What are the causes of nephrotic syndrome?
Nephrotic syndrome is classified into primary (or idiopathic) and secondary causes.
There are four principal primary etiologies of nephrotic syndrome:
1. Minimal change nephrotic syndrome (MCNS)
2. Focal segmental glomerulosclerosis (FSGS)
3. Membranous nephropathy (MN)
4. Membranoproliferative glomerulonephritis (MPGN)
There are variants of MCNS characterized by subtle changes in mesangial cell hypercellularity or the deposition of specific immunoglobulins such as IgM. However, the clinical significance of these entities is unclear.
In adults, IgA nephropathy, fibrillary, and immunotactoid glomerulonephritis can present with nephrotic syndrome.
The secondary causes of nephrotic syndrome include:
• Post-infectious glomerulonephritis
• Systemic lupus erythematosus
• Henoch-Schoenlein purpura
• Medications
• Infections (e.g., hepatitis B, hepatitis C, HIV)
• Malignancies (Hodgkin’s diseases)
• Amyloidosis
• Diabetes
The cause of primary nephrotic syndrome is generally unknown.
In MCNS, an immune-mediated mechanism has been proposed based on the association of the disease with atopy, various malignancies, and the response to immunosuppressive medications.
In addition, a variety of permeability factors, including vascular endothelial growth factor and interleukin-8, presumably derived from immunoeffector cells, have been linked to proteinuria. Genetic mutations (see below) are increasingly recognized as the cause of primary MCNS and FSGS.
The pathogenesis of idiopathic MN is linked to the development of antibodies to M-type phospholipase A2 receptor and thrombospondin type-1 domain-containing 7A. Infants and young children may develop MN because of antibodies to bovine albumin. Types I and III MPGN are immune-complex disorders, while type II disease (DDD, dense deposit disease) is associated with abnormal regulation of the alternative pathway of complement.
