Vesicoureteral reflux and reflux nephropathy in children

　　Vesicoureteral reflux in children refers to the backflow of urine from the bladder to the ureter and renal pelvis during urination. Reflux nephropathy is a syndrome caused by vesicoureteral reflux, intrarenal reflux, and recurrent urinary tract infections, leading to kidney scarring, atrophy, and abnormal renal function. If not treated and corrected in time, it can develop into chronic renal failure. Vesicoureteral reflux not only occurs in children but also persists into adulthood on the basis of recurrent UTI, leading to renal function damage. A large amount of data shows that RN is one of the important causes of end-stage renal disease.

　　The causes of vesicoureteral reflux in children:

　　The main mechanism causing vesicoureteral reflux in children is the abnormality of the vesicoureteral junction. According to the cause of occurrence, it can be divided into the following two categories:

　　1. Primary

　　The most common cause is congenital incomplete vesicoureteral valve mechanism, including congenital short or horizontal ureteral submucosa, abnormal ureteral orifice, thin and weak trigone muscle tissue of the bladder, congenital abnormality of Waldeyer's sheath, and others. 53% of the cases are due to vesical detrusor dysfunction causing reflux.

　　2. Secondary

　　Factors causing dysfunction of the Waldeyer's sheath include UTI, bladder neck and lower urinary tract obstruction, trauma, pregnancy, etc. Up to 30% to 50% of children with UTI have concurrent reflux. During UTI, the vesicoureteral segment may lose its normal valve function due to inflammation, swelling, deformation. The main pathogenic bacteria in UTI, such as Escherichia coli, are prone to bind with uroepithelial cells and weaken the peristaltic function of the ureter, causing reflux. After controlling the infection, reflux can gradually disappear. If it recurs and persists, it is difficult to eliminate. Urinary tract anomalies with reflux account for about 40% to 70%. In addition, bladder ureteral dysfunction, such as primary spinal cord closure defect, including meningomyelocele, etc., about 19% of cases have vesicoureteral reflux in children.

　　Vesicoureteral reflux (VUR) in children refers to the reflux of urine from the bladder back into the ureter and pelvis during urination. Reflux nephropathy is a syndrome caused by vesicoureteral reflux and intrarenal reflux accompanied by recurrent urinary tract infections, leading to kidney scarring, atrophy, and abnormal renal function. If not treated and corrected in time, it can develop into chronic renal failure. Common complications include the following:

　　1. Renal scarring

　　The presence of vesicoureteral reflux (VUR) in children increases the risk of kidney involvement in urinary tract infections, and the possibility of kidney scarring also increases as a result.

　　2. Hypertension

　　Reflux nephropathy is one of the most common diseases leading to hypertension in children, with a prevalence of hypertension in VUR children as high as 20%. The pathogenesis may be related to the renin-angiotensin system and Na+/K+ ATPase activity. It is difficult to predict the risk factors for the occurrence of hypertension, so regular follow-up is still the only method to identify hypertension populations at present. The measurement of plasma renin cannot predict the occurrence of hypertension.

　　3. Chronic renal failure

　　VUR and the resulting reflux nephropathy lead to the occurrence of chronic renal failure. The incidence of end-stage renal disease (ESRD) secondary to reflux nephropathy in the United States is 5.7-22%, and in New Zealand, reflux nephropathy accounts for 11.3% of dialysis patients. In the past decade, due to increased awareness and treatment of VUR, the incidence of terminal reflux nephropathy has decreased significantly.

　　Infants and young children often present with non-specific symptoms of urinary tract infection and reflux, including fever, fatigue, drowsiness, anorexia, nausea, vomiting, and delayed growth and development; they may also experience renal colic and tenderness in the renal area; if secondary infection occurs, symptoms such as frequent urination, urgency, and dysuria may appear; in severe infections, purulent urine may occur; occasionally, after exertion, there may be soreness; those with renal scarring may seek medical attention due to hypertension, and the most serious consequence is the development of pyelonephritic scarring, leading to secondary hypertension and chronic renal insufficiency. During physical examination, in addition to palpable enlarged kidneys, occasionally palpable thickened ureters may be felt, and there may be mild percussion tenderness in the renal area. In patients with bilateral vesicoureteral reflux, symptoms of renal insufficiency may be present.

　　The prevention and treatment of vesicoureteral reflux in children mainly focus on preventing and controlling the occurrence and progression of renal damage, with the most important being to stop urinary reflux and control infection.

　　Due to the lack of effective treatment for reflux nephropathy, if there is any suspicion of the disease, it is advisable to go to a well-equipped hospital for early diagnosis and treatment, control infection, hypertension, and proteinuria. When renal insufficiency occurs, a high-quality low-protein diet can delay the onset of end-stage renal failure.

