Renal Agenesis: Symptoms, Types, Causes and Treatment

Renal agenesis is a congenital condition in which one or both kidneys fail to develop. As one of the most significant congenital anomalies of the urinary tract, it can have a profound impact on health—sometimes going unnoticed, other times resulting in life-threatening complications. Understanding the symptoms, types, causes, and available treatments is crucial for both patients and healthcare providers. This article synthesizes the latest research and clinical insights to provide a comprehensive overview of renal agenesis.

Symptoms of Renal Agenesis

Renal agenesis often presents a diagnostic challenge. Many individuals may remain asymptomatic, while others may experience symptoms that overlap with various other medical conditions, leading to delayed or incorrect diagnoses. Recognizing the range of symptoms is vital for early detection and management.

Symptom	Population	Frequency	Source(s)
Abdominal Pain	Adolescents/Adults	Common in OHVIRA, URA	1 16
Urinary Issues	Adolescents/Adults	Frequent (e.g., infection, UTI, incontinence)	1 7
Infertility	Females	Possible, especially with Müllerian anomalies	1 16
Hypertension	All ages	~16% in URA	7
Micro-albuminuria	All ages	~21% in URA	7
Asymptomatic	All	Some cases (incidental finding)	1 7
Acute Abdomen	Adolescents	More common in younger patients	1
Foul-smelling Vaginal Discharge	Females (OHVIRA)	Present in some	1 16

Table 1: Key Symptoms

Common Presentations

Symptoms of renal agenesis depend on whether the condition is unilateral (one kidney missing) or bilateral (both kidneys missing), and whether other organs are affected.

• Unilateral Renal Agenesis (URA):

  • Many individuals are asymptomatic and discover the condition incidentally during imaging for other reasons 1 7.
  • When symptoms occur, they often include abdominal or flank pain, urinary tract infections, or hypertension. Over time, the solitary kidney may show signs of stress, such as micro-albuminuria, reduced filtration rate, or even chronic kidney disease 7.
  • In females, particularly those with associated Müllerian duct anomalies (such as OHVIRA syndrome), symptoms can include pelvic pain, abnormal menstrual bleeding, or vaginal discharge 1 16.

• Bilateral Renal Agenesis (BRA):

  • This condition leads to an absence of both kidneys and is usually fatal shortly after birth due to severe oligohydramnios (low amniotic fluid), leading to underdeveloped lungs (pulmonary hypoplasia) and characteristic physical features (Potter sequence) 12 13.

Associated Anomalies and Complications

• Associated Genitourinary Anomalies:

  • URA may be linked with other urinary tract abnormalities (e.g., vesicoureteral reflux, dilated ureter) or anomalies in the reproductive organs (e.g., absence of vas deferens, uterine anomalies) 5 7 16.
  • In syndromic forms like OHVIRA, symptoms are often gynecological (e.g., primary infertility, abnormal bleeding) 1 16.

• Renal Injury and Long-term Effects:

  • Patients with a single kidney are at increased risk for hypertension and kidney injury. Regular monitoring is advised, as up to 10% may develop significantly reduced kidney function (GFR <60 mL/min/1.73 m²) 7.

• Incidental Findings:

  • With the increasing use of prenatal and bedside ultrasound, many cases are detected before symptoms develop, allowing for early monitoring or intervention 1 2.

Types of Renal Agenesis

Renal agenesis can be classified based on the number of kidneys affected and the presence or absence of associated anomalies. Understanding these types helps guide prognosis and management.

Type	Description	Prognosis/Impact	Source(s)
Unilateral (URA)	Absence of one kidney	Often compatible with normal life, but risk of complications	4 7
Bilateral (BRA)	Absence of both kidneys	Lethal without intervention	6 12
Syndromic	Associated with other organ anomalies (e.g., OHVIRA, VATER)	Variable, depends on associated defects	1 5 16
Non-Syndromic	Isolated kidney agenesis	Prognosis depends on kidney function	7 8 9

Table 2: Types of Renal Agenesis

Unilateral Renal Agenesis (URA)

URA, the most common form, is characterized by the absence of one kidney. Most patients lead healthy lives but require regular follow-ups to monitor the function of the remaining kidney. Males are slightly more commonly affected 4 7. About one-third of patients have additional urinary tract or extra-renal anomalies, such as vesicoureteral reflux or reproductive tract malformations 7.

