Congenital anomalies of the kidneys and urinary tract

Congenital anomalies of the kidneys and urinary tract (CAKUT) are among the most common malformations diagnosed prenatally and the leading cause of end-stage kidney disease in children. The pathogenesis of CAKUT is multifactorial; genetic mutations, clinical syndromes, and environmental factors (e.g., in utero exposure to ACE inhibitors) have been implicated in its development. CAKUT is often identified prenatally and confirmed after birth before symptoms develop, though some cases are diagnosed postnatally after symptoms or signs develop. Although many cases are initially asymptomatic, up to 50% of children with end-stage kidney disease have an underlying CAKUT. For this reason, early identification and specialist management (e.g., nephrology and/or urology) are essential to prevent kidney damage.

A disturbance in embryonic development due to: ^[1]

• Genetic mutations (hereditary or sporadic)
• Clinical syndromes, e.g.,
  • Prune belly syndrome
  • VACTERL
• Environmental factors (e.g., in utero exposure to ACE inhibitors or angiotensin II receptor blockers)

CAKUT conditions are often classified by the affected anatomic level of the urinary tract and include the following.

Kidney anomalies ^[2][3]

Abnormalities in kidney development, size, number, position, or fusion, e.g.:

• Renal dysgenesis: renal hypoplasia, renal dysplasia, renal aplasia, renal agenesis
• Congenital solitary kidney
• Horseshoe kidney
• Ectopic kidney, including crossed renal ectopia
• Renal malrotation

Urinary tract anomalies ^[2][3][4][5]

Abnormalities of the renal collecting system, ureters, bladder, or urethra, e.g.:

• Duplex collecting system
• Ectopic ureter
• Primary megaureter
• Ureterocele
• Ureteral stenosis
• Ureteropelvic junction obstruction
• Vesicoureteral reflux (VUR)
• Bladder abnormalities
• Posterior urethral valves

Renal dysgenesis

• Renal hypoplasia: underdevelopment of the kidney characterized by a reduced number of nephrons
• Renal dysplasia: abnormal development of the kidney that results in a nonfunctional kidney with abnormal features (e.g., cysts, increased amount of connective tissue)
  • Pathophysiology: Ureteric bud does not properly stimulate differentiation of metanephric blastema → disorganized nephrons, reduced number of nephrons, and abnormal cells
  • Unilateral dysplasia is usually asymptomatic.
  • Bilateral dysplasia leads to early renal insufficiency and Potter sequence if present in utero
  • Examples: multicystic dysplastic kidneys, obstructive cystic dysplasia
  • Associated with anomalies of the collecting system that predispose to UTI
• Renal aplasia: kidney with only rudimentary renal parenchyma present with no residual function
• Renal agenesis: the absence of the kidney and the ureter
  • ♂ > ♀
  • Pathophysiology: ureteric bud does not develop → complete lack of stimulating signals for differentiation of metanephric blastema → kidney fails to develop.
  • Unilateral renal agenesis: usually asymptomatic, depending on the condition of the other kidney
  • Bilateral renal agenesis: causes Potter sequence

Congenital solitary kidney

• The presence of a single functioning kidney due to the absence or anomalies of the contralateral kidney
  • Anatomical congenital solitary kidney: the absence of one kidney due to renal agenesis
  • Functional congenital solitary kidney: a nonfunctional kidney due to e.g., renal aplasia, severe renal dysplasia or hypoplasia
• Often asymptomatic and diagnosed during prenatal ultrasound screening
• A solitary kidney is usually hypertrophic to compensate for the contralateral kidney
• Higher incidence of anomalies (e.g., VUR)
• Increased risk of hypertension, renal insufficiency, and progression to end-stage kidney disease

• Horseshoe kidney: Fusion of the left and right inferior renal poles
  • Normal ascent interrupted as fused kidney gets caught on the inferior mesenteric artery (IMA).
  • Increased incidence in patients with chromosomal aneuploidy (e.g., trisomies 13, 18, 21, and Turner syndrome)
  • Usually asymptomatic; typically diagnosed incidentally on abdominal imaging for unrelated conditions
  • Rarely requires treatment
  • Increased risk of renal stones, ureteropelvic junction obstruction, hydronephrosis, infections, and renal cancer
• Renal ectopia: displacement of the kidney within the retroperitoneum
• Crossed renal ectopia: displacement of the kidneys; both kidneys located on the same side of the spine
• Malrotation: torsion of the orthotopic kidney

