(See also Overview of Tubulointerstitial Diseases Overview of Tubulointerstitial Diseases Tubulointerstitial diseases are clinically heterogeneous disorders that share similar features of tubular and interstitial injury. In severe and prolonged cases, the entire kidney may become... read more and Vesicoureteral Reflux Vesicoureteral Reflux (VUR) Vesicoureteral reflux is retrograde passage of urine from the bladder back into the ureter and sometimes also into the renal collecting system, depending on severity. Reflux predisposes to urinary... read more in the chapter on Congenital Renal and Genitourinary Anomalies.)
Reflux nephropathy involves a type of chronic tubulointerstitial nephritis as well as glomerular-mediated injury. Traditionally, the mechanism of renal scarring has been thought to be chronic pyelonephritis Chronic Pyelonephritis Chronic pyelonephritis is continuing pyogenic infection of the kidney that occurs almost exclusively in patients with major anatomic abnormalities. Symptoms may be absent or may include fever... read more . However, reflux is probably the single most important factor, and factors unrelated to reflux or pyelonephritis (eg, congenital factors) can contribute.
Vesicoureteral reflux (VUR) affects about 1% of neonates and 30 to 45% of young children with a febrile urinary tract infection Urinary Tract Infection (UTI) in Children Urinary tract infection (UTI) is defined by ≥ 5 × 104 colonies/mL in a catheterized urine specimen or, in older children, by repeated voided specimens with ≥ 105 colonies/mL... read more (UTI); it is common among children with renal scars and, for unknown reasons, is less common among Black children than White children. Familial predisposition is common. Children with gross reflux (up to the renal pelvis plus ureteral dilation) are at highest risk of scarring and subsequent chronic kidney disease Chronic Kidney Disease Chronic kidney disease (CKD) is long-standing, progressive deterioration of renal function. Symptoms develop slowly and in advanced stages include anorexia, nausea, vomiting, stomatitis, dysgeusia... read more 
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Reflux requires incompetent ureterovesical valves or mechanical obstruction in the lower urinary tract. Young children with shorter intravesical portions of the ureter are most susceptible; normal growth usually results in spontaneous cessation of intrarenal and vesicoureteral reflux by age 5. New scars in children > 5 years are unusual but may occur after acute pyelonephritis.
Symptoms and Signs of VUR and Reflux Nephropathy
Few symptoms and signs other than occasional UTI are present in young children, and the diagnosis is often overlooked until adolescence, when patients present with some combination of the following:
Polyuria
Nocturia
Hypertension
Symptoms and signs of renal insufficiency
Diagnosis of VUR and Reflux Nephropathy
Initial screening with ultrasonography
Voiding cystourethrography or radionuclide cystography
Reflux nephropathy may be suspected prenatally or postnatally. Initial screening is done with ultrasonography.
Diagnosis and staging of reflux nephropathy (prenatal or postnatal presentation) are ultimately made with voiding cystourethrography Cystourethrography Imaging tests are often used to evaluate patients with renal and urologic disorders. Abdominal x-rays without radiopaque contrast agents may be done to check for positioning of ureteral stents... read more (VCUG), which can demonstrate the degree of ureteral dilation. Radionuclide cystography (RNC) can also be used; it provides less anatomic detail than VCUG but involves less radiation exposure. Renal scarring is diagnosed with technetium-99m–labeled dimercaptosuccinic acid (DMSA) radionuclide scanning.
Prenatal diagnosis
The diagnosis is suspected prenatally if ultrasonography, done because of a family history or for unrelated reasons, shows hydronephrosis; 10 to 40% of such patients are diagnosed postnatally with vesicoureteral reflux (VUR).
Postnatal diagnosis
Vesicoureteral reflux is suspected postnatally in patients with any of the following:
UTI at age ≤ 3 years
Febrile UTI at age ≤ 5 years
Recurrent UTIs in children
UTI in males
Strong family history, such as a sibling with VUR (controversial)
Adults (or children > 5 years) with recurrent UTI in whom renal ultrasonography reveals scarring or a urinary tract anatomic abnormality
Laboratory abnormalities may include proteinuria, sodium wasting, hyperkalemia, metabolic acidosis, renal insufficiency, or a combination.
Testing for these patients is with radionuclide cystography or voiding cystourethrography. Because these tests involve catheterization (and risk of UTI) as well as radiation exposure, thresholds for obtaining them can be controversial. Some experts recommend VCUG or RNC only if family history is strong or if postnatal renal ultrasonography is markedly or persistently abnormal; however, it is not clear whether renal ultrasonography is sufficiently sensitive to detect VUR. DMSA scanning may be done for infants or children with UTIs as listed above.
In older children in whom reflux is no longer active, VCUG may not show reflux, although DMSA scanning shows scarring; cystoscopy can demonstrate evidence of previous reflux at ureteral orifices. Thus, DMSA scanning and cystoscopy may be done if prior reflux is suspected but not confirmed.
Renal biopsy at this late stage shows chronic tubulointerstitial nephritis and focal glomerulosclerosis, which may cause mild (1 to 1.5 g/day) to nephrotic-range (3.5 g/day) proteinuria.
Treatment of VUR and Reflux Nephropathy
Usually prophylactic antibiotics
Surgical treatment if vesicoureteral reflux (VUR) is moderate or severe
Treatment of reflux nephropathy is based on the unproven assumption that decreasing reflux and UTIs prevents renal scarring. Children with very mild VUR require no treatment, but they should be closely observed for symptoms of UTI.
Children with moderate reflux are usually given antibiotics. However, drug therapy predisposes to new episodes of acute pyelonephritis, and it is not clear whether prophylactic antibiotics are more effective than close observation.
Patients with severe reflux are at higher risk of renal insufficiency and are usually given antibiotic prophylaxis or undergo surgical interventions, including ureteral reimplantation or endoscopic injection of materials behind the ureter to prevent reflux (bladder contraction during voiding compresses the ureter between the bladder and the material). Incidence of new renal scars is similar in patients treated with surgery and with drugs.
Reflux spontaneously resolves in about 80% of young children within 5 years.
Key Points
Consider reflux nephropathy in children < 5 years with UTIs or a family history, particularly among boys or if patients have fever or recurrent UTIs.
If reflux nephropathy is suspected, do ultrasonography; if abnormal, consider voiding cystourethrography or, to minimize radiation exposure, radionuclide cystography.
Consider prophylactic antibiotics and, if reflux is severe, surgical treatment.
Consensus is lacking for certain recommendations, such as when and how to image patients for diagnosis and when to prescribe prophylactic antibiotics.
Reflux spontaneously resolves in about 80% of young children within 5 years.
