Causes of Nephrotic Syndrome: Understanding the Underlying Factors Behind Protein Loss in Urine

Nephrotic syndrome is a complex kidney disorder characterized by the excessive loss of protein—particularly albumin—through the urine, leading to swelling, low blood protein levels, high cholesterol, and other systemic effects. While the exact cause remains unclear in many cases, research suggests that a combination of genetic predisposition, immune system dysfunction, and environmental triggers may play significant roles in its development.

Types of Nephrotic Syndrome and Their Origins

This condition is generally classified into three main categories: congenital, primary (or idiopathic), and secondary nephrotic syndrome. Each type has distinct underlying causes and patient profiles, making accurate diagnosis essential for effective treatment.

Congenital Nephrotic Syndrome: A Genetic Basis

Congenital nephrotic syndrome typically appears in infants within the first few months of life and is largely attributed to inherited genetic mutations. These mutations often affect proteins in the glomerular filtration barrier—especially in podocytes and the basement membrane—compromising the kidney's ability to retain proteins in the bloodstream. Families with a history of early-onset kidney disease are at higher risk, highlighting the importance of genetic screening in suspected cases.

Primary (Idiopathic) Nephrotic Syndrome: Most Common in Children

Primary nephrotic syndrome, also known as idiopathic, accounts for approximately 90% of cases in pediatric populations. Despite extensive study, the precise trigger remains unknown in most instances. It is widely believed to involve an abnormal immune response that damages the glomeruli without any apparent external cause. Minimal change disease is the most frequent pathological finding in children, while focal segmental glomerulosclerosis (FSGS) is more common in adults.

Secondary Nephrotic Syndrome: Linked to Other Medical Conditions

Secondary nephrotic syndrome arises as a complication of other systemic diseases or external factors. Various infections—including Epstein-Barr virus (EBV), cytomegalovirus (CMV), and hepatitis B—can directly impact kidney function and lead to proteinuria. Additionally, autoimmune disorders such as systemic lupus erythematosus (SLE) and vasculitic conditions like Henoch-Schönlein purpura (also known as IgA vasculitis) are well-documented causes.

Other contributing conditions include diabetes mellitus, certain cancers, and prolonged use of specific medications. Identifying these underlying diseases is crucial because treating the root cause can often improve or even resolve the nephrotic symptoms.

Diagnosis and the Path to Accurate Treatment

Because the symptoms of nephrotic syndrome—such as edema, foamy urine, and fatigue—can overlap with other kidney disorders, comprehensive testing is vital. Blood tests, urinalysis, and imaging studies help assess kidney function, while a renal biopsy may be necessary to determine the exact histological pattern and rule out secondary or genetic forms.

Early and accurate diagnosis allows healthcare providers to tailor treatment plans, whether through corticosteroids for minimal change disease, immunosuppressive therapy for FSGS, or targeted management of underlying conditions in secondary cases. Ongoing monitoring and lifestyle adjustments, including dietary changes and blood pressure control, also support long-term kidney health.