　　Since the symptoms of clinical diagnosis of vesicoureteral reflux (VUR) are often not obvious or only have non-specific manifestations, diagnosis depends on imaging studies. Common examinations include:

　　Laboratory examination

　　Routine urinalysis by light microscopy or electron microscopy: If there is an increase in tubular epithelial cells and atypical red blood cells, consider the presence of reflux nephropathy. Proteinuria can be the initial symptom of a patient with 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 the formation of renal scars; decreased glomerular filtration rate indicates severe renal damage. Decreased amount of urinary Tamm-Horsfall protein reflects tubular dysfunction, and there is a significant decrease in chronic pyelonephritis and chronic renal parenchymal lesions.

　　Other auxiliary examinations

　　1. Ultrasound examination: Real-time B-ultrasound is suitable for screening for the diagnosis of reflux. If there is dilation of the ureter and renal pelvis, consider the presence of reflux. Now, color Doppler ultrasound is used to observe the reflux condition during micturition after the bladder is filled, and to observe the position of the ureteral orifice, which is beneficial for early diagnosis. The method is safe and painless.

　　2. Radionuclide cystography can accurately determine whether there is reflux, but it is not precise enough to determine the degree of reflux and can only be used for follow-up studies. Intravenous urography can well display the shape of the kidneys, and through the displayed renal outline, the thickness of the renal parenchyma and the growth of the kidney can be calculated. However, on the one hand, ultrasound is simpler and more feasible.

　　3. Renal radionuclide (DMSA) scanning can clearly show the condition of renal scars, used for follow-up to determine if new scars have formed, and can evaluate the function of glomeruli and renal tubules, determine the function of each kidney, and compare renal function before and after surgery.

　　Children with vesicoureteral reflux and reflux nephropathy should pay attention to dietary intake of foods such as pork kidneys, chives, walnuts, and nuts, drink plenty of water, reduce alcohol consumption, and engage in moderate exercise. They can also perform waist massage. Dietary taboos are as follows:

　　1. Low purine

　　Due to the metabolic burden of a large amount of purines in the body, especially for patients with gout, a high-purine diet can trigger gout attacks and worsen the condition of gout. Vegetables like celery and spinach, peanuts, chicken soup, various meat soups, pork head meat, sardines, and animal internal organs all contain a large amount of purines, so they should be strictly limited. Purines are also present in lean meat, and when eating, the meat can be boiled in water first, and the soup discarded before consumption.

　　2. Supplement vitamins

　　Intake of sufficient vitamins and trace elements. Vitamin B, vitamin C, and zinc, calcium, iron, etc., can play a protective role for the kidneys.

　　3. Appropriate Diet of High Fiber Diet

　　High fiber is beneficial for maintaining smooth bowel movements, toxin excretion, and maintaining human metabolic balance. Patients with kidney disease should eat more coarse grains, such as corn flour, buckwheat flour, taro, seaweed strips, certain fruits and vegetables, etc.

　　Ureterovesical reflux is divided into primary and secondary types. The former is due to congenital maldevelopment of the valve function, and the latter is secondary to lower urinary tract obstruction, such as posterior urethral valves, neurogenic bladder, etc. Ureterovesical reflux is closely related to urinary tract infection and renal scarring, and reflux can lead to hypertension and renal failure. The main treatment of this disease is to stop urine reflux and control infection to prevent further damage to renal function.

　　1. Medical Treatment

　　Medical treatment measures are adopted according to the different grades of VUR.

　　(1) Grades I and II: Treat infections and take long-term medication for prevention. SMZCo can be used for treatment, with a dosage of 5~10mg/Kg of SMZ and 1~2mg/kg of TMP, taken at bedtime for one year or more. Prevention of infection is effective, and urine culture should be performed once every 3 months, and radionuclide examination or voiding cystography should be performed annually to observe the degree of reflux. After the reflux disappears, urine culture should still be performed every 3-6 months because reflux can sometimes be intermittent. In addition, it is encouraged to drink plenty of water, urinate twice before bedtime to reduce intravesical pressure, maintain regular bowel movements, and defecate on time.

　　(2) Grade III: The treatment is the same as grades I and II, but reflux should be checked every 6 months, and intravenous pyelography should be performed annually.

　　(3) Grades IV and V: Surgery should be corrected after preventive medication.

　　2. Surgical Treatment

　　The surgical treatment methods for VUR are mostly plastic surgery. The indications for surgery are:

　　①Above grade IV reflux;

　　②For patients with grades III and below, initial medical observation and treatment should be given, and surgery should be performed if there is persistent reflux and the formation of new scars;

　　③Repeated urinary tract infections that have not improved after 6 months of active treatment;

　　④And there are urinary tract obstructions.

　　Currently, injection therapy is popular abroad, which only requires short-term anesthesia and can be treated on an outpatient basis or without hospitalization, making it easy for parents to accept.