• Duplex collecting system: a complete or incomplete duplication of the collecting system (pelvicalyceal system and ureter); has different clinical manifestations depending on the degree of fusion
  • The most common congenital anomaly of the urinary tract
  • Complete duplication: an additional ureteric bud forms resulting in two separate ureteric buds that interact with the same metanephric blastema; the affected kidney has ; two separate pelvicalyceal systems and two ureters that enter the bladder at different points (double ureter).
  • Incomplete duplication: the ureteric bud splits before interacting with the metanephric blastema; the affected kidney has two collecting systems that merge between the ureteropelvic junction and the urinary bladder, resulting in a single ostium in the bladder
    • Bifid ureter; : The affected kidney has two separate pelvicalyceal systems and two ureters that merge and share a single ostium into the bladder (Y-shaped ureter).
    • Bifid pelvis: The affected kidney has two separate pelvicalyceal systems that merge into a single ureter at the ureteropelvic junction.
  • Associated with VUR, ureteral stricture, hydronephrosis, and UTI
  • Ureteroureteral reflux may occur due to Y-shaped ureter.
• Megaureter: See "Megaureter" for detailed information.
• Ectopic ureter: The ureter opening is located caudal to the normal insertion site on the bladder.
  • Prenatal hydronephrosis
  • Postnatal UTI
  • In female individuals, the ureter may bypass the external sphincter and insert directly in the vagina, resulting in incontinence.
• Ureterocele: abnormal dilation of the terminal portion of the ureter, which bulges into the urinary bladder or extends to the bladder neck and the urethra; often appears balloon-shaped on cystoscopy
  • Prenatal hydronephrosis
  • Postnatal UTI
• Ureteral obstruction (e.g., ureteral stenosis, ureteropelvic junction obstruction): See “Urinary tract obstruction” for detailed information.
• Vesicoureteral reflux: See "Vesicoureteral reflux" for detailed information.

Posterior urethral valves

• Definition: congenital malformation in males where membranous folds of the urogenital membrane obstruct the membranous and prostatic urethra (posterior urethra)
• Epidemiology: incidence is about 1 per 4,000 live births ^[6]
• Clinical features ^[7]
  • Most common cause of urinary tract obstruction in newborn males
  • Respiratory distress secondary to pulmonary hypoplasia in cases with severe obstruction (see “Potter sequence”)
  • Abdominal distention due to bladder distention
  • Late manifestations:
    • Difficulty voiding, poor urinary stream
    • UTIs → urosepsis
    • Diurnal enuresis
    • Failure to thrive
• Diagnostics
  • Voiding cystourethrogram (diagnostic study of choice) demonstrates
    • Dilation/elongation of the posterior urethra during voiding
    • Signs of VUR (if present)
  • Prenatal ultrasound of the upper urinary tract may demonstrate:
    • Distended and/or thick-walled bladder
    • Bilateral hydroureters
    • Bilateral hydronephrosis
    • Marked VUR with megaureter
    • Oligohydramnios and features of Potter sequence (in severe urinary outflow obstruction)
• Treatment
  • Temporary insertion of urinary catheter and correction of electrolyte imbalance
  • First-line: primary valve ablation
    • An endoscopic procedure that involves the transurethral incision of posterior urethral valves in the membranous part of the urethra
    • Performed during cystoscopy
  • Second-line: vesicostomy
    • A surgical procedure in which a connection is formed between the bladder and the outside of the lower abdominal wall to allow for the drainage of urine (or if ablation is not possible)
    • Also indicated in patients with functional bladder outlet obstruction (e.g., neurogenic bladder)
  • Close follow-up due to high risk of chronic kidney disease
  • Renal transplantation may become necessary during the course of disease.
  • Fetal vesicoamniotic shunting is associated with procedure-related risks without evidence of long-term benefits for renal function
• Complications: most common cause of chronic renal insufficiency or renal failure in boys

Many patients with CAKUT are asymptomatic. In symptomatic patients, the clinical presentation varies based on the type and severity of the condition and can include any of the following: ^[2][3][4]

• Recurrent urinary tract infections (UTIs)
• Clinical features of VUR
• Hypertension
• Proteinuria
• Signs or complications of chronic kidney disease (CKD), e.g., growth faltering ^{[8] [2]}
• Features of associated genetic syndromes ^[4]

Severe forms of CAKUT can cause fetal demise, while patients with less severe forms may be asymptomatic or develop symptoms in adulthood. ^[3]

