Primary Vesicoureteral Reflux

Primary vesicoureteral reflux is retrograde passage of urine from the bladder into the ureter caused by an intrinsic defect of the ureterovesical junction (short submucosal tunnel, lateral ureteric orifice, or abnormal ureteric muscle), with a normal bladder and urethra.

• It is the commonest congenital urinary tract abnormality; about 1 percent of newborns, 30 to 40 percent of children after first febrile urinary infection, and 25 to 40 percent of siblings and offspring of affected individuals (autosomal dominant with incomplete penetrance).
• Reflux is detected less often in children of African descent; girls present with infections and boys more often with antenatal hydronephrosis and higher grades.
• Natural history: spontaneous resolution in grade I to II (80 percent in 5 years), grade III (50 to 60 percent), grade IV to V (about 25 to 30 percent), and higher grade resolves more slowly; resolution is likelier with younger age, unilateral disease and lower grade.

Febrile urinary tract infection (often the first sign), antenatal hydronephrosis found on screening, family history.

• Older children: enuresis, recurrent cystitis, hypertension, flank pain at voiding.
• Differential diagnosis: secondary reflux (posterior urethral valves, neurogenic bladder, dysfunctional voiding), obstructive uropathy, multicystic dysplastic kidney, duplex system, urolithiasis, functional bladder disorders.
• Complications: renal scarring (reflux nephropathy), recurrent pyelonephritis, hypertension, proteinuria with focal segmental glomerulosclerosis, chronic kidney disease, end stage kidney disease, pregnancy complications in women with scarring.

Urine culture; creatinine, blood pressure.

• Renal and bladder ultrasound; voiding cystourethrogram grades the reflux (I to V) and shows a normal bladder and urethra, confirming primary reflux; contrast-enhanced voiding urosonography is an alternative without radiation.
• Dimercaptosuccinic acid scan at 4 to 6 months to quantify scarring and differential function.
• Screening of siblings (renal ultrasound, then cystogram if abnormal) and of children of affected adults.
• Assess for bladder and bowel dysfunction before attributing symptoms to reflux.

Supportive: treat constipation and dysfunctional voiding, timed voiding every 2 to 3 hours, adequate fluid intake, good perineal hygiene, toilet training; treat infections promptly and reassure families about the high rate of spontaneous resolution.

Pharmacological

• Continuous antibiotic prophylaxis at night in infants under 12 months with grade III to V reflux and in children with recurrent infections: trimethoprim 2 mg/kg (or cotrimoxazole with trimethoprim 2 mg/kg), nitrofurantoin 1 to 2 mg/kg (age above 3 months), or cefalexin 10 mg/kg (infants under 2 months) or amoxicillin 10 mg/kg (under 6 weeks); stop when toilet trained with no breakthrough infections and reflux resolved or low grade.
• Treat acute infection: oral cefixime 8 mg/kg daily for 7 to 10 days, or ceftriaxone 50 to 75 mg/kg IV daily for 2 to 4 days in febrile infants then oral to complete 7 to 10 days.
• Hypertension with scarring: enalapril 0.1 to 0.5 mg/kg/day in 1 to 2 doses, monitor creatinine and potassium; amlodipine 0.1 to 0.2 mg/kg daily.

Procedures

• Endoscopic injection of dextranomer-hyaluronic acid at the ureteric orifice for grade II to IV (success about 75 percent, second injection raises to 85 to 90 percent) in children with breakthrough infections or parental choice.
• Ureteric reimplantation (Cohen or Lich-Gregoir) for grade IV to V, failure of endoscopic therapy, breakthrough infections, new scars, or associated anomalies (periureteric diverticulum, duplex ureter); minimally invasive and robotic approaches are used in some centres.
• Nephrectomy or heminephrectomy for non-functioning kidney with recurrent infection or hypertension.

Special groups: infants (prophylaxis and watchful waiting), girls with bladder dysfunction (behavioural therapy before surgery), pregnancy in women with scars (monthly cultures, prophylaxis, blood pressure monitoring, ultrasound), adolescents (stop prophylaxis when stable).

Red flags: febrile breakthrough infections, new scars on repeat scan, hypertension, falling renal function, bilateral high grade reflux, proteinuria.

Follow-up: yearly ultrasound, blood pressure, growth and urinalysis; repeat cystography only if decisions depend on it; adult follow-up for scarred patients with blood pressure, urine albumin and creatinine yearly.