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Vesicoureteral Reflux and Reflux Nephropathy

By Navin Jaipaul, MD, MHS

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Reflux nephropathy is renal scarring presumably induced by vesicoureteral reflux of infected urine into the renal parenchyma. The diagnosis is suspected in children with UTI or a family history of reflux nephropathy,or if a prenatal ultrasound shows hydronephrosis. Diagnosis is by voiding cystourethrography or radionuclide cystography. Children with moderate or severe reflux are treated with prophylactic antibiotics or surgical correction.

Reflux nephropathy is a type of chronic tubulointerstitial nephritis (see also Overview of Tubulointerstitial Diseases). Traditionally, the mechanism of renal scarring has been thought to be chronic pyelonephritis. 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 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.

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 yr are unusual but may occur after acute pyelonephritis.

Symptoms and Signs

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

  • Initial screening with ultrasonography

  • Voiding cystourethrography or radionuclide cystography

Reflux nephropathy may be suspected prenatally or postnatally. Initial screening is done with ultrasonography, which is highly sensitive.

Diagnosis and staging of reflux nephropathy (prenatal or postnatal presentation) are ultimately made with voiding cystourethrography (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 VUR.

Postnatal diagnosis

VUR is suspected postnatally in patients with any of the following:

  • UTI at age 3 yr

  • Febrile UTI at age 5 yr

  • Recurrent UTIs in children

  • UTI in males

  • Strong family history, such as a sibling with VUR (controversial)

  • Adults (or children > 5 yr) with recurrent UTI in whom renal ultrasonography reveals scarring or a urinary tract anatomic abnormality

Laboratory abnormalities may include proteinuria, Na wasting, hyperkalemia, metabolic acidosis, renal insufficiency, or a combination.

Testing for these patients is with RNC or VCUG. 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

  • Usually prophylactic antibiotics

  • Surgical treatment if 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 yr.

Key Points

  • Consider reflux nephropathy in children < 5 yr 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 VCUG 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 yr.

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* This is the Professional Version. *