Treatment of VUR

VUR is treated and managed differently, depending on the grade of reflux as well as the age of the patient. The good news is that milder grades of reflux (I, II and III) may resolve spontaneously over time, in about 80% of children with VUR. Given the reasonable chance of spontaneous resolution, a daily dose of low-dose oral antibiotics is usually prescribed to prevent kidney infections, until the reflux resolves or up to 5 years of age. Antibiotics commonly used for prohylaxis or prevention include trimethoprim-sulfamethoxazole (US brand names Bactrim, Septra), trimethoprim (Primsol) and nitrofurantoin (Furdantin, Macrodantin, Macrobid). The use of a lower dose of antibiotics, rather than the higher dose used for treating infections, helps prevent UTI that may potentially damage the kidney, while minimizing the chance of developing antibiotic-resistant bacteria in the digestive tract. More severely graded VUR (Grades IV and V) have a lower chance of spontaneous resolution. Surgical methods for correction are usually indicated for severely graded VUR, or for reflux that fails to resolve spontaneously over time, or for recurrent breakthrough UTI (UTI while on prophylactic antibiotics). Surgeries, involving general anesthesia or endoscopy, typically attempt to correct reflux either by ureteral reimplantation or use of a bulking agent (such as DefluxÒ). In traditional open surgery, ureteral reimplantation is performed by making an incision in the bladder and creating a novel, elongated tunnel for the ureter to enter the bladder. In addition, the ureter may also be narrowed. In endoscopic correction of VUR, a bulking agent is injected at the site of the ureteral opening in the bladder to prevent retrograde flow of urine. The use of endoscopic correction of VUR has increased over the last 10 years, with DefluxÒ (a bio-degradable Dextranomer/hyaluronic acid copolymer) being the bulking agent of choice, due its efficacy and safety. Following resolution of VUR, either spontaneously or by surgery, doctors may perform other tests to ensure the proper functioning of the kidneys.

“Evaluation and Treatment of Urinary Tract Infections in Children” S.M. Ahmed and S. K. Swedlund, WrightStateUniversitySchool of Medicine, Dayton, Ohio.

“Endoscopic Treatment of Vesicoureteral Reflux with Dextranomer/Hyaluronic Acid in Children”, W. H. Cerwinka, H. C. Scherz, and A. J. Kirsch, Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA.Advances in Urology, 2008; 2008, 513854.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2441859/pdf/AU2008-513854.pdf 

“Vesicoureteral Reflux: The Role of Antibiotic Prophylaxis”, E. R. Wald, Children’s hospital of Pittsburg, Pittsburg, PA.Pediatrics, 2006; 117 (3), 919. http://pediatrics.aappublications.org/cgi/reprint/117/3/919

 “Vesicoureteral Reflux and Urinary Tract Infection: Evolving Practices and Current Controversies in pediatric Imaging”, R. Lim, Division of Pediatric Radiology and Division of Nuclear Medicine Molecular Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA. American Journal or Roentgenology, 2009; 192, 1197. http://www.ajronline.org/cgi/reprint/192/5/1197

“Practice Parameter: The Diagnosis, Treatment, and Evaluation of the Initial Urinary Tract Infection in Febrile Infants and Young Children”, AmericanAcademy of Pediatrics, Committee on Quality Improvement, Subcommittee on Urinary Tract Infection.Pediatrics, 1999; 103(4), 843. http://aappolicy.aappublications.org/cgi/reprint/pediatrics;103/4/843.pdf

 Mayo Clinic http://www.mayoclinic.com/health/vesicoureteral-reflux/DS00999