Along with obtaining a complete medical history, a series of biochemical tests are required in order to arrive at an accurate diagnosis that verifies the presence of the illness. In addition, imaging of the kidneys (for structure and presence of two kidneys) is sometimes carried out, and/or a biopsy of the kidneys. The first test will be a urinalysis to test for high levels of proteins, as a healthy subject excretes an insignificant amount of protein in their urine. The test will involve a 24-hour bedside urinary total protein estimation. The urine sample is tested for proteinuria (>3.5 g per 1.73 m per 24 hours). It is also examined for urinary casts, which are more a feature of active nephritis. Next a blood screen, comprehensive metabolic panel (CMP) will look for hypoalbuminemia: albumin levels of ≤2.5 g/dL (normal=3.5-5 g/dL). Then a Creatinine Clearance C test will evaluate renal function particularly the glomerular filtration capacity. Creatinine formation is a result of the breakdown of muscular tissue, it is transported in the blood and eliminated in urine. Measuring the concentration of organic compounds in both liquids evaluates the capacity of the glomeruli to filter blood. Electrolytes and urea levels may also be analysed at the same time as creatinine (EUC test) in order to evaluate renal function.

A lipid profile will also be carried out as high levels of cholesterol (hypercholesterolemia), specifically elevated LDL, usually with concomitantly elevated VLDL, is indicative of nephrotic syndrome.

A kidney biopsy may also be used as a more specific and invasive test method. A study of a sample’s anatomical pathology may then allow the identification of the type of glomerulonephritis involved. However, this procedure is usually reserved for adults as the majority of children suffer from minimum change disease that has a remission rate of 95% with corticosteroids. A biopsy is usually only indicated for children that are "corticosteroid resistant" as the majority suffer from focal and segmental glomeruloesclerosis.

Further investigations are indicated if the cause is not clear including analysis of auto-immune markers (ANA, ASOT, C3, cryoglobulins, serum electrophoresis), or ultrasound of the whole abdomen.

A broad classification of nephrotic syndrome based on underlying cause:

Nephrotic syndrome is often classified histologically:

Glomerulonephrosis is a non-inflammatory disease of the kidney (nephrosis) presenting primarily in the glomerulus (a glomerulopathy).

It can be contrasted to glomerulonephritis, which implies inflammation.

It can be caused by diethylnitrosamine.