What causes vesicoureteral reflux?

The causes and pathogenesis of vesicoureteral reflux have been studied for over 100 years, but to this day they have not become clearer to a significant number of clinicians and morphologists. Existing points of view on the causes and mechanism of development of vesicoureteral reflux are sometimes so contradictory that even now this issue cannot be considered fully resolved.

Vesicoureteral reflux occurs equally in boys and girls. However, before the age of one year, the disease is diagnosed predominantly in boys in a ratio of 6:1, while after 3 years, it is diagnosed most frequently in girls.

The following variants of development of vesicoureteral reflux are considered:

• the appearance of reflux against the background of congenital underdevelopment of the urinary tract without urinary tract infection;
• the appearance of reflux against the background of congenital underdevelopment of the urinary tract during the development of a urinary tract infection;
• the appearance of reflux due to genetically determined defects in the structure of the urinary system.

The development of vesicoureteral reflux is based on the disruption of the processes of connection of metanephrogenic tissue with metanephrogenic blastema and metanephrogenic diverticulum with the wall of the urinary bladder. A direct correlation was found between the degree of vesicoureteral reflux and ectopia of the ureteral orifices. There are many theories explaining the failure of the antireflux mechanism. However, the main cause of vesicoureteral reflux is currently considered to be dysplasia of the ureterovesical segment.

Congenital abnormalities of the structure of the ureteral vesicles are mainly muscle hypoplasia with their replacement by coarse collagen fibers in the wall of the distal ureter, of varying severity and prevalence. Underdevelopment of the neuromuscular apparatus and elastic framework of the ureteral wall, low contractility, and disruption of the interaction between ureteral peristalsis and bladder contractions can contribute to the occurrence and progression of vesicoureteral reflux.

The literature describes families in which reflux of varying severity occurred in several generations. There is a hypothesis about the existence of an autosomal dominant type of inheritance with incomplete penetrance of the gene or a multifactorial type of inheritance.

Vesicoureteral reflux is considered primary if it occurs due to congenital insufficiency or immaturity of the vesicoureteral segment. This is confirmed by the high frequency of vesicoureteral reflux in children compared to adult patients. The younger the child, the more often vesicoureteral reflux occurs. With age, there is a tendency for the frequency of vesicoureteral reflux to decrease. At the same time, the frequency of regression is inversely related to the degree of vesicoureteral reflux. At 1-2 degrees of vesicoureteral reflux, regression is observed in 80% of cases, and at 3-4 degrees, only in 40%.

In cases where reflux is a consequence of other diseases of the urinary bladder (neurogenic dysfunctions of the bladder, cystitis, etc.), it is considered to be toric. Until recently, many urologists considered the main cause of the development of vesicoureteral reflux to be infravesical obstruction, which is recorded in 90-92% of cases of this pathology.

In girls, one of the most common causes of secondary vesicoureteral reflux is chronic cystitis. Reversible changes in the ureterovesical segment of inflammatory origin usually cause the transient nature of reflux. However, as the duration of the disease increases, the severity of the inflammatory process increases. It spreads over a greater area and affects deeper structures of the bladder, which leads to a violation of the antireflux mechanism. Subsequent progression of the chronic inflammatory process leads to sclerotic changes in the intramural section of the ureter and atrophy of the muscular membrane, which causes rigidity, and in some cases, retraction of the obturator epithelial plate of the ureteral orifices. As a result, the orifices of the ureters begin to gape, and their edges cease to close.

Constipation contributes to compression of the lower third of the ureter and bladder, disruption of vascularization, congestion in the pelvic area, lymphogenous infection of the bladder, the development of cystitis, in addition, frequent false urges to defecate lead to an increase in abdominal pressure, inducing uninhibited fluctuations in pressure in the bladder, provoking and exacerbating pyelonephritis.

Peculiarities of the pathogenesis of vesicoureteral reflux in young children. The relevance of the problem of vesicoureteral reflux in young children is determined by its highest frequency in this group of patients due to the relative morpho-functional immaturity or malformation of the vesicoureteral segment. Having arisen at an early age, reflux contributes to the development of ureterohydronephrosis, cicatricial changes and renal growth retardation, the occurrence of reflux nephropathy, chronic pyelonephritis, chronic renal failure, which leads to disability of patients both in childhood and in more mature age.

It is often very difficult to determine the cause of vesicoureteral reflux in young children; even a pathomorphological study cannot answer the question of "congenital or acquired pathology". All this may be associated with the effect of inflammation on the relatively immature morpho-functional structures of the vesicoureteral segment of the child.

Most often, the causes leading to the development of vesicoureteral reflux are congenital. That is why reflux is more common at an early age. The most common cause of vesicoureteral reflux in young children can be morpho-functional immaturity of the upper and lower urinary tract of the vesicoureteral segment, pelvic organs, which, with the combined effect of many pathological factors, contributes to decompensation of the vesicoureteral segment, the occurrence of vesicoureteral reflux and its complications,

Age and valve function are the most important factors in the pathogenesis of reflux. This is confirmed by the existence of "reflux surprise" in newborns and infants. Currently, reflux is considered a pathology at any age. However, sometimes at an early age with vesicoureteral reflux of 1 and 2 degrees, its spontaneous disappearance may occur. Nevertheless, the data of the latest studies indicate that even with low degrees of reflux, even without its infection, nephrosclerosis may develop. Therefore, the problem of vesicoureteral reflux should be taken very seriously, and long-term follow-up observation is indicated for children.

Classification of vesicoureteral reflux

The classification of vesicoureteral reflux has been repeatedly amended and supplemented. Currently, the classification proposed by the International Committee for the Study of Vesicoureteral Reflux in Children is recommended for use.

According to this classification, primary and secondary vesicoureteral reflux are distinguished. Primary vesicoureteral reflux is understood as an isolated developmental anomaly characterized by the presence of various types of dysplasia of the vesicoureteral junction. When vesicoureteral reflux is combined with other anomalies in the development of the urinary tract, causing the development of dysfunction of the vesicoureteral junction, it is customary to speak of secondary vesicoureteral reflux.

There is also a gradation of vesicoureteral reflux depending on the degree of reflux of the radiocontrast agent and dilation of the cavity system during micturition cystography:

• 1 degree - backflow of urine from the bladder only into the distal part of the ureter without its expansion;
• 2nd degree - reflux into the ureter, pelvis and calyces, without dilation and changes in the fornix;
• Grade 3 - minor or moderate dilation of the ureter and renal pelvis in the absence of or tendency to form a right angle with fornices;
• 4th degree - pronounced dilation of the ureter, its tortuosity, dilation of the renal pelvis and calyces, roughening of the acute angle of the fornices while maintaining papillary structure in most calyces;
• Grade 5 - dilation and tortuosity of the ureter, pronounced dilation of the renal pelvis and calyces, papillary features are not visible in most calyces.

In this case, grades 4 and 5 of vesicoureteral reflux are hydronephrotic transformation.

Classification of vesicoureteral reflux

Type	Cause
Primary	Congenital insufficiency of the ureterovesical junction valve mechanism
Primary, associated with other anomalies of the ureterovesical junction	Duplication of the ureter. Ureterocele with duplication. Ectopia of the ureter Periurethral diverticula
Secondary, associated with increased pressure in the bladder	Neurogenic bladder Bladder outlet obstruction
Secondary due to inflammatory changes	Clinically expressed cystitis. Severe bacterial cystitis. Foreign bodies. Bladder stones.
Secondary due to surgical manipulations in the area of the ureterovesical junction

This classification is extremely important for determining further patient management tactics and deciding on surgical treatment.