Congenital anomalies of kidney and urinary tract

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Congenital anomalies of kidney and urinary tract (CAKUT) is a group of abnormalities affecting the kidneys or other structures of the urinary tract. The additional parts of the urinary tract that may be affected include the bladder, the tubes that carry urine from each kidney to the bladder (the ureters), and the tube that carries urine from the bladder out of the body (the urethra). CAKUT results from abnormal development of the urinary system and is present from birth (congenital), although the abnormality may not become apparent until later in life.

Individuals with CAKUT have one or more kidney or urinary tract abnormalities. For paired structures, like the kidneys and ureters, one or both may be affected. Many different developmental abnormalities are classified as CAKUT, including underdevelopment or absence of a kidney (renal hypodysplasia or agenesis), a kidney formed of fluid-filled sacs called cysts (multicystic dysplastic kidney), buildup of urine in the kidneys (hydronephrosis), an extra ureter leading to the kidney (duplex kidney or duplicated collecting system), a blockage in a ureter where it joins the kidney (ureteropelvic junction obstruction), an abnormally wide ureter (megaureter), backflow of urine from the bladder into the ureter (vesicoureteral reflux), and an abnormal membrane in the urethra that blocks the flow of urine out of the bladder (posterior urethral valve).

CAKUT varies in severity. The abnormalities can result in recurrent urinary tract infections or a buildup of urine in the urinary tract, which may damage the kidneys or other structures. Severe CAKUT can result in life-threatening kidney failure and end-stage renal disease.

CAKUT is often one of several features of a condition that affects multiple body systems (syndromic CAKUT). For example, renal coloboma syndrome, 17q12 deletion syndrome, renal cysts and diabetes (RCAD) syndrome, Fraser syndrome, Townes-Brocks syndrome, and branchio-oto-renal syndrome can cause kidney or urinary tract abnormalities in addition to other problems. However, urinary system abnormalities sometimes occur without other signs and symptoms, which is known as nonsyndromic or isolated CAKUT.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

The causes of CAKUT are complex. It is likely that a combination of genetic and environmental factors contribute to the formation of kidney and urinary tract abnormalities.

The genetic factors involved in most cases of CAKUT are unknown. Syndromic CAKUT is caused by changes in the genes associated with the particular syndrome. Variations in these same genes can also underlie some cases of isolated CAKUT. The genes most commonly associated with isolated CAKUT are PAX2, which is also associated with renal coloboma syndrome, and HNF1B, which is involved in 17q12 deletion syndrome and RCAD syndrome. These two genes play critical roles in the formation of the kidneys, urinary tract, and other tissues and organs during embryonic development. Certain mutations in these genes are thought to disrupt development of the kidneys or other parts of the urinary tract before birth, leading to CAKUT. Mutations in many other genes involved in development of the urinary system have also been associated with isolated or syndromic CAKUT.

Research shows that the same genetic mutation can lead to different kidney or urinary tract abnormalities, even among members of the same family. It is likely that additional changes in other genes help determine how the condition develops and how severe it is. In addition, environmental factors may influence development of CAKUT. The risk of CAKUT is higher in babies whose mothers had diabetes; took certain medications that are harmful to the kidneys, such as some anti-seizure drugs; or lacked certain vitamins and minerals, such as folate and iron, during pregnancy.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

Inheritance of CAKUT is complex and not completely understood. About 10 to 20 percent of cases are thought to occur in families. When inherited, CAKUT most commonly follows an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause an abnormality. However, some people who have the altered gene never develop CAKUT, a situation known as reduced penetrance.

Less commonly, CAKUT follows an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not have signs or symptoms of the condition.

In many cases, the inheritance pattern is unknown or the condition is not inherited. In some of these cases, a new (de novo) mutation in the gene that occurs during the formation of reproductive cells (eggs or sperm) in an affected individual's parent or in early embryonic development may underlie the urinary system abnormality. These cases occur in people with no history of the disorder in their family.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

CAKUT is estimated to occur in 1 in 100 to 500 newborns. These abnormalities are the most common cause of end-stage renal disease in children.

Which doctor should you see?

The suggested department for discussing Congenital anomalies of kidney and urinary tract is Urology, with a urologist as the relevant type of clinician. General physician / Family Medicine; paediatrician for children. Referral depends on symptoms.

Additional services that may be relevant, depending on the findings, include: Clinical Genetics.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Which urinary or reproductive symptoms need further assessment?
• Could a blockage, structural problem or another cause be involved?
• What are the alternatives if a procedure is suggested?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Congenital anomalies of kidney and urinary tract. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.