Bilateral Renal Agenesis (BRA)

BRA, or Potter syndrome, is much rarer but almost always fatal without advanced intervention. The absence of both kidneys leads to severe oligohydramnios, pulmonary hypoplasia, and characteristic physical deformities. Historically, survival beyond the newborn period was unheard of, but rare cases of survival with aggressive intervention have been reported 6 12 13.

Syndromic vs. Non-Syndromic Forms

• Syndromic Renal Agenesis:

  • Occurs as part of a broader syndrome, such as VATER association (vertebral, anal, tracheoesophageal, renal, and limb anomalies), Fraser syndrome, or OHVIRA syndrome (uterus didelphys, obstructed hemivagina, and ipsilateral renal agenesis) 1 5 8 16.
  • These forms often present with complex clinical pictures, requiring multidisciplinary management.

• Non-Syndromic Renal Agenesis:

  • Isolated kidney agenesis, with no other organ involvement, can still pose risks for long-term renal health 7 8 9.

Causes of Renal Agenesis

Understanding the origins of renal agenesis requires exploring both genetic and developmental factors. Recent advances in genetics have shed light on mechanisms that disrupt normal kidney formation.

Cause Category	Mechanism/Factor	Key Genes/Pathways	Source(s)
Developmental	Malformation of ureteric bud or metanephric blastema	RET, ITGA8, GFRA1, GREB1L, FRAS1, FREM2	2 3 6 8 9 10 11
Genetic	Single-gene mutations, inherited or de novo	ITGA8 (recessive), GFRA1, GREB1L, FRAS1, FREM2	3 6 8 9 10
Multifactorial	Combination of genetic and environmental influences	Variable	2 11
Syndromic	Association with broader genetic syndromes	VATER, Fraser syndrome	5 8 11

Table 3: Causes of Renal Agenesis

Developmental Pathways

Kidney development hinges on the interaction between the ureteric bud and the metanephric mesenchyme. Disruptions in this reciprocal induction can halt kidney formation, resulting in agenesis 2 11.

• Failure of Ureteric Bud Induction: The most common cause is the failure of the ureteric bud to induce the metanephric blastema, leading to absent kidney structures 2 5.

• Regression of Multicystic Dysplastic Kidneys: In some cases, a kidney may begin to form but subsequently involute and disappear in utero, mimicking agenesis 2.

Genetic Contributions

Recent genomic studies have identified several key genes:

• ITGA8: Recessive mutations can cause bilateral renal agenesis by preventing kidney development 3.
• GFRA1: Biallelic loss-of-function mutations in this gene are linked to lethal BRA 6.
• GREB1L: Variants are implicated in both bilateral and unilateral forms, affecting urogenital development 9 10.
• FRAS1 and FREM2: Mutations here can cause syndromic and non-syndromic CAKUT, including renal agenesis 8.
• RET: Implicated in a minority of BRA cases 3.

These genes play roles in signaling pathways essential for early kidney and urinary tract development. Inheritance patterns can be autosomal dominant, autosomal recessive, or de novo (sporadic) 3 6 8 9 11.

Multifactorial and Environmental Factors

Not all cases are explained by single-gene mutations. Many are likely multifactorial, involving complex interactions between genes and environmental exposures. Some cases remain unexplained, highlighting the need for further research 2 11.

Syndromic Associations

Renal agenesis can also be part of broader syndromes with known genetic backgrounds, such as Fraser syndrome (FRAS1/FREM2 mutations) or OHVIRA syndrome (Müllerian duct anomalies) 1 8 16.

Treatment of Renal Agenesis

Management strategies depend on whether one or both kidneys are absent, the presence of symptoms, and associated anomalies. While some patients require only routine monitoring, others may need complex, multidisciplinary care.

