Primary vesicoureteral reflux in children

　　The etiology of primary vesicoureteral reflux in children mainly includes anatomical and physiological characteristics, congenital developmental abnormalities, and urinary tract infections, etc., as follows:

　　1. Anatomical and physiological characteristics

　　The anatomical and physiological characteristics of the ureterovesical junction are closely related to the formation of reflux. The normal ureteral muscle layer is mainly composed of loose irregular spiral muscle fibers, which become longitudinal fibers only when entering the bladder wall segment, and are wrapped by a fibrous membrane called the Waldeyer sheath, which descends and attaches to the deep trigone area of the bladder. This sheath acts as a valve function for the ureterovesical junction. When the bladder voids, the sheath contracts to close the ureteral orifice, preventing urine from refluxing into the ureter.

　　2. Congenital maldevelopment

　　The cause of reflux is congenital maldevelopment of the ureterovesical junction, mainly due to the maldevelopment of the longitudinal muscle in the ureteral segment within the bladder wall, causing the ureteral orifice to be laterally displaced, the submucosal segment of the ureter to be shortened, and thus losing the ability to prevent reflux. Another reason is that the length of the submucosal segment of the ureter is not proportionate to its caliber. Normally, without reflux, the length of the submucosal segment of the ureter is in a ratio of 5:1 to its diameter, while in those with reflux, it is only 1.4:1. In addition, paraureteral diverticula, ureteral orifice opening into a bladder diverticulum, ectopic ureteral orifice, and bladder dysfunction can also cause vesicoureteral reflux.

　　The valve function of the ureterovesical junction depends on the length of the submucosal segment of the ureter in the bladder and the ability of the trigone muscle layer to maintain this length, as well as the sufficient support of the detrusor muscle for this segment of the ureter. In infancy, due to the congenital maldevelopment of the ureteral segment in the bladder wall, it is too short (less than 6mm) or horizontal, the trigone area is not mature, and the valve mechanism loses its normal function; the ureteral orifice opening is ectopic and morphologically abnormal, which can affect the tension of the trigone area and is prone to reflux, as shown in Figure 1.

　　Dysfunction of the detrusor muscle causes reflux urine to reflux from the bladder into the ureter or renal pelvis. When the bladder expands, urine returns to the bladder, causing incomplete bladder emptying and increased residual urine. When the intravesical pressure rises, the submucosal segment of the ureter is compressed without producing reflux, and this valve mechanism is passive. However, the peristaltic ability of the ureter and the closing ability of the ureteral orifice also play a part in preventing reflux. With age, the development of the ureterovesical junction and the trigone area gradually becomes perfect, the valve function is restored, and reflux can gradually disappear. Due to the continuous increase in intravesical pressure, the ureterovesical junction is deformed, and the anti-reflux mechanism is destroyed.

　　3. Urinary tract infection

　　Inflammatory changes in urinary tract infections often cause the ureterovesical junction to lose its valve function, leading to reflux. In recent years, it is believed that reflux is related to genetic factors. In families with reflux nephropathy, patients with the same reflux are often due to dominant gene inheritance or sex-linked inheritance, related to tissue compatibility antigens HLA-A3, B12. In patients with reflux, familial cases account for 27% to 33%.

　　Primary cases are often congenital, without associated urinary system neuromuscular abnormalities or obstructive factors. The main cause is congenital maldevelopment of the ureterovesical junction, leading to incomplete valve function or congenital weakness of the trigone muscle of the bladder. Commonly, the ureteral channel in the bladder wall segment is shortened, the ureteral orifice is laterally displaced or opens like a golf ball hole. In cases of supernumerary kidneys with two ureters, there is often congenital maldevelopment of the ureteral orifice opening. When the bladder contracts, urine refluxes into the ureter.

　　The main complications of primary vesicoureteral reflux in children are urinary tract infection, renal积水, and severe kidney damage can lead to hypertension and renal failure. The occurrence of hypertension is related to renal scars, and the more renal scars, the higher the risk of hypertension. Children with bilateral severe scars have a 20% incidence of hypertension after 20 years of follow-up, and 8% for unilateral lesions. If the reflux is not effectively controlled and renal scars continue to develop, renal failure may occur.

　　The symptoms of primary vesicoureteral reflux are mainly manifested from two aspects: renal积水 and urinary tract infection. Reflux leads to the inability to empty urine in the upper urinary tract, which will produce dilatation of the renal pelvis and ureters to a certain extent, reflected by ultrasound. Therefore, all renal积水 detected by ultrasound should undergo VCUG to exclude reflux. Due to the fact that a considerable number of children have asymptomatic reflux, ultrasound screening for reflux in high-risk populations has practical significance. Urinary tract infection in children is more often manifested as non-specific symptoms, including fever, drowsiness, weakness, anorexia, nausea, vomiting, and growth disorders. In infants, asymptomatic reflux can manifest as renal colic, but the symptoms are atypical. Older children can point out rib pain during bladder filling or micturition. In older children with concurrent acute pyelonephritis, there may also be lumbar and abdominal pain and tenderness.

　　The prevention and treatment of primary vesicoureteral reflux in children mainly aim to prevent and control the occurrence and progression of renal damage. The most important is to stop urine reflux and control infection. Due to the lack of effective treatment, it is important to seek early diagnosis and treatment at a good hospital with modern equipment as soon as the disease is suspected. Early treatment, control of infection, hypertension, and proteinuria should be done. When renal insufficiency occurs, a high-quality low-protein diet should be adopted to delay the onset of end-stage renal failure.

