Aetiology
Nephrotic syndrome may be caused by primary glomerular disorders (80–90% of cases) and/or systemic diseases and toxic exposures (10–20% of cases)
Primary causes
- Minimal change disease
- Focal segmental glomerulosclerosis
- Membranous nephropathy
Secondary forms
- Diabetic nephropathy
- Amyloid nephropathy -> an be associated with multiple myeloma (AL amyloidosis) or chronic inflammatory disease such as rheumatoid arthritis (AA amyloidosis)
Selective proteinuria--> Can be found in diseases with mild damage to the glomeruli
- Minimal change disease--> cytokine-mediated damage of podocytes--> loss of negative charge of the foot processes--> Only small- to medium-sized proteins can be found in the urine (primarily albumin)--> selective proteinuria
All other nephrotic syndromes will cause non selective proteinuria
- Focal segmental glomerulosclerosis:
o sclerosis (scarring) of glomeruli → effacement of the podocyte foot processes. The trigger for this is not known
- Membranous neuropathy
o There is the formation immune complexes that deposit in the glomeruli basement membrane--> activate the complement system, leading to podocyte injury.
- Amyloid nephropathy
o Amyloid deposition in glomeruli → mesangial expansion → nodular sclerosis
- Diabetic
o Chronic hyperglycaemia → glycation of the basement membrane → increased permeability and thickening of the basement membrane and stiffening of the efferent arteriole → hyperfiltration (increase in GFR) → increase in intraglomerular pressure → progressive glomerular hypertrophy, increase in renal size, and glomerular scarring (glomerulosclerosis) → worsening of filtration capacity
- Lupus nephritis
o Mesangial and/or subendothelial deposition of immune complexes (e.g., anti-dsDNA antibodies, anti-Sm antibodies) → expansion and thickening of mesangium, capillary walls, and/or glomerular basement membrane
o Note: Can manifest as nephritic syndrome and/or nephrotic syndrome