Vesicoureteral Reflux

Vesicoureteral reflux is retrograde flow of urine from the bladder into the ureter and sometimes the renal pelvis.

• Primary reflux is due to a congenitally short or abnormally placed intramural ureter; secondary reflux is due to raised bladder pressure or abnormal bladder function (posterior urethral valves, neurogenic bladder, bladder and bowel dysfunction, ureterocele, duplex system, urethral obstruction, catheterisation, after surgery).
• It affects 1 to 2 percent of children and 30 to 40 percent of children with febrile urinary tract infection; there is a strong familial tendency (30 to 50 percent of siblings).
• Severity is graded I to V by radiological appearance: I ureter only, II ureter and pelvis without dilatation, III mild to moderate dilatation, IV moderate dilatation with blunted fornices, V gross dilatation and tortuous ureter with loss of papillary impressions.

Febrile urinary tract infection (the commonest presentation in infants and children), failure to thrive, antenatal hydronephrosis, family history, bladder and bowel dysfunction (urgency, wetting, constipation).

• Older children and adults: hypertension, proteinuria, loin pain on voiding, renal impairment, pregnancy complications (pyelonephritis, pre-eclampsia).
• Differential diagnosis: obstructive uropathy (pelviureteric junction obstruction, megaureter), multicystic dysplastic kidney, posterior urethral valves, duplex kidney, bladder dysfunction without reflux, urolithiasis.
• Complications: renal scarring (reflux nephropathy), recurrent pyelonephritis, hypertension (10 to 20 percent of scarred), proteinuria, chronic kidney disease and end stage kidney disease (5 to 10 percent of paediatric end stage disease), pregnancy complications.

Urinalysis and culture; creatinine and blood pressure.

• Renal and bladder ultrasound after the first febrile urinary infection and in antenatal hydronephrosis.
• Voiding cystourethrogram (fluoroscopic) for grading, after the infection has resolved, in infants with abnormal ultrasound, recurrent infection, or atypical infection; or contrast-enhanced voiding urosonography.
• Dimercaptosuccinic acid scan 4 to 6 months after infection to detect scarring; diuretic renography if obstruction suspected; urodynamics if bladder dysfunction.
• Siblings: ultrasound first and cystogram if abnormal or infected.

Supportive: adequate fluid intake, timed voiding every 2 to 3 hours, treat constipation (macrogol 0.4 to 0.8 g/kg daily), perineal hygiene, bladder and bowel retraining; circumcision in infant boys with high grade reflux reduces infection.

Pharmacological

• Treatment of breakthrough infection: oral cefixime 8 mg/kg daily or amoxicillin-clavulanate 25 mg/kg/day (amoxicillin component) in two doses for 7 to 10 days; parenteral ceftriaxone 50 to 75 mg/kg daily in febrile infants or toxic children, gentamicin 5 to 7.5 mg/kg daily; adjust the choice to culture results.
• Continuous antibiotic prophylaxis (in infants and children with high grade reflux, recurrent infection, or scarring): trimethoprim 2 mg/kg at night (or cotrimoxazole with 2 mg/kg trimethoprim), nitrofurantoin 1 to 2 mg/kg at night (avoid in infants under 3 months), cefalexin 10 mg/kg at night (infants under 2 months), or amoxicillin 10 mg/kg at night for neonates under 6 weeks; continue until toilet trained and reflux resolves.
• Hypertension: ACE inhibitor (enalapril 0.1 to 0.5 mg/kg/day), caution with bilateral scarring.
• Anticholinergic (oxybutynin 0.2 mg/kg two to three times daily) for overactive bladder in older children.

Procedures

• Endoscopic subureteric injection of a bulking agent (dextranomer-hyaluronic acid, 0.5 to 1.5 mL) for grades II to IV (success 70 to 85 percent), as day case surgery.
• Open or laparoscopic ureteric reimplantation (Cohen cross-trigonal or Lich-Gregoir techniques; success above 95 percent) for high grade (IV to V), breakthrough infections, new scars, anatomical abnormalities, or failed endoscopic therapy.
• Posterior urethral valve ablation for secondary reflux; nephrectomy for non-functioning scarred refluxing kidney with hypertension.

Special groups: neonates and infants (prophylaxis and surveillance), pregnant women with reflux nephropathy (monthly urine culture, antibiotic prophylaxis, blood pressure monitoring), adults (antibiotic prophylaxis if recurrent infections).

Red flags: breakthrough febrile infection, new scars, hypertension, falling eGFR, gross hydronephrosis, bladder outlet obstruction.

Follow-up: annual ultrasound, blood pressure, height, weight and urinalysis; repeat voiding cystourethrogram or nuclear cystogram at 12 to 24 months if surveillance; consider stopping prophylaxis when toilet trained and no infections; long term follow-up of scarring into adulthood.