Chronic reflux nephropathy

　　1. Etiology

　　The cause of reflux nephropathy is vesicoureteral reflux. Vesicoureteral reflux is the reflux of urine through an incomplete vesicoureteral junction. Under normal physiological conditions, the complete anatomical function of the flap mechanism of the last segment of the ureter can prevent this reflux. This flap mechanism includes: the oblique passage of the ureter through the bladder wall; the special muscle tissue of the ureter wall; the mucosal flap at the ureteral orifice. The change in the anatomical function of the aforementioned flap mechanism will lead to primary or secondary VUR.

　　1. Primary vesicoureteral reflux:Primary VUR is the most common clinical type, mostly seen in children, and is a congenital anomaly of the submucosal ureteral segment of the bladder, such as congenital shortening of the submucosal ureter of the bladder, underdeveloped trigone muscle tissue, etc. As children grow up, the development of the bladder base is perfect, and most reflux will disappear.

　　It is widely believed that primary reflux is mostly due to congenital defects in the length, diameter, muscle tissue, or innervation of the submucosal part of the ureter under the bladder mucosa. It may be very important that the submucosal part of the ureter is too short due to ectopic location of the ureteral orifice. When the bladder is full, the submucosal part of the ureter may further shorten and cause reflux, which is consistent with the observation that reflux only occurs when the bladder is full or during micturition.

　　Primary VUR has a significant tendency to self-heal before puberty. Patients with mild reflux (I-II level) without ureteral dilation have nearly 75% to 85% of reflux cessation, and patients with moderate reflux have 66% of reflux disappearance. Patients with more severe reflux (III-V level) with ureteral dilation have nearly 25% to 30% of reflux cessation. Woodard believes that the mechanism is that the intramural segment of the ureter elongates with age. Heale's research shows that 98% of infants with mild and moderate reflux are normal within three years, and 25% of infants with severe reflux remain normal for a longer period. Robert's report confirms that the duration of primary severe reflux is longer than that of moderate reflux.

　　The familial tendency of VUR is 8% to 32%. Compared with sporadic cases, familial cases of VUR are more severe and more often bilateral. The results of the human leukocyte antigen (HLA) examination of 43 Greek children with VUR showed that children carrying HLA-Aw1929 have a higher incidence of the disease.

　　Research shows that in 1/20 of patients with reflux, reflux is related to urinary tract obstruction. In cases of mild reflux, concurrent obstruction is often easily diagnosed; in cases with dilated and/or twisted ureters, an unevenly dilated renal pelvis suggests the possibility of obstruction. There are reports that in 147 patients with VUR, 17 (14%) had concurrent obstruction at the ureteropelvic junction. Some scholars suggest that children considered to have ureteropelvic junction obstruction should undergo routine voiding cystourethrography.

　　Bisset studied the incidence of VUR in patients with urinary tract duplications, and the results showed that 69% of patients with complete urinary tract duplications and 22% of patients with partial urinary tract duplications had VUR.

　　2. Secondary vesicoureteral reflux:Secondary VUR can be secondary to various causes of bladder neck or urethral obstruction (bladder hypertension), neurogenic bladder (bladder muscle weakness), bladder tuberculosis, and postoperative bladder surgery (causing ureteral injury). Common secondary conditions include the following:

　　(1) Ureteral diverticula: Some studies suggest that the formation of ureteral diverticula due to unstable bladder contractions and high-pressure micturition, as well as local congenital weakness of the ureter, plays an important role in the occurrence of VUR.

　　(2) Non-neurogenic neurogenic bladder syndrome (nonneurotic neurogenic bladder syndrome): This is a mental and behavioral disorder symptom that manifests as bladder sphincter dyssynergia in clinical and radiological terms, and a functional obstruction of the bladder seen in children without anatomical and neurological abnormalities. This syndrome often presents with bedwetting, discontinuous micturition, characteristic micturition posture, recurrent lower urinary tract infections, and changes in bladder morphology. Urodynamic examination shows hyperreflexia of the bladder and difficulty in coordination between the detrusor and sphincter. This pathological mechanism is related to the so-called 'primary' vesicoureteral reflux and its persistence. In most cases, the hyperactive detrusor state disappears after the development of the nervous system matures.

