Renal agenesis is a congenital condition where one or both kidneys fail to develop during fetal growth. It is a birth defect that occurs early in pregnancy, affecting the formation of the urinary system. The absence of one or both kidneys significantly impacts the body’s ability to filter waste and maintain fluid balance.
Understanding Agenesis Kidney
Agenesis kidney stems from a developmental failure in the early stages of fetal growth, involving the ureteric bud and the metanephric mesenchyme. Kidney development begins around the fifth week of gestation when the ureteric bud interacts with the adjacent metanephric mesenchyme.
The ureteric bud invades the metanephric mesenchyme, leading to branching events that form the collecting ducts, calyces, and infundibula of the kidney. Simultaneously, the metanephric mesenchyme differentiates into nephrons, the functional filtering units. If the ureteric bud fails to form or properly invade the mesenchyme, the tissue undergoes programmed cell death, leading to the absence of a kidney. This signaling pathway, largely mediated by the Ret/GDNF pathway, is important for kidney formation.
Causes of Kidney Agenesis
Kidney agenesis arises from a combination of genetic and environmental factors. Genetic predispositions play a role, with mutations in certain genes involved in kidney development being identified. For example, the GDNF gene and its receptor Ret are involved in the formation of the ureteric bud and subsequent kidney development. Mutations in genes like PAX2 and RET have been associated with renal agenesis.
Environmental factors during pregnancy can also contribute. Exposure to certain toxins or maternal diabetes during gestation are potential influences. These factors are believed to interfere with kidney development. In some instances, genetic changes causing renal agenesis occur randomly, without any prior family history.
Types and Their Implications
Renal agenesis manifests in two primary forms: unilateral renal agenesis (URA) and bilateral renal agenesis (BRA), each carrying distinct health implications.
Unilateral Renal Agenesis (URA)
Unilateral renal agenesis, where one kidney is missing, is more common, affecting approximately 1 in 1000 to 1 in 2000 live births. Individuals with URA often remain asymptomatic, as the single remaining kidney undergoes compensatory growth to perform the function of both kidneys. Many people with URA lead full lives without knowing they have only one kidney, with diagnosis often occurring incidentally during imaging for other reasons.
Despite compensatory function, individuals with URA face an increased risk of long-term complications. These can include high blood pressure (hypertension) and proteinuria (excess protein in the urine). There is also an elevated risk of developing chronic kidney disease, which may progress to end-stage renal disease requiring dialysis or a kidney transplant later in life. Some children with URA may also have other associated birth defects, such as congenital heart conditions or abnormalities of the genitourinary system.
Bilateral Renal Agenesis (BRA)
Bilateral renal agenesis (BRA), the absence of both kidneys, is a severe condition, estimated to occur in about 1 in 5000 fetuses. This condition is almost always fatal shortly after birth, within a few hours or days. The absence of kidneys means the fetus cannot produce urine, a primary component of amniotic fluid in the womb. A lack of amniotic fluid (oligohydramnios) severely impairs lung development, leading to pulmonary hypoplasia.
Babies born with BRA often present with physical features known as Potter syndrome, including wide-set eyes, a flattened nose, low-set ears, and limb deformities. These result from compression within the uterus due to insufficient amniotic fluid. Underdeveloped lungs are the primary cause of death in these infants, as they cannot support breathing outside the womb. Experimental procedures like serial prenatal amnioinfusion, which involves injecting saline into the amniotic sac, are being explored in clinical trials to improve lung maturation and survival, potentially allowing for supportive care and consideration of peritoneal dialysis as a bridge to kidney transplant.
Diagnosis and Management
Diagnosis of renal agenesis begins with ultrasonography, often during routine prenatal scans around 20 weeks of gestation. Inability to visualize one or both kidneys, along with the absence of a fetal bladder or low amniotic fluid levels, can raise suspicion. Postnatal ultrasound scans confirm the diagnosis. If ultrasound findings are inconclusive, further imaging techniques such as Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) may be used. MRI can be useful in cases of severe oligohydramnios or maternal obesity, which limit ultrasound accuracy.
Management strategies depend on the type and severity of the condition, and any associated anomalies.
Unilateral Renal Agenesis Management
For unilateral renal agenesis, where one kidney is functioning, the focus is on monitoring the remaining kidney and managing potential long-term complications. Regular follow-up appointments are recommended to monitor blood pressure, kidney function, and check for proteinuria. Lifestyle modifications, such as maintaining a healthy diet and regular exercise, are advised to support overall kidney health.
Bilateral Renal Agenesis Management
In cases of bilateral renal agenesis, the prognosis is severe, as the condition is incompatible with life due to underdeveloped lungs. Medical management for BRA centers on comfort care and providing family support. This may involve a perinatal palliative care team to help families make informed decisions regarding their baby’s care at birth, focusing on ensuring the infant is comfortable. While experimental treatments like serial amnioinfusion are being investigated in clinical trials to promote lung development, they are not standard care and carry risks.