Reflux nephropathy

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

　　One, Primary vesicoureteral reflux

　　Primary vesicoureteral reflux is the most common in clinical practice. It is more common in children. It is a congenital abnormality of the submucosal ureteral segment of the bladder, such as congenital shortening of the submucosal ureteral segment of the bladder, underdevelopment of the trigone muscle tissue, etc. With the growth of children, the development of the bladder base is perfect, and most of the reflux will disappear.

　　Two, Secondary vesicoureteral reflux

　　Secondary vesicoureteral reflux 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), etc.

　　Three, Grading of vesicoureteral reflux

　　The widely accepted standard is still the reflux degree grading standard proposed by the International Children's Bladder Ureteral Reflux Study Group:

　　1. The Ⅰst grade only involves the ureter.

　　2. The Ⅱnd grade involves the ureter and renal pelvis, with no expansion of the renal calyces, and normal renal calyceal dome.

　　3. Mild to moderate expansion and (or) curvature of the Ⅲrd grade ureter, mild to moderate expansion of the renal pelvis, the dome is without or only slightly blunt.

　　4. Moderate expansion and (or) curvature of the Ⅳth grade ureter, moderate expansion of the renal pelvis and calyces, the acuteness of the dome disappears, but most renal papillae shapes exist.

　　5. Severe expansion and curvature of the Ⅴth grade ureter, renal pelvis, and calyces, with most renal papillae shapes disappearing.

　　The late-stage common complications of reflux nephropathy are hypertension, with an incidence rate of 10.6% to 38.1%; some cases may be asymptomatic for a long time and gradually develop into late-stage renal insufficiency and uremia.

　　The clinical manifestations of reflux nephropathy are divided into 5 types:

　　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 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 into renal reflux;

　　4. End-stage renal failure: Reflux nephropathy is one of the main causes of pediatric end-stage renal failure. Preeclampsia can be the initial symptom of reflux nephropathy, and pregnant women with reflux nephropathy can lead to rapid deterioration of renal function after pregnancy.

　　5. Other: such as polyuria, nocturia, enuresis, fever, abdominal pain, lumbar pain, urinary tract stones, hematuria, etc., primary vesicoureteral reflux has a familial tendency.

　　This disease is caused by multiple etiologies, and 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.

　　Classification and methods of clinical examination methods for reflux nephropathy

　　First, laboratory examinations

　　1. Urinalysis. In cases of urinary tract infection, sediment examination shows leukocyte urine or pyuria, and urine bacterial culture is positive. White blood cells, red blood cell casts, tubular proteinuria, microscopic hematuria, and significant decreases in urine specific gravity and urine osmolality are observed, indicating renal damage. Urinary NAG enzyme and urinary β2-MG levels are elevated. Decreased concentrating function and reduced reabsorption of β2-microglobulin suggest tubular dysfunction. Proteinuria exceeding 1 gram per day suggests secondary focal segmental glomerulosclerosis.

　　2. Blood tests. Blood leukocyte count elevation, left shift, and other systemic infectious symptoms can be seen, and Tamm-Hosfall antibody is positive, IgG level is elevated. Nephrotic syndrome and elevated blood creatinine levels may occur when acute renal failure occurs. Hypernatremia may occur when the concentrating ability decreases.

　　Second, other auxiliary examinations

　　1. Renal biopsy. The pathological changes in typical cases of this disease are mainly the formation of cortical papillary scars, dilatation and torsion of the renal pelvis, and the lesions are most prominent at the lower pole and upper pole of the kidney. The lesions can be unilateral or bilateral, and the kidneys can shrink to varying degrees or even become extremely atrophic. If a large amount of reflux continues to exist, there may be dilatation and curvature of the ureter.

　　2. Histological examination. The histological damage of reflux nephropathy is actually indistinguishable from chronic pyelonephritis, showing lymphocytic infiltration, interstitial fibrosis, tubular degenerative changes, and glomerular hyaline change or disappearance. Small arteries and interlobular arteries are blocked due to contraction and intimal thickening. In some cases, faintly stained substances containing Tamm-Horsfall protein are visible in the outer medulla and cortex. These lesions are often surrounded by accumulated lymphocytes and plasma cells. In cases with urinary tract infection, cortical atrophy is often accompanied by severe radiating inflammatory reactions, which can extend from the damaged medulla to the entire lobe, at which time the kidney often shrinks, the renal pelvis and calyces dilate, the cortex becomes thin, and focal scars appear on the renal surface.