　　(3) Abnormalities of lower urinary tract function: There are two types of urinary dynamics with opposite reflux dysfunction, without neurological or gross anatomical abnormalities. The first type has reflux but the bladder has strong voiding contraction stability, and reflux often appears unilaterally, with rare reflux nephropathy or upper urinary tract abnormalities. The second type is common during micturition, with bladder contraction weakness and overactive urethral closure mechanism, and reflux often appears bilaterally, with quite common reflux nephropathy or upper urinary tract abnormalities.

　　(4) Constipation: Constipation causes rectal distension, which leads to dyscoordination of the perineal detrusor, distortion of the trigone, and abnormal function of the ureteral valves, which may cause urinary tract infection, enuresis, and VUR.

　　(5) Inflammatory diseases involving the bladder ureteral junction: Secondary VUR also occurs in inflammatory diseases involving the bladder ureteral junction, such as tuberculosis and schistosomiasis. If bladder inflammation does not damage the submucosal segment of the ureter, VUR generally does not occur.

　　(6) Bladder neck lesions: Obstruction of the bladder neck, radiotherapy to the bladder, and other congenital anomalies may cause VUR.

　　(7) Neoplasms.

　　(8) Removal of urinary tract catheters: There have been reports of VUR occurring in 2 patients after ureteroscopy.

　　(9) Posture valve: Children with a urethral posterior valve have nearly half with severe bladder-renal reflux, 53% of all cases have decreased renal function, and the incidence of bilateral VUR is 25%.

　　(10) Congenital or acquired neurological diseases: The incidence of VUR is higher in congenital or acquired neurological diseases. In children with meningocele, the incidence of reflux increases with age, from 28% at one month to 45% at 5 years. In cases of spinal dysraphism, the incidence of VUR is 36% to 52%. Follow-up reports of spinal cord injury for more than 8 years show that 10% of cases have radiological manifestations of VUR, and reflux is found from 4 to 24 months after injury. In Alzheimer's disease with astrocyte degeneration, accompanied by neurogenic bowel and neuropathic bladder, multiple refluxes can coexist, including buccal saliva reflux, gastroesophageal reflux, vesicoureteral reflux, prostatic urethral reflux, and urethral bladder reflux.

　　(11) Cystitis: It has been reported that VUR can occur in patients with cystitis caused by cyclophosphamide, accounting for 39%, and 17% have hydronephrosis, 13% of patients have bladder fibrosis contraction.

　　(12) Renal transplantation: It has been reported that 29% of transplanted kidneys have pelvis-renal reflux 3 days after surgery, nearly half of the transplanted kidneys with reflux fail, while only 16% of the transplanted kidneys without reflux fail. The progression of renal failure related to reflux is slow, and it is related to increased proteinuria, microscopic hematuria, hypertension, and mesangiocapillary glomerulonephritis.

　　3. Classification of vesicoureteral reflux:Currently, the widely accepted standard is the reflux degree grading standard proposed by the International Children's Bladder Ureteral Reflux Study Group:

　　Grade I: Only involves the ureter.

　　Grade II: Involves the ureter and pelvis, the calyces are not expanded, and the renal papillary dome is normal.

　　Grade III: Mild to moderate expansion and (or) curvature of the ureter, mild to moderate expansion of the pelvis, the dome is without or only slightly钝.

　　Grade IV: Moderate expansion and (or) curvature of the ureter, moderate expansion of the pelvis and calyces, the acuteness of the dome angle disappears, but the shape of most renal papillae exists.

　　Grade V: Severe expansion and curvature of the ureter, pelvis, and calyces, with the shape of most renal papillae disappearing.

　　Second, pathogenesis

　　The exact pathogenesis of RN has not been fully elucidated. Renal damage caused by urinary reflux may be related to several factors:

　　1. The role of urinary tract infection in the pathogenesis of reflux nephropathy (RN):Urethritis is one of the important risk factors for scar formation; VUR is an important mechanism that allows bacteria to enter the kidney from the infected bladder. UTI is often closely related to RN, with 15% to 60% of infants and children with UTI having some degree of reflux. Among pregnant women found to have potential bacteriuria, 5% to 33% have urinary tract abnormalities, the most common of which is VUR. 4% to 5% of patients with recurrent symptomatic UTI have reflux nephropathy.

