Oligomeganephronia

Oligomeganephronia results from arrested development of the metanephric blastema at 14-20 weeks' gestation, with subsequent hypertrophy of glomeruli and tubules in the kidney. This hypertrophy and hyperfiltration results in further nephron injury and sclerosis. Eventually, this progressive loss of nephrons leads to end-stage renal disease (ESRD).

Developmental arrest of the metanephric blastema at 14-20 weeks' gestation causes oligomeganephronia.

Although oligomeganephronia is associated with some genetic syndromes, most cases of oligomeganephronia are sporadic. However, mutations in the paired-box transcription factor (PAX2) have been seen even in persons with nonsyndromic oligomeganephronia. Heterozygous PAX2 mutations have been detected in one third of children with oligomeganephronia.[1] Mutations in the homeobox transcription factor (hepatocyte nuclear factor-1 β) have been described in association with oligomeganephronia. Interestingly, the heterozygous mutation may be associated with development of the kidney lesion.

Vascular abnormalities and accidents have been associated with this type of renal hypoplasia. The cause of most oligomeganephronia cases is unknown.

Transcription factor 2 (TCF2) is responsible for numerous malformations that involve the kidneys.[2]

United States statistics

The exact frequency of oligomeganephronia is difficult to determine. This condition cannot reliably be clinically distinguished from simple hypoplasia or hypoplasia with dysplasia unless the entire kidney is examined after nephrectomy or at autopsy. In the US Renal Data System, all hypoplasias and dysplasias are reported in a single category that accounts for 8.9% of pediatric ESRD. Incidence of end-stage renal failure due to all causes is 15 per 1 million population of persons younger than 20 years.

International statistics

Oligomeganephronia has been primarily reported in France; however, it has also been described in other geographic areas.

Race-, sex-, and age-related demographics

Renal hypoplasia and dysplasia may occur in people of any ethnic background. The US Renal Data System reports that 70.5% of children in this category are White. International studies have shown a male-to-female ratio of 3:1.[3]

No sex predominance has been reported, although the US Renal Data System shows a slight male predominance (61.3%) for the hypoplasia and dysplasia category.

Oligomeganephronia may be suspected prenatally or at any time after birth.

Oligomeganephronia is progressive and results in chronic renal failure and end-stage renal disease (ESRD).

Morbidity/mortality

Oligomeganephronia is a progressive disorder, eventually resulting in chronic renal failure and ESRD. As with all such disorders, complications such as growth failure, metabolic bone disease, anemia, metabolic acidosis, and other disorders of fluid and electrolyte metabolism may occur.

Complications

Complications of chronic renal disease include growth failure, metabolic bone disease, anemia, metabolic acidosis, and other disorders of fluid and electrolyte metabolism.

Patients with oligomeganephronia and their parents or caregivers need to understand the chronic progressive nature of this condition and the need for long-term follow-up care to maximize growth and to prolong renal function.

If an associated syndrome is present, offer genetic counseling and education to the patient and family.

In neonates, kidney disease is often suspected with spontaneous pneumothorax, feeding problems, or laboratory finding abnormalities.

Oligomeganephronia is usually found in infants in their first year of life and presents with anorexia, vomiting, and failure to thrive.

After the first year of life, individuals with oligomeganephronia most often present with short stature, polyuria and polydipsia, or proteinuria.

This condition may be incidentally diagnosed when renal abnormalities are discovered during the course of another illness.

Physical examination findings are frequently normal in children with oligomeganephronia.

In neonates with oligomeganephronia, particular attention should be directed to diagnosis of associated syndromes, including branchiootorenal syndrome, acrorenal syndrome, and tapetoretinal dystrophia.

• Branchiootorenal syndrome is an autosomal dominant disorder that includes preauricular sinus or dimples, abnormally formed ears, branchial fistula, and hearing loss.

• Acrorenal syndromes may occur sporadically or in an autosomal recessive manner; these include ectrodactyly and urinary tract malformations.

• Tapetoretinal dystrophia occurs more frequently with nephronophthisis but has been described with oligomeganephronia.

Laboratory studies include the following:

• Urinalysis: Proteinuria is often the first laboratory manifestation of oligomeganephronia and precedes decline in renal function by several years.

• Electrolyte, BUN, and creatinine tests: Laboratory manifestations of renal failure are frequently present, including elevated BUN and creatinine levels, hyponatremia, and metabolic acidosis.

• Calcium, phosphorus, alkaline phosphatase, and parathyroid hormone assessments: Advancing renal failure may result in secondary hyperparathyroidism.

• Hemoglobin or hematocrit level: Advancing renal failure may result in anemia due to erythropoietin deficiency.

Imaging studies include renal ultrasonography (see the image below).

Renal sonogram of a newborn with spontaneous pneumothorax, preauricular pits, and branchial cysts. The right kidney was absent, and the left kidney was hyperechoic and hypoplastic. The left kidney's length measured 1.8 cm; kidneys in newborns are normally 4.5 cm.

Small kidney size depicted on ultrasonogram usually establishes diagnosis of hypoplasia.

Follow-up of renal growth has not been demonstrated to be predictive of outcome.

The American College of Radiology has established guidelines regarding imaging studies in renal failure.[4]

If specific syndromes are suspected, the following may be useful:

• Hearing tests

• Ophthalmologic evaluation

• Chromosomal studies

Exhaustive histologic examination of the kidney is the only way to establish an absolute diagnosis of oligomeganephronia.

The number of glomeruli is reduced, and the number of glomerular generations varies from 2-6 (normally ≥ 10).

Existing glomeruli and tubules are enlarged, and glomerular diameters of 300-400 nm are common.

As the disease progresses, segmental sclerosis and hyalinosis of glomeruli are present.

Tubular atrophy with interstitial fibrosis occurs.

Medical care in patients with oligomeganephronia is supportive, including fluid and electrolyte balance, nutritional support, and management of the manifestations of chronic renal failure.

Treatment with angiotensin-converting enzyme inhibitors may be of benefit in slowing progression.[5, 6, 7]

Consultation

Once diagnosis of renal hypoplasia is suspected or established based on renal ultrasonography findings, refer patients to a pediatric nephrologist for ongoing management of chronic renal failure.

Diet

Dietary recommendations depend on the degree of renal functional impairment.

Most patients with oligomeganephronia have renal salt wasting and require no restriction of dietary salt or water.

As renal failure advances, potassium and phosphorus level balance may become problematic and require dietary restrictions.

Activity

In general, no restriction of normal activity is required. Advise patients with oligomeganephronia to maintain an active, healthy lifestyle.

Long-term follow-up care

Oligomeganephronia is a chronic progressive renal disease that leads invariably to renal failure.

Assessment of renal function, biochemical status, and growth is necessary to manage this condition and to provide optimal care.

Fuke et al reported a case of a 23-year-old man with oligomeganephronia that did not progress to end-stage renal failure. Clinical features included renal insufficiency, persistent proteinuria, and bilateral small kidneys. Renal pathology revealed greatly enlarged glomeruli (mean diameter, 325 μm, which was approximately 2 times larger than normal).[8]

Treatment of oligomeganephronia is generally supportive and directed at maintaining normal biochemical balance, hemoglobin, and growth.

In addition, ACE inhibitors may be of benefit in slowing progression of renal failure, even if the patient has a normal blood pressure. Although ACE inhibitors are mentioned as a potential treatment, they have not been studied sufficiently to provide dosing guidelines.