Nephrotic Syndrome: Focal Segmental Glomerulosclerosis

Question 1

Definition

Answer 1

Kidney disorder characterised by injury to the podocytes in the glomerulus, resulting in proteinuria. This can progress to nephrotic syndrome and, in some cases, end-stage renal disease.

Question 2

Epidemiology + Risk factors

Answer 2

Male
MC in adults
African-American and Hispanic
Family history: genes implicated include NPHS1, NPHS2, INF2

Question 3

Aetiology (VAMMOS)

Answer 3

Primary: Idiopathic
Secondary:
- Viral-associated: HIV, parvovirus B19
- Medications: Heroin, anabolic steroids, interferon-a
- Malignancy/haematological: Lymphoma, sickle cell disease
- Other renal conditions: Alport syndrome, contralateral kidney agenesis
- Systemic causes: HTN, Diabetes, Obesity

Question 4

Pathophysiology

Answer 4

Parts/Segments of the damaged/sclerosed glomerulus will allow protein to filter through into the urine
- ultimately people with FSGS develop nephrotic syndrome
Podocytes damaged same way as in nil disease
- not only that though, over time some of these proteins + lipids to get trapped + build up in the glomerulus = HYALINOSIS = where the tissue has a hyaline or glossy appearance on histology + its thought that over time these areas move onto develop sclerosis or scar tissue

Question 5

Signs

Answer 5

Oedema: due to hypoalbuminemia

Question 6

Symptoms

Answer 6

• Foamy urine: due to proteinuria
• Facial and peripheral oedema: swollen ankles are the commonest site
• Recurrent infections: due to hypogammaglobulinemia

Question 7

Investigations

Answer 7

Urine dipstick and MC&S: protein rule out UTI
Urine albumin to creatinine ratio (ACR): >30mg/mmol is severely increased, >70mg/mmol is strongly indicative of glomerulopathy (<3mg/mmol is normal)
Renal biopsy: for definitive diagnosis
PAS staining on light microscopy: focal (a portion of glomeruli) and segmental sclerosis
Electron microscopy: effacement of foot processes of podocytes (similar to minimal change disease)

Question 8

Treatment

Answer 8

Primary (idiopathic): Prednisolone
- Ciclosporin = offered in patients with contraindications
Secondary: Treat underlying conditions
General:
- ACE-inhibitor/ARB: offered to almost all patients with proteinuric chronic kidney disease to reduce the rate of disease progression
- Statin: all patients with nephrotic syndrome will be evaluated and treated for dyslipidaemia
- Oral warfarin: Consider warfarin in patients with a marked reduction in serum albumin and additional risks for thrombosis

Question 9

Complications

Answer 9

HTN
Infection susceptibility
Pro-thrombic state
Hyperlipidaemia
Hypothyroidism
Hypocalcaemia
AKI
CKD
Rapidly progressive glomerulonephritis