　　Reflux leads to an increased incidence of pyelonephritis when causing UTI. Literature reports that in patients with reflux, pyelonephritis is seen in 82% of UTIs. In children with VUR and UTI who have received renal transplantation, the incidence of pyelonephritis is also significantly increased. Experimental studies have shown that in severe reflux, there may be aseptic interstitial nephritis in the renal cortex, similar to chronic pyelonephritis. Infection exacerbates the aseptic interstitial inflammation, which can cause severe lesions even in mild reflux. Clinically, when patients with this disease have an infection, their renal function rapidly deteriorates, and their renal function improves after antibiotic treatment.

　　2. Relationship between VUR and renal scars:VUR causes intrarenal reflux (IRR), and the location of IRR is where the scars form later. In VUR patients, 15% to 73% of them have renal scars. The occurrence of IRR and renal scars caused by VUR can be affected by some factors, such as:

　　(1) Age: It was previously thought that most renal scars were formed before 5 years of age, but now it has been found that many patients are older than 5 years, and even over 10 years old can form scars.

　　(2) Urinary tract infection: The formation of renal scars is often the result of VUR combined with infection and intrarenal reflux.

　　(3) Severity of VUR: The more severe the reflux and the longer the duration, the higher the incidence of renal scars. Generally, 1, 2, and 3-grade VURs rarely cause RN, while 4 and 5-grade VURs almost always cause RN.

　　(4) Type of renal papillae: Renal scars are mainly distributed in the renal pole area, most commonly in the renal pole, which is mainly because the renal pole area is mostly compound papillae,呈扁平型, with large and straight orifices, which are very prone to produce IRR.

　　(5) Those with old scars are prone to form new scars.

　　3. Non-infectious renal damage during VUR:There are reports showing that some reflux nephropathy appears as non-infectious renal damage when VUR occurs without a history of UTI. About half of the reflux nephropathy reported in some literature has no history of UTI. The pathogenesis of non-infectious renal damage during VUR is related to many factors.

　　(1) Intrarenal reflux: In recent years, it has been recognized that the importance of renal pelvis tubular reflux, renal papillary structural characteristics, and the lack of an effective anti-reflux mechanism in the pathogenesis of RN. Ransley and Risdon reported two types of renal papillae: compound renal papillae and single renal papillae. The former drains multiple lobes, and its orifice is round and open at high pressure. The orifice of the single renal papillae opens towards the convex surface, and closes when the pressure increases to prevent intrarenal reflux. The ratio of compound renal papillae to single renal papillae is 1:4, and most compound renal papillae are located at the renal pole III. Tamminen and Kaprio found that 2/3 of the renal papillae in infants and children have no convex surface, and the orifices have expanded vestibules, which are the types of papillae that allow intrarenal reflux. The pressure for renal pelvis-renal reflux in normal kidneys is 80-100 mmHg, while renal intrarenal reflux can occur at lower pressure. Cystoureterography shows that 13 of the 20 renal intrarenal reflux kidneys have reflux nephropathy. In addition, urinary dynamics changes can also cause renal damage due to IRR.

　　(2) Ischemia caused by vascular damage secondary to hypertension.

　　(3) Ischemia caused by vascular damage secondary to hypertension.

　　(4) The direct effect of hydrostatic pressure.

　　(5) Tamm-Horsfall protein and other components in the urine enter the interstitium, causing fibrosis and changes in the perivascular space, leading to secondary ischemic lesions.

　　(6) Immune injury: the antigen may be bacteria in the refluxed urine or Tamm-Horsfall protein. There have been reports suggesting that the immune response caused by the latter plays an important role in the pathogenesis of RN.

　　(7) Secondary residual kidney due to hyperfiltration of focal segmental glomerulosclerosis, which is common in patients with bilateral kidney involvement, functional impairment, and proteinuria exceeding 1g/d.

　　The late-stage common complication of RN is hypertension, with an incidence rate of 10.6% to 38.1%; some cases may be asymptomatic for a long time, gradually developing into late-stage renal insufficiency and entering the uremia stage.

