Pediatric vesico-ureteral reflux syndrome
Introduction
Introduction to pediatric bladder-ureteral reflux syndrome Bladder-ureteral reflux syndrome (Vsipoueteral reluxsyndrome, VUR), also known as Iones Williams syndrome, is a syndrome caused by many causes of urine flowing back from the bladder to the ureter or even the renal pelvis, and causing ascending urinary tract infection. basic knowledge The proportion of illness: 0.005% Susceptible people: children Mode of infection: non-infectious Complications: urinary tract infections
Cause
Pediatric bladder-ureteral reflux syndrome etiology
(1) Causes of the disease
The factors causing reflux include congenital reflux factors and acquired reflux factors. They are primary and secondary. The primary ones are congenital fragility of the bladder deltoid muscle and the anatomy of the ureter. Abnormal; secondary is caused by intravesical obstruction, trauma, tuberculosis and non-specific inflammation, inflammation can lead to VUR, but is related to immature development of the bladder deltoid muscle, 45% have urinary tract infection before, 25% have reflux And the big girl only has 20% reflux, reflux can cause kidney, ureteral stagnant water and development stop, the infection is repeated and persistent, can cause renal scar atrophy, and even renal insufficiency, renal hypertension, has been proved in In VUR without bacterial infection, it can cause renal scar atrophy only due to the reflux pressure of urine. Intrarenal reflux, that is, urine from the renal pelvis through the renal nipple, can occur in patients with 5% to 15% VUR. The renal tubules are scattered along the collecting orifice, causing intrarenal inflammation and kidney damage, also known as "reflux nephropathy".
(two) pathogenesis
1. Intrarenal reflux (IRR): can cause renal parenchymal damage. As early as 1965, Brodeur et al reported that among the 18 patients with VUR, there were 5 cases of intrarenal reflux, and when VUR, urine flowed back to the renal pelvis and renal pelvis. The renal pelvis is also countercurrent to the papillary tube and the collecting tubule, so it is also called the renal tubular regurgitation, which is the path of non-obstructive pyelonephritis causing renal parenchymal lesions. Since then, Hodson (1972) in animal experiments. Confirmed by IRR, Rolleston et al (1974) reported that 6.7% of IRR were found in children under 5 years of age, and it was shown in experimental animals that the location of urine from the renal pelvis into the papillary tube coincided with the location of scar formation. Like the scar formed by obstructive pyelonephritis, the two poles of the kidney are the most. Bourne et al. (1976) observed 119 cases of VUR in detail and found that there were 8 cases of IRR (6.7%), and cortical atrophy was seen in the intrarenal countercurrent area. Renal dilatation, these data suggest that IRR can cause renal parenchymal damage.
2. The composite kidney nipple is a countercurrent nipple: Why is countercurrent renal disease more common in the two poles of the kidney? Recent studies have shown that the nipples of the kidney poles are mostly compound nipples, which are formed by the fusion of several kidney leaves or the nipple tube. The opening is large and straight, and it is open to the flat or concave mucosal surface. When the urine in the renal pelvis increases, the opening is invaginated, and urine is likely to flow back into the collecting tube of the nipple tube. The renal nipples of other parts are mostly single nipples, small. In the shape of a cone, the nipple tube is obliquely open to the convex mucosal surface. When the internal pressure of the renal pelvis increases, the orifice is closed. Therefore, it is said that the composite renal nipple is a countercurrent nipple, and the single renal nipple is a non-reflux nipple. .
3. Renal pelvis leaks into the renal parenchyma: Moffat proposes another type of renal damage mechanism of IRR, which is believed to cause rupture of the renal pelvic horn to cause renal pelvis to leak into the renal parenchyma, which is the cause of kidney damage, because the papillary tissue at the iliac crest Covering only a thin layer of epithelium, the epithelium is easily broken when the internal pressure of the renal pelvis increases. This fragile dome is only seen in children under 6 years of age.
