Nephrology: Nephrotic syndrome

Question 1

What causes nephrotic syndrome?

Answer 1

Increased permeability of serum protein through a damaged basement membrane in the renal glomerulus

Question 2

What are the clinical features of nephrotic syndrome?

Answer 2

1) Proteinuria >3-3/5g/day
2) Oedema
3) Hypoalbuminaemia
4) Hyperlipidaemia
5) Lipiduria

Question 3

What is the pathophysiology of nephrotic syndrome?

Answer 3

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.

Question 4

What is the most common cause of nephrotic syndrome in adults?

Answer 4

Membranous glomerulonephritis

Question 5

What is the most common cause of nephrotic syndrome in children?

Answer 5

Minimal change disease

Question 6

What are causes of nephrotic syndrome?

Answer 6

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)

Question 7

What are systemic disease causes of nephrotic syndrome?

Answer 7

1) Diabetes - glomerulosclerosis
2) SLE - membranous
3) Amyloidosis

Question 8

What condition is minimal change disease associated with?

Answer 8

URTI (1% go on to have end-stage renal failure)

Question 9

What does minimal change disease look like on biopsy?

Answer 9

Normal light microscopy
Electron microscope: fusion of podocyte foot processes and effacement of podocyte foot processes

Question 10

How do you treat minimal change disease?

Answer 10

Steroids

Question 11

What is membranous nephropathy associated with?

Answer 11

1) Cancers - lung, colon, breast
2) Autoimmune - SLE, thyroid disease
3) Infections - Hep B
4) Drugs - penicillamine and gold

Question 12

What does membranous nephropathy look like on biopsy?

Answer 12

Subepithelial immune complex deposits (thickening of the basement membrane)

Question 13

What is focal segmental glomerulosclerosis associated with?

Answer 13

1) More common in Afro-Caribbean population
2) Associated with IgA nephropathy, sickle cell disease, HIV

Question 14

What does focal segmental glomerulosclerosis look like on biopsy?

Answer 14

Focal scarring (sclerotic lesions involving < 50% of glomeruli), IgM antibody deposition

Question 15

How do you treat focal segmental glomerulosclerosis?

Answer 15

Steroids or cyclophosphamide/ciclosporin

Question 16

What % of patients with focal segmental glomerulosclerosis progress to end stage renal failure?

Answer 16

30-50%

Question 17

What % of patients with membranoproliferative/mesangiocapillary glomerulonephritis progress to end stage renal failure?

Answer 17

50%

Question 18

How does membranoproliferative/mesangiocapillary glomerulonephritis present?

Answer 18

Both nephrotic and nephritic syndrome

Question 19

What is membranoproliferative/mesangiocapillary glomerulonephritis associated with?

Answer 19

Hepatitis B, hepatitis C and endocarditis

Question 20

How does nephrotic syndrome present?

Answer 20

1) Periorbital/facial and peripheral oedema (non-dependent oedema)
2) Frothy urine - proteinuria

Question 21

What investigations should be done in nephrotic syndrome and what do they show?

Answer 21

1) Urine dipstick - proteinuria
2) Urine analysis - raised albumin:creatinine ratio

Question 22

When is renal biopsy indicated for nephrotic syndrome?

Answer 22

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

Question 23

What is the management for nephrotic syndrome?

Answer 23

High dose oral steroids which should be tapered according to clinical response

Question 24

What are complications of nephrotic syndrome?

Answer 24

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

Question 25

Which condition is a significant risk factor for the development of nephrotic syndrome?

Answer 25

Diabetes

Question 26

What causes the non-dependent oedema in nephrotic syndrome?

Answer 26

1) Podocytes which prevent protein excretion into the glomerular filtrate are disrupted, resulting in the loss of small proteins such as albumin
2) This in turn leads to a reduction of intravascular oncotic pressure and the extravasation of water into the interstitium

Question 27

What respiratory condition does nephrotic syndrome predispose to bc of the non-dependent oedema?

Answer 27

Pleural effusions - acute dyspnoea, reduced air entry at both lung bases with dullness to percussion

Question 28

How would you use furosemide in nephrotic syndrome?

Answer 28

1) Furosemide is a high ceiling loop diuretic often used as an adjunct to manage fluid overload states in nephrotic syndrome
2) If pleural effusions are found, Furosemide can then be administered as a next step, usually IV if quick resolution is preferred
3) Furthermore, patients with nephrotic syndrome are often intravascularly dehydrated and the presumptive administration of a diuretic may cause further volume depletion

Question 29

Which blood gas may be useful in nephrotic syndrome?

Answer 29

Venous blood gas - to review evidence of acidosis or high lactate

Question 30

What treatment can be given in nephrotic syndrome with specialist input?

Answer 30

Infusion of human albumin solution - to elevate intravascular oncotic pressure

Question 31

What is the first line investigation for pleural effusion?

Answer 31

CXR - would help with evaluating the presence and size of any pleural effusions and other respiratory differentials for acute shortness of breath

Question 32

Which condition presents as a pure nephrotic syndrome?

Answer 32

Minimal change disease

Question 33

Which two conditions present as a nephrotic syndrome with some haematuria?

Answer 33

1) Membranous nephropathy
2) Focal segmental glomerulonephritis

Question 34

Which condition presents as a nephritic syndrome with nephrotic range proteinuria?

Answer 34

Membranoproliferative (mesangiocapillary) glomerulonephritis

Question 35

What does proliferative glomerulonephritis look like on renal biopsy?

Answer 35

Epithelial cellular proliferation