　　1, Urinary tract infection:Frequent urination, urgency, dysuria, and fever, which may manifest as typical acute pyelonephritis in severe cases;

　　2, Hypertension:It is a common complication in the later stage and is also the most common cause of malignant hypertension in children;

　　3, Proteinuria:More common in male patients, although not severe, it indicates that it has developed to intrarenal reflux;

　　4, End-stage renal failure:Reflux nephropathy is one of the main causes of end-stage renal failure in children.

　　The clinical manifestations of this disease vary. The frequency of urinary tract infection episodes and the severity of symptoms are not related to the degree of reflux and renal scarring. Cases with only one infection history can also have severe reflux. Children often develop the first urinary tract infection before the age of 4, and are usually seen for recurrent urinary infections. Most internal medicine patients are middle-aged and young women, and they often come to the hospital due to unilateral renal atrophy, renal failure, urinary infection symptoms, hypertension, etc.

　　The most common clinical manifestations of this disease are urinary tract infection and flank pain that often occurs during urination. The incidence of urinary tract infection is 63% to 88%; the incidence of proteinuria is 34.5% to 54.7%, which can also be the initial symptom of RN. As it often appears several years after severe scarring, it indicates that VUR has already caused glomerular lesions, which is an adverse prognostic sign. Even if VUR disappears after surgery, renal function continues to deteriorate. Additionally, this disease has a latent characteristic, often discovered for the first time during pregnancy due to urinary tract infection, proteinuria, hypertension, pre-eclampsia, or renal failure. Some patients are occasionally found to have unilateral or bilateral renal scarring or atrophy or considered for this disease due to asymptomatic bacteriuria after other reasons for imaging examinations. Some cases may be asymptomatic for a long time, until renal insufficiency enters the uremia stage for diagnosis.

　　Hypertension is common during the course of the disease, with 75% of patients starting dialysis having hypertension. Hypertension can also occur several years after successful anti-reflux surgery. The severity of hypertension is not significantly related to the degree of reflux and the degree of urinary tract obstruction. The incidence of hypertension in clinical practice is 10.6% to 38.1%, and it is a common late complication of RN; gestational hypertension (pregnancy-induced hypertension) can be the initial symptom of RN. About 4% of severe pregnancy-induced hypertension patients have RN; there may be nocturia, polyuria, abnormal urine concentrating function; 10.2% to 50% of RN can lead to renal failure, and the age at onset of renal failure is generally below 35 years old. About half of the cases have azotemia when they seek medical attention. Renal failure in unilateral reflux nephropathy is due to concurrent glomerular lesions in both kidneys. The disease may also have enuresis history (4% to 20%), renal calculi (2.2% to 18%), microscopic or gross hematuria, etc.

　　1. To prevent urinary tract infection, it is important to empty the bladder regularly, especially for two voidings (the second voiding within 5 minutes); long-term low-dose antibacterial therapy is the most commonly used treatment, taking half a tablet of sulfamethoxazole/trimethoprim (bismuth subgallate) before going to bed after urination, and taking it continuously for 6 months, then stopping the medication and observing. If urinary tract infection recurs, the treatment should be restarted. The course of treatment is 1 to 2 years, and for those allergic to sulfonamides, trimethoprim (trimethoprim) can be used alone. Quinolone drugs can also be used, such as ofloxacin (fluoroquinolone).

　　2. To prevent dehydration, adequate water intake should be ensured. Because these patients cannot excrete concentrated urine, they are very prone to dehydration in clinical practice; in addition, drinking more water can reduce the hypertonic state of the renal medulla, which is conducive to controlling infection.

　　3. Prognostic studies have shown that the prognosis of reflux nephropathy is closely related to proteinuria, focal segmental glomerulosclerosis, and progressive renal function impairment. The degree of proteinuria is significantly correlated with the presence and severity of glomerular injury. Progressive glomerulosclerosis is the main determinant of the occurrence of chronic renal failure in reflux nephropathy.

　　Reflux nephropathy is a disease caused by various etiologies. Prevention should start with the prevention and treatment of primary diseases. For diseases that are prone to cause reflux, careful examination, clear diagnosis, and active symptomatic treatment should be carried out to prevent the occurrence and progression of reflux nephropathy.