4. The mechanism of renal damage proposed by Cotran: The mechanism of renal damage caused by urine reflux is summarized as 5 points: 1 bacteriuria; 2 urodynamic changes; 3 urine leakage into renal tissue; 4 intrarenal vascular stenosis; 5 glomerular sclerosis.
(1) bacteriuria: Ransley observed the condition of renal scar in VUR and IRR in the pig model, and found that in the case of low pressure aseptic and high pressure sterility, no renal scar was produced; hypobaric urinary tract could produce renal scar, and high pressure bacteria Urine produces more scars of the kidney. Therefore, it is suggested that there must be bacteriuria in the VUR and IRR to produce renal scars. The urine reflux only brings the bacteria into the kidney. Kidney tissue damage is a direct consequence of bacterial invasion.
(2) urodynamic changes: IRR does not necessarily exist in VUR, IRR occurs only in severe VUR, because the pressure factor in the renal pelvis is very important, the normal pyelone and renal pelvis hydraulic pressure is 1.33 ~ 2.00kPa ( 10~15mmHg), IRR can occur beyond this range. When the bladder is extremely full or urinating, due to the presence of severe VUR, the renal pelvis, renal pelvis, ureteral pressure and bladder can reach 5.32 kPa (40 mmHg) or more. The IRR occurs, and the bladder is intermittently contracted, causing the countercurrent urine to continuously impact and cause kidney damage.
(3) leakage of urine into the kidney tissue: the bladder urine flows back to the renal pelvis, leaking into the renal interstitium through the rupture of the small tube or the humeral angle, which can directly stimulate or cause inflammation and fibrosis through autoimmune reaction. Urine (not primary urine) is a fibrosis promoter outside the urinary route, so inflammation and fibrotic lesions occur in the urine leakage site. Tamm-Horsfall protein (THP) is the thick segment of the pulp A protein secreted by the distal convoluted tubules is excreted in the urine. The deposition of THP in the renal interstitial can be used as a marker of leakage of urine into the renal interstitial, in tubulointerstitial nephritis, medullary cyst disease, obstruction. Renal interstitial THP deposition in renal nephropathy and reflux nephropathy, indicating that renal interstitial inflammation and fibrosis of these diseases are the result of direct stimulation of urine. The immune response caused by THP in renal tissues is increasingly valued by people. Mice were immunized with THP to produce THP autoantibodies and tubulointerstitial nephritis with granular deposition. The epithelium of the medullary ascending branch was deposited with IgG, C3 and THP. There were lymphocytes, plasma cells and monocytes around the tubules. Neutrophil Infiltration, and considered that these immune complexes are formed in situ, Mayrer et al reported that injection of the same rabbit urine or THP, resulting in interstitial nephritis in rabbits, while demonstrating THP-specific T cell mediators and antibody-dependent cytotoxicity induced this Kidney damage.
(4) Intrarenal vascular stenosis: due to leakage of urine into the interstitial and capillaries and straight blood vessels outside the renal tubules, causing inflammation and fibrosis, leading to renal vascular occlusion and stenosis, further causing intrarenal ischemic lesions and In secondary hypertension, an increase in renin concentration can be measured in renal venous blood.
(5) glomerular sclerosis: In recent years, people have paid attention to the problem of focal segmental glomerulosclerosis caused by VUR. Kincaid-Smith believes that this glomerular sclerosis and focal lesions in nephrotic syndrome Similar to segmental glomerulosclerosis, Cotran summarized the pathogenesis of glomerular sclerosis in this disease as follows: 1 immune damage: It is believed that this glomerular damage is caused by bacteria and its metabolites or autoimmune complexes. The autoantigen may be a brush border-associated antigen or THP. Zimmerman et al. and Nicastri reported that IgM and C3 are granular deposits in the glomerular mesenteric and subendothelial beyond the scar area, and the 2 mesangial cell insufficiency: macromolecular substance After being taken, it leads to incomplete function of mesangial cells. 3 Intrarenal vascular disease: Most patients have intimal hyperplasia of interlobular arteries, middle layer hypertrophy, which may be the main cause of glomerular sclerosis. 4 glomerular hyperfiltration Role: glomerular tissue in the lesion area decreased, intact glomerular kinetics and hardening, animal experiments showed that glomerular sclerosis developed progressively when the nephron was reduced by 75%.
