Nephrotic Syndrome Diagnosis and Management

Primary (Idiopathic) Glomerular Diseases

The American College of Cardiology is not applicable here, however, Minimal Change Disease (MCD) is the most common cause in children under 12 years, accounting for the majority of pediatric cases 2
Focal Segmental Glomerulosclerosis (FSGS) can be further classified into four subclasses: Primary FSGS, Genetic FSGS, Secondary FSGS, and FSGS of undetermined cause 3, 4, 1
Membranous Nephropathy (MN) is now proven to be an autoimmune disease with pathogenic autoantibodies targeting podocyte antigens, and is the most common primary cause in white adults 1, 5

Systemic Lupus Erythematosus, particularly Class V membranous lupus nephritis, is a secondary cause of nephrotic syndrome 1
Solid Tumors can cause paraneoplastic glomerular disease 1
Viral Infections, including HIV, can trigger infection-related glomerulonephritis 1, 5, 6
Cancer Therapies, such as targeted agents and immunotherapies, may cause podocytopathies 1
Anti-Angiogenesis Drugs are associated with proteinuria and lesions such as minimal change disease/FSGS 1
Immune Checkpoint Inhibitors can cause nephrotic syndrome 1
Other Medications, such as drug-induced glomerular injury, can manifest as secondary FSGS or membranous nephropathy 5

Familial Kidney Disease, patients with family history of nephrotic syndrome, should undergo genetic testing 1, 5
Syndromic Features, patients presenting with extra-renal manifestations, should undergo genetic testing 1, 5
Steroid-Resistant FSGS, 11-24% of adults with steroid-resistant nephrotic syndrome and FSGS on biopsy will have disease-causing variants, primarily in type IV collagen or podocyte genes 5
Early-Onset Disease, consider genetic testing in early-onset cases 5
Common Genetic Mutations, such as NPHS1, NPHS2, WT1, and PLCE1, are associated with congenital nephrotic syndrome 5

Children Under 12 Years, initial treatment with glucocorticoids without biopsy is standard, as MCD is the most common cause 2
Children Over 12 Years and Adults, kidney biopsy is required to determine underlying cause, except in cases with positive serum anti-phospholipase A2 receptor antibodies (diagnostic of membranous nephropathy) 2, 1
Evaluate for Secondary Causes, comprehensive workup to exclude systemic diseases, infections, malignancies, and drug-induced causes 7, 1
Consider Genetic Screening, where appropriate, particularly in familial cases, syndromic features, or steroid-resistant disease 3, 1