　　1. Urine examination:In urinary tract infection, sediment examination shows leukocyteuria or pyuria, positive urine bacterial culture; urine may show leukocytes, red blood cell casts, as well as tubular proteinuria, microscopic hematuria, significant decrease in urine specific gravity and urine osmolality, and other manifestations of renal damage. Elevated NAG enzyme in urine, elevated β2-m in urine, decreased concentrating function, and reduced reabsorption of β2 microglobulin suggest tubular dysfunction. Proteinuria exceeding 1g/d suggests secondary focal segmental glomerulosclerosis in this disease.

　　2. Blood examination:Visible blood leukocyte count elevation, left shift of the nucleus, and systemic infectious symptoms, positive Tamm-Hosfall antibody, elevated IgG, azotemia and elevated blood creatinine levels may occur when acute renal function impairment occurs, and hypernatremia may appear when the concentrating ability decreases.

　　3. Renal biopsy:The pathological changes in typical cases of this disease are mainly the formation of cortical papillary scars, renal calyx dilation, torsion, with the most significant lesions at the lower and upper poles of the kidney. Lesions can be unilateral or bilateral, and the diameter of the kidney can be reduced to varying degrees, or even to extreme atrophy. If a large amount of reflux continues to exist, there can be ureteral dilation and curvature.

　　The kidney atrophy caused by VUR in childhood is similar to obstructive lesions. 82% of children with kidney shrinkage of two standard deviations have moderate (IV level) to severe (V level) reflux. Scar formation is seen in 88% of children. Since the papillae at the renal poles are mainly of the complex and reflux-prone type, scars are more common, but scars can also be seen in other lobes.

　　The histopathological damage of this disease is actually not significantly different from chronic pyelonephritis, showing lymphocytic infiltration, interstitial fibrosis, tubular degenerative changes, and commonly glomerular casts in the atrophic tubules. Partial tubular cystic dilation, glomerular hyalinization or disappearance, small arteries and interlobular arteries are blocked due to contraction and intimal thickening. In some cases, pale-staining substances containing Tamm-Horsfall protein can be seen in the outer medulla and cortex, which are often surrounded by accumulated lymphocytes and plasma cells. In cases with urinary tract infection, cortical atrophy is often accompanied by severe radial inflammatory reaction, which can extend from the damaged medulla to the entire lobule. At this time, it is common to see the kidney shrink, pelvis and calyces dilate, cortex thinning, and focal scars on the kidney surface.

　　In adult cases with severe proteinuria, focal-segmental glomerulosclerosis is common, accompanied by IgM and C3 deposits. Literature reports that 50% of patients have inflammatory cell infiltration in the submucosa of the ureter and adjacent muscle layer, mainly lymphocytes and plasma cells.

　　Light microscopy examination shows tubular atrophy, interstitial fibrosis, lymphocytic infiltration, and in the cortex and outer medulla, there are staining materials containing THP in circular shapes. In advanced lesions, focal sclerosis of the glomeruli can be seen, and fluorescence microscopy shows IgM, IgG, and C3 deposits in some glomeruli. Electron microscopy examination shows electron-dense deposits under the endothelium.

　　4. Imaging examination

　　(1) Urography: The most typical change in this disease is the corresponding focal scar of the cortex with the twisted renal calices, the residual lobes can compensatory hypertrophy, presenting pseudotumor images. Generally speaking, the urography findings in patients are typical, presenting as 'standard' images, with kidney scars corresponding to twisted and club-shaped dilated renal calices, normal cortex alternating with them. When there is obstruction at the junction of the false ureter and pelvis, the kidney outline may not be special. When the lesion site is severely atrophic, the cortex covering the club-shaped renal calix becomes thin, and compensatory hypertrophy occurs in other areas, the kidney outline may also not be special.

　　(2) Ultrasound: Ultrasound examination shows irregular kidney shape, with enhanced reflection at the fibrous scar sites, normal reflection at the compensatory hypertrophy sites, and in 94% of cases, ultrasound findings are consistent with excretory urography. The sensitivity of ultrasound in detecting renal papillary morphology is not as good as intravenous pyelography, but it can detect renal scars more sensitively, while intravenous pyelography is less effective for this purpose.

