What is the most common cause of nephrotic syndrome in children?

From the Guidelines

The most common cause of nephrotic syndrome in children is Minimal Change Disease (MCD), accounting for more than 75% of all pediatric cases and for 90% of cases in children under 5 years of age. This condition is characterized by normal-appearing glomeruli under light microscopy but shows foot process effacement when examined with electron microscopy. MCD typically presents with sudden onset of proteinuria, hypoalbuminemia, edema, and hyperlipidemia - the classic tetrad of nephrotic syndrome.

Key Characteristics of MCD

• Normal-appearing glomeruli under light microscopy
• Foot process effacement under electron microscopy
• Sudden onset of proteinuria, hypoalbuminemia, edema, and hyperlipidemia The condition usually responds well to corticosteroid therapy, with most children achieving remission within 2-4 weeks of starting prednisone at a dose of 2 mg/kg/day (maximum 60 mg/day), as recommended by the KDIGO 2021 guideline for the management of glomerular diseases 1.

Treatment Approach

• Daily prednisone for 4-6 weeks followed by alternate-day therapy for another 4-6 weeks
• Total treatment duration of 8-12 weeks, as updated by the KDIGO 2021 guideline 1
• Consideration of glucocorticoid-sparing agents for frequently relapsing or glucocorticoid-dependent patients, such as levamisole or rituximab, as suggested by recent studies 1 The good response to steroids gives this condition its alternative name "steroid-sensitive nephrotic syndrome." The exact cause of MCD remains unclear, but it is believed to involve immune system dysfunction, particularly T-cell abnormalities that affect podocyte function and increase glomerular permeability to proteins, as discussed in the study by Kidney International in 2007 1.

Long-term Prognosis

• Excellent long-term prognosis for most children with MCD
• Approximately 60-80% may experience relapses requiring additional courses of steroid therapy
• Importance of genetic testing to clarify the use of immunosuppressive agents in steroid-resistant cases, as recommended by the KDIGO 2021 guideline 1

From the Research

Causes of Nephrotic Syndrome in Children

• The most common cause of nephrotic syndrome in children is minimal change nephrotic syndrome (MCNS), accounting for 90% of cases under the age of 10 years and more than 50% in older children 2.
• MCNS is characterized by a disorder of T-lymphocytes, which release a cytokine that injures the glomerular epithelial cells, leading to albuminuria 2.
• Other causes of nephrotic syndrome in children include focal segmental glomerulosclerosis (FSGS), which is usually resistant to corticosteroids and carries a significant risk of kidney failure 3.

Characteristics of Minimal Change Nephrotic Syndrome

• MCNS generally responds to corticosteroids, although most patients experience disease relapses 4, 3.
• The disease is characterized by a high rate of relapse, with 70% of children with MCNS having a steroid-dependent or frequent relapsing course of the disease 5.
• The presence of mesangial hypercellularity and glomerular hypertrophy in renal biopsies of patients with MCNS may indicate a higher risk for progressive renal disease 2.

Treatment and Prognosis

• Corticosteroids are considered first-line therapy for the treatment of nephrotic syndrome, with prednisone therapy initiated at doses of 60 mg/m2 per day 4.
• Alternative therapies, such as immunosuppressive medications, may be used to prevent relapses and treat corticosteroid-resistant disease 4, 3.
• The prognosis for children with MCNS is generally good, with most patients achieving remission, although some may require prolonged immunosuppressive treatment 5, 2.