Nephrotic syndrome is caused by various disorders which damage the kidneys, particularly to the basement membrane of the glomerulus. This immediately causes abnormal excretion of protein in the urine.

The most common cause in children is minimal change disease, while membranous glomerulonephritis is the most common cause in adults.

This condition can also occur as a result of infection, drug exposure, malignancy, hereditary disorders, immune disorders, or diseases that affect multiple body systems including diabetes, systemic lupus erythematosus, multiple myeloma, and amyloidosis. It can accompany kidney disorders, including glomerulonephritis, focal and segmental glomerulosclerosis and mesangiocapillary glomerulonephritis.

Nephrotic syndrome can affect all age groups. In children, it is most common from age 2 to 6. Males are slightly more likely to be affected than females.