　　3. Light microscopy and electron microscopy examination. Light microscopy examination shows renal tubular atrophy, interstitial fibrosis, lymphocytic infiltration, and the presence of THP-containing round stains in the cortex and outer medulla. In advanced lesions, there is focal glomerulosclerosis, and fluorescence microscopy reveals IgM, IgG, and C3 deposits in some glomeruli. Electron microscopy examination shows subendothelial electron-dense deposits.

　　3. Imaging Examination

　　1. Urography. The most typical change in this disease is the focal scar in the cortex corresponding to the twisted calyces. The residual lobes can compensate for hypertrophy and present as pseudo-tumor images. Generally speaking, the patient's urography is typical, showing the 'standard' image. The renal scars correspond to twisted and club-shaped dilated calyces, alternating with normal cortex.

　　2. Ultrasound Examination. It shows irregular renal contours, with fibrous scar sites showing increased reflection, and compensatory hypertrophy sites showing normal reflection. The results of ultrasound examination are consistent with those of excretory urography in 94% of cases. The sensitivity of ultrasound examination in detecting renal papillary morphology is not as good as that of intravenous pyelography, but it can detect renal scars sensitively. Intravenous pyelography is not effective for this.

　　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. ① The 99Tc-labeled DTPA complex is filtered by the glomerulus and shows no significant retention in the renal cortex, making it particularly advantageous for evaluating the function of the collecting system and determining the total and individual glomerular filtration rates. ② The 99Tc-labeled DMSA is excreted slowly with urine and gradually accumulates in the functional renal cortex, and the DMSA scan defect reflects the hypoperfusion or reduced excretion of radionuclide at the site of ischemic damage or near the proximal tubule. ③ The 99Tc-labeled glucuronate has the advantages of both: most is excreted into the renal pelvis and calyces, but a part is retained in the renal cortex. The delayed imaging of 2-3 hours after injection is particularly advantageous for detecting acute pyelonephritis and renal cortex scars, but is not as effective for diagnosing mild calyceal abnormalities as intravenous pyelography.

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

　　5. Radionuclide Cystography. Radionuclide cystography has developed from VCUG and has a very low radiation dose in the gonads, becoming one of the available examination methods in many children's hospitals abroad. Compared with radionuclide cystography and radioisotope X-ray excretory urography (VCUG), the former is now considered the most effective method for screening reflux and judging the effectiveness 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 from VCUG. The disadvantages of radionuclide cystography include the inability to evaluate the urethral condition; the inability to be graded according to international grading standards; and the inability to display mild bladder wall abnormalities such as small diverticula. The indications for radionuclide cystography are as follows: ① Follow-up examination after medical treatment or surgery in patients with reflux. ② Screening of asymptomatic siblings of children with reflux. ③ Systematic examination of children prone to vesicoureteral reflux (such as myelomeningocele or other functional bladder diseases). ④ Preliminary screening of female children with UTI.

　　6. Computerized tomography (CT). It is relatively accurate for detecting renal cortical scars, but the price is relatively expensive.

　　Patients should eat more pork kidneys, chives, walnuts, and other nuts; drink more water, drink less alcohol, do appropriate exercise, and can do some lumbar massage. In addition, patients should also pay attention to avoiding spicy, greasy, and cold foods.

　　The principles of Western medicine treatment and medication for reflux nephropathy:

　　First, the principle of treatment

　　1. Stop urine reflux.

　　2. Control urinary tract infection and hypertension.

　　3. Surgical correction of vesicoureteral reflux.

　　4. Delay the onset of uremia.

　　5. Hemodialysis.

　　6. Renal Transplantation.

　　Second, the principle of medication

　　1. When the patient has an acute infection, it can be treated as an acute urethritis infection, such as fluoroquinolones, oxacillin, ampicillin, etc., choose one. If the effect is still not ideal, you can choose antibiotics from new special drugs. Antihypertensive drugs should be used first, and then C item if ineffective.

　　2. If the treatment effect of internal medicine is poor, consider surgical operation to correct vesicoureteral reflux. The indications are: (1) Recurrent infection that is not easily controlled by antibiotics. (2) Severe vesicoureteral reflux on one side. (3) Correctable congenital abnormalities or obstructions. (4) Partial or unilateral nephrectomy may sometimes control reflux nephropathy and hypertension.