Prevention
Pediatric bladder-ureteral reflux syndrome prevention
Urinary tract infection plays an important role in the pathogenesis of this disease. Therefore, it is important to actively prevent urinary tract infections, prevent urine reflux, prevent the occurrence and progression of renal damage, and anti-reflux surgery has been used in clinical practice for more than 30 years, due to PVUR. As the age increases and gradually disappears or is alleviated, the surgical indications should be strictly limited. Willscher et al believe that it only applies to:
1VUR persists and is still re-infected with antibiotics.
2 severe VUR with infection, in recent years using endoscopic injection of teflon treatment, achieved good results, Normand and Smellie that ureteral implantation can not improve its prognosis, Torres et al observed the results of surgery and non-surgical patients, think There is no difference in the time from diagnosis to renal failure. In recent years, most scholars have advocated strict control of infection, waiting for VUR to disappear or reduce itself. Strictly control infection in children with VUR. After 10 years of observation, it is rare to find scar formation and progress in the kidney. Renal dysfunction.
Complication
Pediatric bladder-ureteral reflux syndrome complications Complications, urinary tract infection, hypertension
Repeated urinary tract infection, advanced hypertension and renal insufficiency, reflux can cause kidney, ureteral stagnant water and development stop, infection persists persistently, can cause renal scar atrophy, and even renal insufficiency, renal hypertension, etc. .
Symptom
Pediatric bladder-ureteral reflux syndrome symptoms common symptoms renal damage urinary tract infection chronic renal insufficiency glomerular sclerosis chills bladder irritation renal failure proteinuria bladder residual urine volume increased urgency
There are no special symptoms in children with reflux. The symptoms of older children are more obvious. Before the age of 3, the number of boys is more than that of girls. After 3 years of age, the incidence of girls is more common. It may be related to the increased chance of urinary tract infection. The symptoms of bladder irritation are only in Inflammation in the acute phase, fever, chills, frequent urination, urgency, low back pain, common in patients with pyelonephritis, simple reflux due to increased residual urine volume of the bladder, visible increase in urine, urinating after the next urination still more urine Amount, urinary dripping, post-urd wet pants, urine odor, common enuresis in older children as the first diagnosis, 21% of children have a history of enuresis, bladder fullness or urination when feeling low back pain, but also see severe reflux Those with no obvious symptoms, those with simple reflux and high blood pressure are rare, proteinuria reflects renal parenchymal damage, and 20% of children with massive proteinuria may develop renal insufficiency within 3 to 4 years. The proteinuria is mainly glomerular. Sexual proteinuria, 15% to 30% of children eventually develop renal failure, and continuous reflux can lead to growth and development disorders in children.
1. Reflux and urinary tract infections
The persistence of reflux often causes urinary tract infections to prolong and recur, urinary tract infections prolong, inflammatory changes can change the anatomical structure of the ureteral bladder junction, lose the valve effect and make the reflux worse and difficult to eliminate, recurrent urinary tract infection With reflux more often than no recurrence, pyelonephritis with reflux is more prone to renal reflux and kidney damage, P-fimbriated E. coli infection causes pyelonephritis, due to easy Combined with urethral epithelial cells to weaken the peristaltic function of the ureter, it is more prone to reflux. After infection control, primary reflux can be gradually eliminated. There is no urinary tract infection and the ureteral opening is normal. 65% of the children are within 5 to 6 years. Reverse flow elimination.
