Congenital and infantile nephrotic syndrome

As early as the mid-1980s, intensive medical therapy with subsequent kidney transplantation was established as the treatment method of choice for severely ill infants (Hölttä 2020).

See also congenital nephrotic syndrome

Congenital and infantile nephrotic syndrome is defined as a triad of proteinuria > 200 mg / mmol creatinine, hypoalbuminemia and edema (Reynolds 2019). It typically occurs between the 4th - 12th month of life (Dötsch 2017).

See also congenital nephrotic syndrome

Congenital and infantile nephrotic syndrome is a special form of nephrotic syndrome alongside congenital nephrotic syndrome. It is only possible to differentiate between the two diseases based on the age of onset (Dötsch 2017).

See also congenital nephrotic syndrome

The incidence of congenital nephrotic syndrome of the Finnish type is 0.5 - 1:100,000 worldwide, but 1:10,000 in Finland (Manski 2024). I have no specific figures on the incidence of juvenile NS.

The main cause is mutations of the NPHS2 gene (Manski 2024), less frequently NPHS1 (Schwenger 2014).

See also congenital nephrotic syndrome

The genetic defect primarily affects the protein nephrin. This is of great importance for the structure of the slit diaphragm (Keller 2002).

The proteinuria leads to:

1. albuminuria
2. edema
3. hypoalbuminemia
4. hyperlipidemia
5. Increased platelet aggregation
6. Loss of minerals and vitamins with malnutrition and increased risk of infection
7. Loss of thyroid-binding globulin in the urine with the occurrence of hypothyroidism (Jain 2023)

Congenital and infantile nephrotic syndrome typically only manifests after the 3rd month of life up to a maximum of 12 months of age (Herold 2018).

If the disease manifests earlier (within the first 3 months of life), it is referred to as congenital nephrotic syndrome. Both syndromes are caused by different diseases:

• Diffuse mesangial sclerosis
• Congenital nephrotic syndrome of the Finnish type
• Congenital syphilis, toxoplasmosis, rubella, HIV, cytomegaly
• Idiopathic nephrotic syndrome
• Galloway syndrome
• Mercury intoxication (Keller 2010).

The main feature of the disease is a significant leakage of plasma proteins (AbuMaziad 2021).

The infants develop oedema from the age of 3 months due to the high proteinuria (Keller 2010).

If left untreated, terminal renal failure occurs between the ages of 3 and 8 (Keller 2010).

There are additional symptoms such as:

• Poor nutritional status
• Hypothyroidism
• Thromboembolic complications
• Hypogammaglobulinemia (Keller 2010).

The edema occurring in infancy and failure to thrive are the most conspicuous features (Manski 2024). Sonography shows a change in the kidneys typical of the disease (see below) (Hofmann 2005).

The invasive kidney biopsy previously used for diagnosis is therefore rarely necessary nowadays (Boyer 2021) and is only recommended in unclear cases (Manski 2024).

See also congenital nephrotic syndrome

Sonography

Sonography shows a clear enlargement of the kidneys, which have an increased echogenicity compared to the liver (Hofmann 2005).

• Large glomerular proteinuria
• Hypalbuminemia
• Normal complement levels (Schwenger 2014)

Another form of juvenile NS histologically is diffuse mesangial sclerosis. In this disease, pseudohermaphroditism masculinus and / or a Wilms tumor are found in around 30% of those affected. This syndrome is also known as Denys-Drash syndrome (Claßen 2024). The mode of inheritance is autosomal dominant, there is a mutation of the NPHS1 gene (11p13) (Dötsch 2017).

See also congenital nephrotic syndrome

Congenital nephrotic syndrome (this typically occurs in the first 3 months of life [Herold 2018]).

The affected patients are prone to:

• Hemodynamic disturbances
• thromboses
• infections
• Growth disorders
• Renal failure (Boyer 2021)

It is recommended that children with juvenile NS be referred to a specialized pediatric nephrology unit as soon as possible (Boyer 2021).

The treatment consists of:

• Good nutrition
• Albumin infusions
• Unilateral or bilateral nephrectomy may be required for severe proteinuria
• Drug therapy for the edema
• Kidney transplantation or dialysis (Manski 2024)

Congenital infantile nephrotic syndrome is typically characterized by resistance to glucocorticoids (Dötsch 2017). Immunosuppressants are also ineffective (Manski 2024).

ACE inhibitors and indomethacin can be used to reduce protein excretion via the kidneys (Jain 2023).

Hypothyroidism, if present, should be started with 6.25 to 12.5 mcg and then adjusted to the TSH value (Jain 2023).

Aspirin or dipyridamole are recommended for anticoagulation (Jain 2023).

There is no information on the prognosis of juvenile NS in particular.

According to a Finnish study, the average survival time for congenital nephrotic syndrome between 1965 and 1973 was only 7.6 months. Later, an aggressive treatment regimen with early nephrectomy, transplantation and dialysis was used. As a result, over 90% of children treated in this way showed similar overall survival rates to other transplanted children (Boyer 2021). The graft survival rate is >. 80 % (Jain 2023).

The prognosis of a CNS caused by infection, on the other hand, is good (Jain 2023)

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