• CAKUT can be diagnosed in utero or as late as adulthood in affected patients. ^[3]
• Milder forms of CAKUT may go undetected until later in life, with the onset of chronic kidney disease. ^[3]

Indications ^[4][5]

Additional prenatal evaluation is indicated when any of the following are detected on routine second-trimester ultrasound: ^[9][10][11]

• Prenatal urinary tract dilation (e.g., hydronephrosis)
• Oligohydramnios, anhydramnios, or polyhydramnios
• Abnormalities in kidney number, structure, or location
• Ureterocele
• Posterior urethral valves

Diagnostics ^[12]

Evaluation for suspected fetal CAKUT should be performed in consultation with specialists (e.g., maternal fetal medicine, urology, nephrology) and may include:

• Specialized prenatal ultrasound is performed for further evaluation, e.g.: ^[13]
  • Assessment of renal vasculature
  • Identification of anomalies associated with a suspected genetic syndrome
• Fetal MRI: to further evaluate for abnormal or equivocal ultrasound findings ^[9]
• Prenatal genetic testing: to identify associated conditions and for pregnancy planning ^[4]

Management ^[12]

Management is multidisciplinary (e.g., maternal fetal medicine, urology, nephrology, genetics) and may include:

• Monitoring with serial fetal ultrasounds (see also "Prenatal risk stratification and management of UTD")
• Genetic counseling and prenatal genetic testing
• Specialized delivery planning

Indications ^[4][5]

Postnatal evaluation, which is any time from birth through adulthood, is recommended for:

• Equivocal or abnormal findings on prenatal ultrasound
• Assessment of associated conditions and complications (e.g., CKD, recurrent UTI)
• Signs and symptoms of CAKUT (e.g., UTIs)

Diagnostics ^[2][5]

Renal bladder ultrasound ^[2][5]

• Preferred initial imaging for:
  • Postnatal management of prenatal UTD
  • UTIs in children and adolescents (See "Imaging for pediatric UTI")
  • Identifying the underlying cause of CKD ^[8]
• Findings
  • Abnormal kidney number, structure, or location (e.g., ectopic kidney, horseshoe kidney)
  • Urinary tract dilation (hydronephrosis, hydroureter)

Additional diagnostics ^[2][5]

The following may be indicated depending on clinical presentation.

• Laboratory studies
  • Kidney function testing (e.g., serum creatinine) and urinalysis: to assess for complications ^[2]
  • Genetic testing: if genetic syndromes are suspected ^[4]
• Advanced imaging ^[14][15]
  • Voiding cystourethrogram or voiding urosonography: to assess for VUR and/or urethral abnormalities
  • CT or magnetic resonance urography: for further characterization of urinary tract anatomy
  • Nuclear medicine renal studies: to assess renal function, cortical integrity, and urinary drainage patency

Management ^[2]

Based on the type of anomaly and severity of the condition, specialists (e.g., nephrology, urology) may provide the following:

• Monitoring and surveillance
  • Pediatric growth
  • Blood pressure
  • Serum creatinine and urine protein
  • Repeat imaging
  • For clinical features of UTI
• Supportive care
  • Antibiotics for acute infections (e.g., treatment of UTIs) and/or prophylaxis (e.g., management of VUR)
  • Clean intermittent catheterization for impaired bladder emptying ^[16]
  • Management of hypertension
  • Management of chronic kidney disease
• Surgical interventions may be indicated for structural abnormalities, e.g.:
  • Pyeloplasty for UPJ obstruction ^[16]
  • Ureteral reimplantation for severe VUR ^[17]
  • Valve ablation for posterior urethral valves ^[18]

Severe bladder outlet obstruction or severe dilation requires urgent referral to a specialist for possible surgical intervention. ^[19]

• Acquired causes of urinary tract obstruction
• Inherited cystic kidney disease, e.g., polycystic kidney disease ^[20]
• Medullary sponge kidney
• Transient prenatal urinary tract dilation
• Floating kidney
  • Description
    • Downward displacement of the kidney due to reduced perirenal fat (thin individuals, anorexia nervosa)
    • Hypermobility of the kidney
  • Clinical features
    • Flank and lower abdominal pain with exacerbation in upright position (nephroptosis causes painful strain)
    • Alleviation of pain in supine position
  • Diagnostics
    • Renal ultrasound in upright and supine position
    • Intravenous pyelogram in upright and supine position
  • Treatment
    • Conservative: abdominal muscle training and stabilization with abdominal wall binders
    • Surgical: laparoscopic nephropexy

References: ^[21]

The differential diagnoses listed here are not exhaustive.