　　The main examinations for primary vesicoureteral reflux in children include laboratory tests and other auxiliary examinations, as follows:

　　1. Laboratory examination

　　Routine microscopic or electron microscopic scanning examination of urine should consider the presence of reflux nephropathy if there is an increase in tubular epithelial cells and atypical red blood cells. Proteinuria can be the initial symptom of reflux nephropathy. Increased excretion of urinary microalbumin (including urinary β2-microglobulin, α1-microglobulin, retinol-binding protein, urinary albumin) and urinary N-acetyl-β-glucosaminidase (NAG) can greatly help in the diagnosis of early reflux nephropathy and renal scar formation. Decreased urinary Tamm-Horsfall protein reflects tubular dysfunction, and significant reduction is seen in chronic pyelonephritis and chronic renal parenchymal lesions.

　　II. Other auxiliary examinations

　　1. Ultrasound examination: Real-time B-ultrasound examination is suitable for the screening examination of diagnosing reflux, if there is dilatation of the ureter and renal pelvis, it should be considered that there is reflux. Now, color Doppler ultrasound examination is used to observe the reflux condition during micturition after bladder filling, and can also observe the position of the ureteral orifice, which is conducive to early diagnosis, the method is safe, and there is no pain or injury.

　　2. Radionuclide cystography: Can accurately determine whether there is reflux, but is not precise enough to determine the grade of reflux and can only be used for follow-up research. Intravenous urography can well display the renal morphology, and through the displayed renal contour, the thickness of renal parenchyma and the growth of the kidney can be calculated, but on the one hand, ultrasound is more simple and easy to perform.

　　3. Renal radionuclide (DMSA) scan: Can clearly display the condition of renal scars, used for follow-up to determine whether new scars have formed, and can evaluate the function of glomeruli and tubules, determine renal function, and compare renal function before and after surgery.

　　Children with primary vesicoureteral reflux should consume adequate water, at least 3000cc per day, which can be replaced by other liquids such as fruit juices. Try to finish drinking during the day to avoid frequent urination at night. To increase the acidity of urine, consume meat, eggs, cheese, plums, grains, prunes, and dried grapes, and also drink cranberry or red currant juice, and also supplement vitamin C. Children with primary vesicoureteral reflux should avoid spicy and刺激性, cold, and cool foods, and should also avoid smoking and drinking.

　　Since primary vesicoureteral reflux can naturally disappear with growth and development in many children, and reflux without sterile urine does not cause renal damage, the treatment principle for primary vesicoureteral reflux is to control infection, protect renal function, and prevent complications. Drug therapy should be the first choice, even for severe reflux, if the child is young, has good renal function, and has no growth and development disorders, drug therapy should be considered.

　　1. Drug therapy

　　The selected drug should be an antibacterial agent with a broad spectrum, easy to take, inexpensive, with minimal toxicity to children, high concentration in urine, and minimal impact on the normal flora in the body. It should be sufficient to control infection with the minimum dose. Treatment dosage should be used during an infection outbreak, and preventive dosage should be used after the infection is controlled, which should be 1/2 to 1/3 of the treatment dosage to rarely cause adverse reactions. Preventive dosage should be taken before bedtime due to the longest retention time of urine in the body at night, which is more likely to cause infection. The medication should be taken until the reflux disappears. Whether older children with significantly reduced reflux should continue to take preventive antibiotics is currently controversial.

　　2. Regular Follow-up

　　During the period of drug treatment, the child should be followed up regularly, with a physical examination every 3 months, recording height, weight, and blood pressure. Laboratory tests include urinalysis, hemoglobin, white blood cell count, etc., and renal function tests should be performed once a year. These tests should also be adjusted according to the child's condition. To understand whether the urine remains sterile, a urine culture should be performed every 1 to 3 months, and treatment should be adjusted accordingly if the culture is positive. Ultrasound can be used to detect the development of the kidneys and the expansion of the renal pelvis and ureters. Voiding cystourethrography should be repeated 6 months after diagnosis, and then repeated every 6 to 12 months thereafter, and radioactive isotope cystography can also be used for subsequent examinations.

　　3. Injection of Solid Substances

　　Using cystoscopy to inject certain solid substances, such as Teflon or collagen, near the ureteral orifice to prevent urine reflux is a non-surgical treatment method commonly used in Europe and the United States, especially the research on the solid substances used for injection, which has been quite extensive.

　　4. Surgical Treatment

　　The indications for surgical treatment are based on the control of infection and the development of renal function, rather than the degree of reflux. Drug treatment cannot control urinary tract infection or prevent recurrence of infection; surgical treatment should be adopted when there is progressive renal scar expansion or the formation of new scars. Surgery is first considered when there is concurrent vesicoureteral reflux and obstruction, ectopic ureteral orifice, or accompanied by a large ureteral pararenal diverticulum, or when the ureteral orifice is located in the bladder diverticulum.

　　There are various types of antireflux ureterovesical reanastomosis (also known as ureterovesical reimplantation), which are divided into three major categories: extravesical, intravesical, and combined extravesical and intravesical operations. Currently, the more commonly used techniques include Cohen ureterovesical reanastomosis, Politano-Leadbetter ureterovesical reanastomosis, and Glenn-Anderson ureterovesical reanastomosis, etc. The surgery is very mature, with good effects and a success rate of over 95%.