Reflux nephropathy

Reflux nephropathy is a form of chronic tubulointerstitial kidney disease caused by renal scarring associated with vesicoureteric reflux (VUR), particularly when reflux occurs during infancy and early childhood. It develops as a result of the retrograde flow of urine from the bladder into the ureters and kidneys, leading to recurrent urinary tract infections and progressive renal parenchymal damage. Reflux nephropathy may occur in association with congenital abnormalities of the urinary tract, including renal dysplasia, duplex collecting systems, and posterior urethral valves. It is an important cause of chronic kidney disease, hypertension, and end-stage kidney disease in children and young adults.

Epidemiology

Reflux nephropathy commonly originates during childhood and is one of the leading causes of chronic kidney disease in children and young adults. It is more frequently identified in individuals with a history of recurrent urinary tract infections, vesicoureteric reflux, or congenital anomalies of the urinary tract. Early diagnosis and management of vesicoureteric reflux have reduced the incidence of severe renal scarring in many settings.

Risk factors

• Vesicoureteric reflux (VUR)

• Recurrent urinary tract infections, particularly pyelonephritis

• Congenital renal dysplasia

• Posterior urethral valves

• Obstructive uropathy

• Duplex collecting system and other urinary tract anomalies

• Delayed diagnosis or treatment of urinary tract infections

• Family history of vesicoureteric reflux

• Neurogenic bladder

• Bladder dysfunction causing urinary stasis

Pathophysiology

Vesicoureteric reflux allows urine to flow backward from the bladder into the ureters and renal collecting system. This retrograde flow facilitates the ascent of bacteria into the kidneys, resulting in recurrent episodes of pyelonephritis. Repeated infection and inflammation lead to renal cortical scarring and progressive destruction of renal tissue.

Some patients have congenital renal dysplasia in addition to reflux, resulting in abnormal renal development and reduced nephron number. Progressive scarring causes loss of functional renal tissue, activation of the renin-angiotensin-aldosterone system, and subsequent hypertension. Over time, persistent nephron loss may lead to proteinuria, chronic kidney disease, and eventually end-stage kidney disease.

Clinical presentation

Reflux nephropathy may remain undetected for many years and is often discovered during evaluation for hypertension, recurrent urinary tract infections, or impaired kidney function.

Symptoms

• Usually asymptomatic

• Frequency of micturition

• Dysuria

• Aching lumbar or flank pain

• Symptoms of recurrent urinary tract infections

• Nocturia

• Polyuria in advanced disease

• Symptoms related to chronic kidney disease in late stages

Clinical signs

• Hypertension

• Costovertebral angle tenderness during active infection

• Growth retardation in children with chronic kidney disease

• Signs of chronic kidney disease in advanced cases

• Evidence of congenital urinary tract abnormalities

• Peripheral oedema in advanced renal impairment

Diagnostic criteria

The diagnosis of reflux nephropathy is based on:

• Evidence of renal cortical scarring on imaging studies

• Presence or previous history of vesicoureteric reflux

• History of recurrent urinary tract infections, especially pyelonephritis

• Evidence of renal dysfunction, hypertension, or proteinuria

• Exclusion of other causes of chronic kidney disease and renal scarring

Investigations

Laboratory investigations

• Urinalysis (dipstick, biochemistry, and microscopy)

• Urine culture and sensitivity

• Serum creatinine

• Estimated glomerular filtration rate (eGFR)

• Serum electrolytes

• Urine protein assessment

• Full blood count where indicated

Imaging investigations

• Ultrasonography of the kidneys, ureters, and bladder (KUB)

• Micturating cystourethrography (MCUG) to demonstrate vesicoureteric reflux

• Radionuclide dimercaptosuccinic acid (DMSA) renal scan to identify cortical scarring

• Serial magnetic resonance imaging (MRI) when detailed assessment is required

• Nuclear renal function studies where indicated

Histological investigation

• Renal biopsy in selected cases when diagnosis is uncertain or alternative renal pathology is suspected

Management

Management aims to prevent further renal damage, control hypertension, treat urinary tract infections, preserve renal function, and correct underlying urinary tract abnormalities.

Non-pharmacological treatment

• Regular monitoring of renal function and blood pressure

• Adequate hydration

• Prompt evaluation of symptoms suggestive of urinary tract infection

• Education regarding prevention and early recognition of urinary tract infections

• Nephrectomy may be considered when recurrent pyelonephritis occurs in a severely damaged kidney with minimal or absent function

• Removal of a severely diseased kidney may improve or cure hypertension in selected patients

• Surgical correction of severe vesicoureteric reflux through ureteric reimplantation

• Endoscopic correction using subtrigonal injection of bulking agents such as polysaccharide-based materials where appropriate

• Management of bladder dysfunction and urinary obstruction when present

Pharmacological treatment

Treatment of urinary tract infection

Urinary tract infections should be treated promptly according to local urinary tract infection treatment guidelines and culture sensitivity results.

Control of hypertension

• Enalapril 5–20 mg orally once daily, adjusted according to blood pressure and renal function

• Lisinopril 5–40 mg orally once daily, adjusted according to clinical response

Alternative antihypertensive agents may be used according to individual patient characteristics and treatment guidelines.

Management of chronic kidney disease

Patients with chronic kidney disease should receive appropriate management, including:

• Blood pressure control

• Management of proteinuria

• Correction of electrolyte abnormalities

• Nutritional support

• Renal replacement therapy when indicated

Management according to underlying cause

Vesicoureteric reflux

• Conservative monitoring for low-grade reflux

• Surgical correction for severe or persistent reflux associated with recurrent infections or progressive renal damage

Posterior urethral valves

• Definitive surgical correction of obstruction

• Long-term monitoring of renal function

Recurrent urinary tract infection

• Prompt antibiotic treatment guided by urine culture

• Investigation for underlying urinary tract abnormalities

Renal dysplasia

• Supportive management with monitoring of renal function and blood pressure

• Treatment of complications of chronic kidney disease

Referral

Refer the patient to a nephrologist or urologist if:

• Vesicoureteric reflux is confirmed

• Recurrent urinary tract infections occur despite treatment

• Hypertension is difficult to control

• Progressive renal impairment develops

• Significant proteinuria is present

• Surgical intervention is required

• Congenital urinary tract abnormalities are identified

• End-stage kidney disease is suspected

Complications

• Progressive renal scarring

• Chronic kidney disease

• End-stage kidney disease

• Persistent or severe hypertension

• Proteinuria

• Recurrent pyelonephritis

• Growth impairment in children

• Pregnancy-related complications in affected women

• Cardiovascular complications secondary to chronic kidney disease

Prognosis

The prognosis depends on the severity of renal scarring, the presence of congenital renal abnormalities, the degree of vesicoureteric reflux, and the effectiveness of infection control. Patients with mild disease may maintain stable renal function for many years, while those with extensive bilateral scarring are at increased risk of chronic kidney disease and end-stage kidney disease.

Prevention

• Early diagnosis and treatment of urinary tract infections

• Prompt investigation of recurrent febrile urinary tract infections in children

• Early detection and management of vesicoureteric reflux

• Screening of at-risk children with congenital urinary tract abnormalities

• Regular follow-up of patients with known vesicoureteric reflux

• Control of hypertension

• Prevention of recurrent pyelonephritis through appropriate medical and surgical management

• Patient and caregiver education regarding urinary tract infection prevention and early healthcare seeking behavior.