2. Kidney scar
Renal scarring is a focal or diffuse irreversible renal parenchymal damage. The formation of renal scar is related to the anatomical features of the kidney nipple. Intrarenal reflux often occurs in the kidney, the lower nipple, nipple The opening of the tube is large, the nipple is wide and flat, and when the pressure is high, the reflux is easy to occur, and the countercurrent pressure during reflux is significantly increased. The average pressure during the filling period of the bladder is 3.07 to 3.60 kPa, and the pressure during the bladder contraction and urination during reflux can be increased. Above 10.7 kPa, the kidney tissue is compressed to form scars. The neonatal and early childhood kidney tissue is not well developed. Mild reflux can also form scars. The incidence of mild reflux renal scars is 20% to 35%, and severe reflux Up to 79%, kidney scars occur before the age of 5, kidney scar can also occur after pyelonephritis infection without reflux, renal scar continues to adult, its pathology eventually develops to glomerular pericytes, glomeruli Hardening and renal atrophy, according to renal morphology changes renal scar can be divided into 4 phases: Stage I: only one scar on the kidney or lower pole, stage II: more than 2 scars, stage III: scar enlargement, kidney atrophy, Stage IV Gu Shen, small kidney, staging conducive to determine the condition and prognosis.
3. Reflux nephropathy
Reflux nephropathy is caused by reflux to the kidney and causes renal parenchymal damage, eventually developing chronic renal insufficiency. The incidence of reflux nephropathy is as high as 43% in adults, and only 10% to 24% in children. The severity of reflux can be 5 months to 28 years after diagnosis. It is more common in secondary reflux. Kidney sputum nephritis with renal reflux is prone to kidney damage. The hydraulic increase of urinary reflux can cause renal tubular rupture and kidney. Fibrosis, renal atrophy, bacteria can enter the renal interstitial with fluid to cause interstitial inflammation, high-pressure aseptic intrarenal reflux can also occur renal damage, a large number of exfoliated renal tubular epithelial cells, more abnormal red blood cells and cells Tubular type, suggesting that severe intrarenal reflux has caused renal tubular and glomerular damage, and the pathological changes are focal segmental glomerular sclerosis. If the reflux continues to adulthood, 5% to 10% develop to the end stage. Renal failure, the cause of renal damage is related to the secretion of renal distal convoluted tubules, the synthetic Tamm-Horsfall protein, the self-destructive renal tubules infiltrate into the renal interstitial, causing the immune barrier to destroy and produce an antibody response. The protein in the tubulointerstitial Deposition week Visible mononuclear infiltration of macrophages, CD8 lymphocyte percentage increased, CD4 / CD8 lymphocyte ratio was significantly decreased, showing the immune response is an important factor leading to kidney damage reflux.
Examine
Pediatric bladder-ureteral reflux syndrome examination
1. Urine test
Urine routine examination may have protein, red blood cells, pyuria, hematuria may also occur, urine routine light microscopy or electron microscopy scan if tubelet epithelial cells and abnormal red blood cells increase should consider the presence of reflux nephropathy, proteinuria can be used as reflux nephropathy patients The first symptom, urine microprotein determination (including urine 2-microglobulin, 1-microglobulin, retinol-binding protein, urinary albumin) and urine N-acetyl--glucosaminidase (NAG) quantitative discharge increased, It is helpful for the diagnosis of early reflux nephropathy and renal scar formation. The decrease of urinary Tamm-Horsfall protein reflects renal tubular dysfunction, chronic pyelonephritis, and chronic renal parenchymal lesions are significantly reduced, and pathogenic bacteria can be found in mid-stage urine culture. The colony count is also abnormal.
2. Glomerular filtration rate
Severe renal damage showed a decrease in glomerular filtration rate.
3. Ultrasound examination
Real-time B-ultrasound examination is suitable for diagnosing reflux sifting. If you see ureter, pyelectasis should be considered for reflux. Now you can use color Doppler ultrasound to observe the reflux after urinary bladder filling. The position of the ureteral opening can be observed, which is beneficial for early diagnosis, safe method and no pain.
