Idiopathic nephrotic syndrome
The term idiopathic nephrotic syndrome is used for a collection of diseases that cause nephrotic syndrome, that are not secondary (i.e. not systemic, infectious, related to medications, or hereditary). We have listed the main idiopathic nephrotic diseases below:
- Minimal change disease (5-10%)
- Focal segmental glomerulosclerosis (20-25%)
- Membranous nephropathy (25-30%)
- Membranoproliferative glomerulonephritis (5%)
- Other proliferative and sclerosing glomerulonephritides (15-30%)
In this question, we’ll focus only on the first two, minimal change and focal segmental, as Membranous and Membranoproliferative are covered below.
Minimal change disease
This is the most common nephrotic disease in children, although only a small percentage in adults. Presentation is that of weight gain, with periorbital and peripheral edema due to protein loss from proteinuria. Hypertension and hematuria are not always present, but often (30%). Complement and serological test levels remain normal.
There is no histopathological difference in the glomeruli under light microscopy (hence minimal change). Tubules may show lipid droplet accumulation, but there are no immune-type deposits. By electron microscopy we can identify effacement of the visceral epithelial podocytes along the whole of the capillary loop. It is thought that this effacement is a result of T-cell cytokine release which damages the podocytes.
Image: “Minimal Change Disease Pathology Diagram” by Renal_corpuscle.svg: M • Komorniczak -talk- (polish Wikipedist) derivative work: Huckfinne ( talk ), CC BY-SA 3.0, via Wikimedia Commons.
Minimal change disease is idiopathic, although commonly associated with Hodgkin's lymphoma.
Treatment of corticosteroids is highly effective in children (cyclophosphamide or ciclosporin), use diuretics with care to avoid hyponatremia, restrict fluid intake while patient is oedematous.
Focal segmental glomerulosclerosis
FSG can be primary and idiopathic, or secondary as a result of heroin abuse, HIV, sickle cell disease, obesity, urine reflux and nephrotic lesions.
The idiopathic, primary, form owes mainly to a circulating permeability factor; genetic forms owe to a defect in components of the podocyte, passed down in AD fashion (mutation to alpha-actinin 4). This genetic defect means a failure of the podocytes to stop some plasma proteins and lipids. This goes on to cause a build up of lipids and proteins in the bowman's capsule causing hyalinosis, overtime these areas go on to become sclerotic.
Clinical manifestation is asymptomatic proteinuria or edema, with hypertension common and microscopic hematuria also in about half of patients along with decreased eGFR in about 30% of patients.