There are many possible causes of nephrotic syndrome. These are usually related to a health condition that has the potential to cause damage to the glomerulus and affect the functioning of the kidneys.
In healthy individuals, large protein molecules cannot be filtered from the blood and into the kidneys through the glomerulus. However, the health conditions that can cause nephrotic syndrome alter this process and allow some of the protein molecules to pass through to be excreted in the urine.
Minimal Change Disease
Minimal change disease is the most common cause of nephrotic syndrome in children, accounting for approximately 90% of cases in children less than five years of age. In contrast, it is the cause of approximately 20% of cases in adults.
This disorder involves abnormal function of the kidneys, despite no significant changes to the kidney tissue upon microscopic examination. The cause of minimal change disease and abnormal kidney function is not known, although it has been suggested that it is linked to a minor change in the immune system. This type of disease has a good response to steroid medication and does not commonly cause kidney failure.
It is also known as membranous nephritis. It is the most common cause of nephrotic syndrome in adults and is uncommon in children.
This condition involves thickening of the glomerulus membrane, which results in some protein leaking through into the kidneys. This change in the membrane is visible when a tissue sample from a biopsy is examined under a microscope. The cause of membranous glomerulonephritis is not clear, although there are several conditions and medications associated with its development. These associated conditions include hepatitis B, malaria, lupus, and cancer.
Focal Segmental Glomerulosclerosis
Focal segmental glomerulosclerosis accounts for approximately 10% of cases in children and a high proportion of adult with nephrotic syndrome. It involves the formation of small scars on some areas of the glomeruli, known as sclerosis. It is not known why this occurs, although it may be linked to a reaction of the immune system to an infection or other stimulus.
Other Glomerular Disorders
Additional, there are many other kidney disorders that may sometimes be responsible for causing nephrotic syndrome. These may include:
- Membranoproliferative glomerulonephritis
- Mesangial proliferative glomerulonephritis
- Fibrillary glomerulosclerosis
- Diffuse mesangial sclerosis
- IgM mesangial nephropathy
In many cases, the cause of these conditions cannot be established, although it is assumed to be associated with an immune response that causes damage to the glomeruli.
Other Health Conditions
Nephrotic syndrome may also occur as a complication linked to various other conditions that are not directly related to the kidney function. These potential causes include:
- Diabetic nephropathy
- Systemic lupus erythematosus (SLE)
- Multiple myeloma
- Rheumatoid arthritis
- Infections (e.g. hepatitis or mononucleosis)
- Blood clot
- Heart failure
Certain immune and genetic disorders may also predispose an individual to symptoms of nephrotic syndrome.
Medications and Toxins
Some medications such as non-steroidal anti-inflammatory medications have the potential to cause nephrotic syndrome. The risk of this occurring increases significantly when certain medication combinations are used and, therefore, these combinations should be avoided where possible. Various poisons or toxins may also cause the condition in some cases.
Reviewed by Susha Cheriyedath, MSc