4. Urinary bladder urethrography (MCU)
Because it can be classified according to the degree of reflux, it is more commonly used X-ray diagnosis method. 15%-20% diatrizoate 100-150ml is injected into the bladder after catheterization, so that children can urinate, or 30% of the above contrast agent 30 ~50ml into the bladder followed by 10% diatrizoate 150 ~ 200ml bottle infusion, the height of the bottle should not be greater than 70cm on the bladder level, the contrast dose can make the bladder full to a slight discomfort, visible in the presence of reflux The contrast agent is countercurrent to the ureter. If no reflux occurs, the sick child can urinate and observe the presence of reflux. To prevent the ascending infection, antibiotics should be used to control the acute infection before the contrast. The degree of reflux can be based on international reflux. The International Reflux Study (IRS) is divided into 5 degrees:
I degree: reflux only reaches the ureter.
II degree: reflux to the renal pelvis, renal pelvis, but no expansion.
III degree: ureteral light, moderately dilated or tortuous, renal pelvis light, moderately dilated, but no or mild tonic blunt.
IV degree: moderate expansion or distortion of the ureter, renal pelvis, moderate expansion of the renal pelvis, complete disappearance of the humerus, but maintain the shape of the nipple.
V degree: The ureter is obviously distorted, the renal pelvis and the renal pelvis are significantly dilated, but most of the renal pelvis loses the shape of the nipple.
Clinically, the classification of reflux, below III degree is mild reflux, above IV degree is severe reflux, determining reflux index, which is conducive to disease estimation and prognosis judgment, and can take effective treatment measures.
5. Intravenous urography (IVU)
This method can determine the presence or absence of kidney damage, such as kidney size, morphology, developmental malformations, if the ureter and renal pelvis expansion, should consider the presence of reflux, the use of large doses of IVU plus tomograms easier to determine renal scars, see renal cortical thinning , depression, kidney outline jagged, such as renal pelvis expansion, renal pelvis is drumstick deformation, renal scar formation, renal atrophy should consider the presence of reflux nephropathy, but early diagnosis of mild reflux is easy to miss, the degree is also certain Difficulties, in recent years, the use of contrast agents completely discharged to the bladder, allowing patients to urinate to observe the presence of reflux, but the time needs to be 3 to 4 hours, young children are not easy to cooperate, its advantages can avoid the pain of retrograde intubation,
Recently, it has been proposed to perform both IVP and VCG tests regardless of gender, age, and initial onset.
6. Nuclide check
The radionuclide examination showed that the radiation dose was lower than that of the MCU. Indirect or direct urinary nucleus bladder urinary tract imaging was used. Indirect intravenous injection of 99mTc-DTPA 35mCi was used to observe the urinary reflux after the bladder was filled. Single photon emission computed tomography (SPECT) can eliminate intubation pain, simple method, can understand kidney function, effective renal blood flow and renal imaging, but the reflux index is not as clear as MCU, urinating When children need to cooperate, the direct method is to inject 99mTC-DTPA 1mCi into the catheter and then inject the normal saline. After the bladder is full, the results are consistent with the MCU method, but the renal insufficiency affects the result and occasionally false positive.
In recent years, 99mTC-DMSA imaging has been used to detect reflux nephropathy. The sensitivity and specificity of renal scar and renal function are better than intravenous urography.
Diagnosis
Diagnosis and diagnosis of bladder-ureteral reflux syndrome in children
Clinical manifestations are often recurrent and difficult to control urinary tract infections, abnormal urination such as polyuria, urinary dripping, enuresis, urine routine examination may have protein, red blood cells, pyuria, hematuria may also occur, middle-stage urine culture can find pathogenic bacteria, The above characteristics should consider whether there is the possibility of this disease, abnormal venous pyelography (IVP), according to the degree of reflux, classification (see auxiliary examination) diagnosis, urinary bladder angiography (VCG) examination is generally in the IVP examination 1 ~ It will be carried out after 2 weeks.
This disease should pay attention to the primary and secondary reflux phase differentiation, the primary is caused by congenital vesicoureteral dysfunction, the most common, secondary and urinary tract infection, trauma, bladder neck and lower urinary tract obstruction, Pregnancy and other related, pay attention to the history and related clinical manifestations to help identify, the common clinical manifestations of this disease are repeated fever, abdominal pain, dysplasia and gross hematuria, etc., should be differentiated from other causes of infection, abdominal pain, dysplasia and hematuria and other diseases .