Treatment Approach	Indication	Outcome/Goal	Source(s)
Monitoring & Follow-up	Asymptomatic URA	Preserve single kidney health	7
Blood Pressure & Renal Function Control	URA with renal injury/hypertension	Prevent progression	7
Surgical Correction	Associated anomalies (e.g., OHVIRA)	Symptom relief, fertility preservation	1 16
Dialysis & Transplant	BRA (rare survivors)	Life-sustaining therapy	12 13
Serial Amnioinfusion	Fetal BRA (experimental)	Prevent pulmonary hypoplasia, enable survival	12 13 14 15

Table 4: Treatment Approaches

Unilateral Renal Agenesis: Management and Follow-up

For those with a single kidney and no symptoms, management is typically conservative:

• Regular Monitoring:
  • Annual assessment of blood pressure, urine protein (micro-albuminuria), and kidney function is recommended 7.
• Education:
  • Patients and families should be advised to avoid activities or exposures that may harm the remaining kidney (e.g., nephrotoxic medications, certain contact sports).
• Addressing Associated Anomalies:
  • If other urinary or reproductive tract anomalies are present, targeted interventions may be needed 1 5 7.

Surgical Treatment for Syndromic Forms

• OHVIRA Syndrome:
  • The mainstay of treatment is minimally invasive surgery to remove obstructive vaginal septa and restore normal anatomy, preserving fertility and improving symptoms 1 16.
  • Vaginal or laparoscopic approaches are preferred; open surgery is reserved for select cases 16.

Bilateral Renal Agenesis: Experimental and Supportive Approaches

BRA is historically fatal, but novel interventions are under investigation:

• Serial Amnioinfusion:

  • Repeated amniotic fluid infusions during pregnancy can reduce the risk of lung hypoplasia by restoring amniotic fluid volume 12 13.
  • Isolated reports document survival into infancy when combined with immediate dialysis and planned kidney transplantation 12.
  • However, this approach is experimental, its long-term efficacy is unclear, and it is associated with significant ethical and practical challenges 13 14 15.

• Neonatal Intensive Care and Renal Replacement Therapy:

  • For rare survivors, immediate peritoneal dialysis is initiated as a bridge to kidney transplantation 12 13.
  • Success is highly variable, and outcomes depend on pulmonary function, infection risk, and transplant eligibility.

Ethical and Cost Considerations

• Ethical Debates:
  • Innovations like serial amnioinfusion raise complex ethical issues, including consent, balancing risks and benefits, and resource allocation 14.
• Cost-Effectiveness:
  • Modeling studies suggest that serial amnioinfusion can be cost-effective under certain conditions, especially if survival to transplant and quality of life after transplantation are adequate 15.

Conclusion

Renal agenesis is a complex developmental disorder with a wide spectrum of presentations, outcomes, and management strategies. Early recognition, appropriate monitoring, and individualized care are essential to optimize outcomes. Here are the key points to remember:

• Symptoms are variable: Many individuals with unilateral agenesis are asymptomatic, but others may develop pain, infections, hypertension, or reproductive issues 1 7 16.
• Types matter: Unilateral agenesis is usually compatible with life, while bilateral agenesis is typically fatal unless experimental interventions are successful 4 6 12.
• Genetics are key: Both single-gene mutations and multifactorial mechanisms can cause renal agenesis. Advances in genomics are improving our understanding of these pathways 3 6 8 9 10 11.
• Treatment is tailored: Most with unilateral agenesis require monitoring; those with syndromic forms or complications may need surgery. Bilateral agenesis management remains challenging, with experimental therapies still under investigation 7 12 13 14 15 16.
• Lifelong follow-up is critical: Early detection and regular assessment can help preserve health in affected individuals and identify complications early 7.

Renal agenesis illustrates the intersection of developmental biology, genetics, and clinical care—highlighting the importance of collaboration and ongoing research to improve outcomes for affected individuals and families.