Nephrology: Nephrotic syndrome Flashcards
What causes nephrotic syndrome?
Increased permeability of serum protein through a damaged basement membrane in the renal glomerulus
What are the clinical features of nephrotic syndrome?
1) Proteinuria >3-3/5g/day
2) Oedema
3) Hypoalbuminaemia
4) Hyperlipidaemia
5) Lipiduria
What is the pathophysiology of nephrotic syndrome?
1) Cytokines damage podocytes causing them to fuse together and destroy charge of the GBM
2) This allows increased permeability to plasma proteins which causes massive protein loss in the urine
3) As a result of this, serum albumin levels are reduced beyond the synthetic ability of the liver
4) Thus patients experience marked oedema as with less albumin in the blood stream, there is less oncotic pressure
5) This lets fluid leak out into the interstitium
6) As an attempt to maintain oncotic pressure, the liver tries to compensate by increased synthesis of lipoproteins - this is one of the mechanisms postulated to cause the hyperlipidaemia
However, the full mechanism is not fully understood.
What is the most common cause of nephrotic syndrome in adults?
Membranous glomerulonephritis
What is the most common cause of nephrotic syndrome in children?
Minimal change disease
What are causes of nephrotic syndrome?
1) Systemic disease
2) Minimal change disease/glomerulonephritis
3) Membranous nephropathy (40% have spontaneous remission)
4) Focal segmental glomerulosclerosis
5) Membranoproliferative/mesangiocapillary glomerulonephritis (less common)
What are systemic disease causes of nephrotic syndrome?
1) Diabetes - glomerulosclerosis
2) SLE - membranous
3) Amyloidosis
What condition is minimal change disease associated with?
URTI (1% go on to have end-stage renal failure)
What does minimal change disease look like on biopsy?
Normal light microscopy
Electron microscope: fusion of podocyte foot processes and effacement of podocyte foot processes
How do you treat minimal change disease?
Steroids
What is membranous nephropathy associated with?
1) Cancers - lung, colon, breast
2) Autoimmune - SLE, thyroid disease
3) Infections - Hep B
4) Drugs - penicillamine and gold
What does membranous nephropathy look like on biopsy?
Subepithelial immune complex deposits (thickening of the basement membrane)
What is focal segmental glomerulosclerosis associated with?
1) More common in Afro-Caribbean population
2) Associated with IgA nephropathy, sickle cell disease, HIV
What does focal segmental glomerulosclerosis look like on biopsy?
Focal scarring (sclerotic lesions involving < 50% of glomeruli), IgM antibody deposition
How do you treat focal segmental glomerulosclerosis?
Steroids or cyclophosphamide/ciclosporin
What % of patients with focal segmental glomerulosclerosis progress to end stage renal failure?
30-50%
What % of patients with membranoproliferative/mesangiocapillary glomerulonephritis progress to end stage renal failure?
50%
How does membranoproliferative/mesangiocapillary glomerulonephritis present?
Both nephrotic and nephritic syndrome
What is membranoproliferative/mesangiocapillary glomerulonephritis associated with?
Hepatitis B, hepatitis C and endocarditis
How does nephrotic syndrome present?
1) Periorbital/facial and peripheral oedema (non-dependent oedema)
2) Frothy urine - proteinuria
What investigations should be done in nephrotic syndrome and what do they show?
1) Urine dipstick - proteinuria
2) Urine analysis - raised albumin:creatinine ratio
When is renal biopsy indicated for nephrotic syndrome?
1) All adults - essential to identify the underlying histological cause
2) Children with an atypical presentation e.g. steroid unresponsive, haematuria, < 1 years old or > 12 years old
What is the management for nephrotic syndrome?
High dose oral steroids which should be tapered according to clinical response
What are complications of nephrotic syndrome?
1) Infection - due to urinary loss of immunoglobulins
2) VTE - due to urinary loss of antithrombin III
3) Hyperlipidaemia - due to increased hepatic production of lipids to restore the serum oncotic pressure