　　(3) Renal Scanning: Renal scanning can be used as an auxiliary means for diagnosing reflux nephropathy. The most commonly used radionuclide is 99Tc, which has good physical properties. There are currently three different 99Tc-labeled complexes available for clinical use.

　　99Tc-labeled DTPA complex (diethylenetriamine-pentacetic acid) is filtered by the glomeruli and does not show significant retention in the renal cortex, making it particularly beneficial for evaluating the function of the collecting system and determining the total and individual glomerular filtration rates.

　　99Tc-labeled DMSA (dimercaptosuccinic acid) is slowly excreted in urine and gradually accumulates in the functional renal cortex. DMSA scans show defects that reflect low perfusion due to ischemic damage or reduced excretion of radionuclides in the proximal tubules of the damaged area.

　　99Tc-labeled glucoheptonate has the advantages of both: most of it is excreted into the renal pelvis and calyces, but a part is retained in the renal cortex. Delayed imaging for 2-3 hours after injection is particularly beneficial for detecting acute pyelonephritis and renal cortical scars, but it is not as effective as intravenous pyelography for diagnosing mild calyceal abnormalities.

　　(3) Excretory Urography (VCUG): VCUG is the traditional method for checking reflux, and it is very valuable for diagnosing urethral and bladder wall abnormalities and for precise grading of reflux. However, this examination is traumatic and painful, and it may introduce bacteria into the urethra. The application of digital subtraction in excretory urography has improved the sensitivity and accuracy of diagnosing reflux.

　　(4) Radionuclide Cystography: Radionuclide cystography developed from VCUG, with a very low radiation dose in the gonads, has become one of the available examination methods in many children's hospitals abroad. The technique is similar to VCUG, where a small amount of 99Tc is injected into the bladder after the urethral catheter is inserted, and then the bladder is filled with normal saline. Imaging of the bladder and upper abdomen is taken during bladder filling, urination, and emptying. Comparing radionuclide cystography with radioactive X-ray excretory cystography (VCUG), the former is now considered the most effective screening method for detecting reflux and judging the efficacy of surgery, with the advantage of low radiation dose; high sensitivity; and the ability to obtain data parameters such as residual volume, reflux volume, and bladder volume at the time of reflux that cannot be obtained by VCUG. The disadvantages of radionuclide cystography include the inability to evaluate the urethral condition; the inability to grade according to international grading standards; and the inability to display mild bladder wall abnormalities such as small diverticula. The indications for choosing radionuclide cystography are as follows:

　　① Follow-up examination for patients with reflux who receive medical treatment or follow-up after surgery.

　　② Screening for asymptomatic siblings of children with reflux.

　　③ Systematic examination for children prone to vesicoureteral reflux (such as myelomeningoceles or other functional bladder diseases).

　　④ Preliminary screening of female children with urinary tract infection (UTI).

　　(5) Computerized Tomography (CT): It is relatively accurate for detecting renal cortical scars, but it is quite expensive.

　　What kind of food is good for the body for chronic reflux nephropathy:

　　Eat more pork kidneys, chives, walnuts, nuts, drink more water, drink less alcohol, do appropriate exercise, and can do some lumbar massage.

　　1. Treatment

　　The glomerular filtration function of some patients with this disease can remain stable for a long time, while the renal function of other patients progresses to renal failure.

　　When the ureterovesical junction matures, 2/3 of the reflux will disappear, so for patients with reflux, the main treatment is to treat infection, prevent damage to the upper urinary tract, and at the same time, pay attention to and treat lower bladder obstruction.

　　Antihypertensive treatment is an important aspect of reflux nephropathy treatment. Studies have shown that persistent high reflux, urinary tract infection, and the presence of hypertension at the same time are factors that promote the progression of renal function damage to end-stage renal failure.

　　Proteinuria is the most important sign of renal function damage. Now it is recognized that proteinuria indicates that concurrent glomerular lesions can progress in the absence of concurrent infection and hypertension, or after correction of reflux by surgical operation.

