What Causes Nephrotic Syndrome in Children?

Nephrotic syndrome is a relatively common kidney disorder in children, characterized by a group of symptoms that result from damage to the glomeruli—the tiny filtering units in the kidneys. While the exact cause of primary nephrotic syndrome remains unclear, researchers believe it is primarily linked to immune system dysfunction that disrupts the integrity of the glomerular filtration barrier.

Understanding the Glomerular Filtration Barrier

Under normal conditions, the glomeruli act as highly selective filters, preventing essential blood components—especially proteins like albumin—from leaking into the urine. This filtration system consists of specialized cells and membranes that maintain precise control over what passes through. However, when the immune system malfunctions, it can trigger inflammation or autoimmune responses that compromise this barrier, increasing its permeability.

How Immune Dysfunction Leads to Protein Loss

Immune-mediated injury damages the structure of the glomerular filter, allowing large amounts of protein—particularly albumin—to escape into the urine. This excessive urinary protein loss, known as proteinuria, leads to hypoalbuminemia, a condition marked by abnormally low levels of albumin in the bloodstream.

The Domino Effect of Low Albumin Levels

Albumin plays a crucial role in maintaining oncotic pressure—the force that keeps fluid within blood vessels. When albumin levels drop, this pressure decreases, causing fluid to shift from the bloodstream into surrounding tissues. This imbalance results in edema, most commonly seen around the eyes, abdomen, and legs in affected children.

Complications Related to Hypoalbuminemia

Beyond swelling, hypoalbuminemia triggers several secondary health issues. As the liver attempts to compensate for low protein levels, it ramps up the production of lipoproteins, often leading to hyperlipidemia—elevated cholesterol and triglyceride levels. Additionally, the concentration of blood due to fluid loss from the vascular space increases the risk of blood clot formation, posing serious circulatory risks.

Genetic Factors in Steroid-Resistant Cases

In some cases, particularly those resistant to standard steroid treatments, nephrotic syndrome stems from genetic mutations. These mutations often affect key structural proteins in the podocytes—specialized cells in the glomeruli—or components of the glomerular basement membrane. Defects in molecules such as nephrin or podocin impair the filtration barrier's function, resulting in persistent protein leakage.

This genetic form typically presents early in life and may progress to chronic kidney disease if not properly managed. Identifying these inherited causes is critical for guiding treatment decisions and providing accurate family counseling.

In summary, while immune dysregulation remains the leading theory behind most pediatric nephrotic syndrome cases, genetic factors play a significant role in more severe or treatment-resistant forms. A deeper understanding of both pathways is essential for improving diagnosis, personalizing therapies, and ultimately enhancing long-term outcomes for children with this complex kidney condition.