Vesicoureteral Reflux Research

Normally, urine that is produced in our kidneys travels down the two ureters (i.e. muscular transport tubes) to the bladder and then from there out of the body via the urethra. The abnormal and reversed flow of urine from the bladder to the upper parts of the urinary system is referred to as vesicoureteral reflux (VUR).  It is most often seen in very young children and infants.

VUR may be primary or secondary. Primary VUR is congenital and occurs when the ureter is shorter than it should be and/or if the ureteric valve in the bladder fails to close properly. With the growth of the child, the ureters lengthen and valvular function may improve. Secondary VUR, on the other hand, is due to blockage within the urinary system that forces urine to travel in a retrograde fashion.

Diagnosis is made on the basis of findings with either a voiding cystourethrogram (i.e. an X-ray of the urethra and bladder during urination), radionuclide cystogram (i.e. a scan with radioactive agents) and/ or an abdominal ultrasound. The latter does not use ionizing radiation in contrast to the former two. Treatment depends on etiology, but may include antibiotics, intermittent catheterization and surgery.

Antibiotic prophylaxis may not be always necessary

It was common practice in the past to prescribe antibiotics prophylactically to all affected children, regardless of the severity of their VUR. This trend is being abandoned by many, because the latest research into VUR management suggests that the risks involved in using global antibiotic prophylaxis may actually outweigh the benefits. These risks include complications, such as renal scarring and antimicrobial resistance. Some researchers have observed that prophylaxis may be useful in only half of the cases in reducing the recurrence of urinary tract infections (UTIs) and fails to significantly decrease the chances of renal scarring.

The findings of these investigators are interesting. This is because antibiotic prophylaxis aims to prevent UTIs in the first instance and eliminate the possibility of UTIs developing into pyelonephritis, which is severe and may lead to scarring of the kidneys.  Even more interesting, is that this research contradicts findings by other groups of investigators. Thus, it is not fully established if antibiotic prophylaxis should or should not be given to all children with VUR. Some suggest using antibiotic prophylaxis only with higher grades of VUR but other preventative means in those with lower-grade VUR and no recurrent UTIs.

Link between Pax2 and VUR

Some researchers have discovered a potential correlation between the transcription factors Pax2 and VUR.  Pax2 plays a crucial role in the development of the urinary system as a nuclear transcription factor. In a small group of VUR patients, the ureteral expression of Pax2 was measured and found to be significantly increased with an accompanying decrease in Dnmt3a. The latter is a vital enzyme for the process of DNA methylation. Thus, it is speculated that the decrease in Dnmt3a is directly proportional to the hypo-methylation of Pax2 and resultant upregulation in the expression of the Pax2 protein found in the test group of VUR patients, leading to a possible relation between functional ureteral lesions and cellular apoptosis.

Reviewed by Liji Thomas, MD.

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Last Updated: Aug 24, 2017

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