　　Antireflux surgery does not affect the progression of glomerular lesions, focal segmental glomerulosclerosis is an important factor in the progression of the disease to renal failure. Therefore, conservative treatment should be considered first for primary ureteral reflux, and only when infection recurs after sufficient drug treatment and there are lesions in the upper urinary tract, should antireflux surgery be considered. When the diameter of the submucosal tunnel of the bladder wall ureter is normal, an 8cm-long mucosal submucosal tunnel can prevent reflux.

　　Smith studied the relationship between unilateral renal involvement, hypertension, and nephrectomy, concluding that even if the unilateral kidney is significantly involved, nephrectomy should still be cautious.

　　For lower urinary tract dysfunction caused by neurological diseases, intermittent bladder catheterization, prophylactic antibiotic treatment, and combined treatment with anticholinergic factors can successfully prevent detrusor overactivity in some cases.

　　In patients with spinal cord injury, measures to reduce the outlet resistance of the bladder, such as α-adrenergic blocking drugs and striated muscle antispasmodic therapy, or surgical application of endoscopic separation of the external urethral sphincter, or application of recently developed urethral rings or tubes to support the urethra, can reduce and eliminate reflux. Intermittent bladder catheterization can also be applied.

　　Experts such as Ye Ren believe that many VURs occurring in infants and young children can be self-resolved, but if VUR persists into adolescence, or severe VUR, it is rarely self-resolving. The current view is that internal medicine therapy is more advisable, and surgical reflux surgery should be strictly indicated and cautiously adopted.

　　1. Internal medicine treatment

　　(1) Prevention of urinary tract infection: Regularly empty the bladder, the most important is to urinate twice (the second time within 5 minutes); long-term low-dose antibacterial therapy, the most commonly used is to take half a tablet of sulfamethoxazole/trimethoprim (sulfamethoxazole/trimethoprim) before going to bed every night, for 6 months, then stop the medicine and observe. If urinary tract infection recurs, treatment should be restarted, with a course of 1 to 2 years. For those allergic to sulfonamides, methotrexate (trimethoprim) 50 to 100 mg can be taken every night. Quinolone drugs can also be used, such as ofloxacin (flumequine) 0.1g taken every night.

　　(2) Prevention and treatment of dehydration: Adequate water intake should be ensured because these patients cannot excrete concentrated urine, so they are very prone to dehydration in clinical practice; in addition, drinking more water can reduce the hyperosmotic state of the renal medulla, which is beneficial for infection control.

　　(3) Active antihypertensive treatment: Use the new step therapy for hypertension (see renal实质 hypertension).

　　(4) Traditional Chinese Medicine treatment: The basic formula we commonly use is Buyang Huanwu Decoction: 30g of Astragalus, 9g of Angelica sinensis, 10g of Peony, 6g of Chuanxiong, 9g of Earthworm, 9g of Peach Kernel, 9g of Safflower. Modify and adjust according to the symptoms. This formula can replenish Qi and activate blood, remove blood stasis and unblock collaterals, and is suitable for syndromes of Qi deficiency and blood stasis, and collaterals blocked by stasis.

　　2. Surgical treatment, its surgical indications are limited to:

　　(1) Severe reflux, especially in patients with bilateral reflux. Preoperatively, undergo 4 years of conservative medical treatment, if reflux persists or there is progressive renal function decline or new scar formation.

　　(2) Recurrent urinary tract infections, especially acute infections with fever symptoms, where VUR has not improved after 4 months of medical treatment.

　　(3) The ureteral orifice changes into a golf hole-like shape.

　　(4) Congenital anomalies or urinary tract obstruction that can be corrected by surgery.

　　There is still disagreement on whether to choose surgical treatment for adult VUR. Some suggest that adult reflux patients with asymptomatic bacteriuria or urinary tract obstruction should consider surgical treatment. In addition, many authors recently recommend the use of endoscopic injection of polytetrafluoroethylene (teflon) for VUR. Reports show that the success rate in children is 87% to 93%, and in adults it is 73%.

　　II. Prognosis

　　Recent studies have shown that the prognosis of RN is closely related to proteinuria, focal segmental glomerulosclerosis, and progressive renal function decline. The degree of proteinuria is significantly correlated with the presence and severity of glomerular injury. Progressive glomerulosclerosis is the main determinant of chronic renal failure in RN.