Proteinuria

Question 1

What are the three pathophysiological mechanisms which cause proteinuria?

Answer 1

• Glomerular
• Tubular
• Overflow

Question 2

What are the features of nephritic syndrome?

Answer 2

• Haematuria
• Oliguria
• Proteinuria <3g/24grs
• Fluid retention

Question 3

What are the features of nephrotic syndrome?

Answer 3

• Peripheral oedema
• Proteinuria >3g/24hrs
• Hypoalbuminaemia <25g/L
• Hypercholesterolaemia

Question 4

Name the 3 types of non-proliferative glomerulonephritis (associated with nephrotic syndrome)

Answer 4

• Minimal change disease
• Focal segmental glomerulosclerosis
• Membranous glomerulonephritis

Question 5

Name the 4 types of proliferative glomerulonephritis (associated with nephritic syndrome)

Answer 5

• IgA nephropathy
• Rapidly progressive glomerulonephritis (crescentic)
• Membranoproliferative (aka mesangiocapillary) glomerulonephritis
• Post infective glomerulonephritis

Question 6

Describe minimal change disease

Answer 6

Minimal change glomerulonephritis (also called minimal change disease) presents with nephrotic syndrome and accounts for 80% of all nephrotic syndrome in children and 20% of nephrotic syndrome in adults.​
The underlying cause of minimal change glomerulonephritis is unknown. The name minimal change glomerulonephritis comes from the lack of changes seen on light microscopy. ​

Question 7

What is the management for minimal change disease?

Answer 7

Supportive care: nutritional support, salt and fluid restriction​

Corticosteroids: first-line treatment in both adults and children (more data for efficacy in children) – usually prednisone​

Other immunosuppressants (e.g. calcineurin inhibitor, mycophenolate mofetil, rituximab): these are second-line management options, and their effectiveness is unclear

Question 8

Describe focal segmental glomerulosclerosis

Answer 8

Focal segmental glomerulosclerosis typically presents with nephrotic syndrome. It is the most common cause of nephrotic syndrome in adults. ​
It can be divided into primary FSGS (unknown cause with a possible genetic element) and secondary FSGS (caused by another disease process, e.g. HIV, lupus, reflux nephropathy).​
​
Investigations​:
Typical findings on renal biopsy are segmental scarring of some glomeruli and fusion of foot processes.

Question 9

What is the management of FSGS?

Answer 9

Lifestyle changes​

Supportive care: salt restriction diet and fluid management​

High-dose prednisolone: approximately 50% of patients respond and treatment can be up to four months in adults. Steroids to suppress the immune system.​

Blood pressure and cholesterol reducing medications.​
Cyclophosphamide or ciclosporin is used in some cases to reduce proteinuria​
In secondary FSGS treat the underlying cause.

Question 10

Describe membranous glomerulonephritis

Answer 10

Slowly progressive disease primarily affecting individuals between the ages of 30 – 50.​
Membranous glomerulonephritis is commonly idiopathic but can be associated with hepatitis B, malaria and systemic lupus erythematosus (SLE).​
Immune complex deposition results in complement activation against glomerular basement membrane proteins.​
​
Investigations - typical findings on renal biopsy include:​
Microscopic analysis: shows thickened glomerular basement membrane​
Immunofluorescence: shows diffuse uptake of IgG ​

Question 11

What is the management of membranous glomerulonephritis?

Answer 11

Supportive care: salt restriction and fluid management​

Corticosteroids are often used to treat progressive disease

Question 12

Describe IgA nephropathy

Answer 12

IgA nephropathy is also known as Berger’s disease. It is the most common form of glomerulonephritis in adults worldwide. IgA antibodies have an abnormal structure so they accumulate in the kidney. Develops during infection involving mucosal lining ie. GI or resp –> causes increase in IgA which builds up in the kidney (deposit in mesangial area). ​
IgA nephropathy typically presents as nephritic syndrome (macroscopic haematuria), 24-48 hours after an upper respiratory tract infection.​
​
Investigations - Kidney biopsy with immunofluorescence microscopy will show IgA deposition in the matrix.​

Increased numbers of mesangial cells​

Increased matrix (the cellular scaffolding that holds everything together)

Question 13

What is the treatment for IgA nephropathy

Answer 13

Once kidneys have been damaged they can’t be repaired. Treatment focused on preventing further damage and avoiding end-stage kidney disease.​
High-dose prednisolone or other immunosuppressive drugs: can reduce proteinuria and delay renal impairment​
ACE-inhibitors and ARBs to reduce blood pressure.

Question 14

Describe rapidly progressive glomerulonephritis (crescenteric)

Answer 14

Rapidly progressive glomerulonephritis (RPGN) is acute nephritic syndrome accompanied by microscopic glomerular crescent formation with progression to renal failure within weeks to months. RPGN is relatively uncommon, affecting 10 to 15% of patients with glomerulonephritis. It primarily occurs in patients aged 20 to 50 years. RPGN can be caused by anti-glomerular basement membrane antibody disease and vasculitic disorders (Granulomatosis with polyangiitis (GPA) or Microscopic polyangiitis)

Question 15

Describe membranoproliferative glomerulonephritis (MPGN)

Answer 15

Membranoproliferative glomerulonephritis is a group of immune-mediated disorders characterised histologically by glomerular basement membrane (GBM) thickening and proliferative changes on light microscopy. It should not be confused with membranous glomerulonephritis, a condition in which the basement membrane is thickened, but the mesangium is not.​
The disease is associated with hepatitis C and several autoimmune conditions including systemic lupus erythematosus (SLE).​
​
Investigations - Typical findings on renal biopsy include:​
Thickened basement membrane​
Thickened mesangium​
“Tram tracking” appearance​
Immunofluorescence shows subendothelial deposition of IgG.

Question 16

What is the management for membranoproliferazive glomerulonephritis?

Answer 16

Children (with nephrotic-range proteinuria): corticosteroids​

Adults: dipyridamole and aspirin​

Kidney transplantation for patients with end-stage renal disease

Question 17

Describe post-infective glomerulonephritis

Answer 17

Post-infectious glomerulonephritis (PIGN) is an immunologically mediated glomerular injury triggered by an infection. Most commonly associated with streptococcal infections (referred to as post-streptococcal glomerulonephritis). The disease typically presents approximately 2 weeks after infection with nephritic syndrome (i.e. gross haematuria, oliguria, oedema).​
​
Investigations - Typical findings on renal biopsy include:​
Diffuse proliferative and exudative glomerular histology​
Dominant C3 staining and subepithelial humps​
​
Diagnosis​
Symptoms and signs of glomerulonephritis​
History of recent infection (e.g. streptococcal)​
Raised streptococcal titres

Question 18

How does amyloidosis present and what is the treatment?

Answer 18

A rare disease that occurs when an abnormal protein, called amyloid, builds up in your organs and interferes with their normal function. Usually presents with unexplained weight loss, fatigue, and oedema resistant to diuretic therapy. Amyloid in the kidney can cause leakage of protein in the urine resulting in nephrotic syndrome.​

Treatment includes appropriate management of resulting clinical syndromes, such as nephrotic syndrome, neuropathy, cardiomyopathy, and conduction disorders.

Question 19

What are some other renal causes of proteinuria other than glomerulonephritis

Answer 19

Diabetes, amyloidosis, SLE and infection

Question 20

What are some non-renal causes of proteinuria

Answer 20

Fever, burns, severe hypertension, heart failure

Question 21

What are some transient causes of proteinuria?

Answer 21

Vigorous exercise, febrile illness, cold exposure

Question 22

Why do burns cause proteinuria?

Answer 22

Almost 2/3 of severe burns patients develop proteinuria. Proteinuria is associated with increased risk for AKI, ICU length of stay and mortality.​
Capillary Leak Syndrome - there is a systemic capillary leak after a large burn, which increases with burn size. A shift of intravascular fluid and proteins to the interstitial space.

Question 23

Why does severe hypertension cause proteinuria?

Answer 23

High BP constricts and narrows blood vessels in kidneys, reducing blood flow.

Question 24

Why does congestive heart failure cause proteinuria?

Answer 24

Endothelial dysfunction, inflammation​

When the heart is no longer pumping efficiently it becomes congested with blood, causing pressure to build up in the main vein connected to the kidneys and leading to congestion of blood in the kidneys, too. The kidneys also suffer from the reduced supply of oxygenated blood. ​
When the kidneys become impaired, RAAS system goes into overdrive in an attempt to increase blood supply to the kidneys. The heart then has to pump against higher pressure in the arteries, and eventually suffers from the increase in workload.

Question 25

Why does vigorous exercise cause proteinuria?

Answer 25

Increased plasma concentration of angiotensin II –> increases GFR to result in
filtration of protein through glomerular barrier

Exercise-induced proteinuria is of the mixed glomerular-tubular type and has been thought to be due to increased glomerular permeability to macromolecular proteins in response to activation of the renin-angiotensin system and catecholamines and a reduction in renal haemodynamics. ​

Strenuous exercise increases glomerular filtration of low-molecular-weight proteins (β2-microglobulin), which overwhelm the reabsorbing capacity of the tubular apparatus, causing temporary dysfunction and tubular proteinuria.

Question 26

Why does cold exposure cause proteinuria?

Answer 26

May be due to cold diuresis?​
Cold diuresis is the body’s way of preserving heat when it feels that you may be in danger of hypothermia. When your body begins to react to a drop in temperature, it starts to constrict your blood vessels to reduce blood flow to the skin and keep the warmth around your internal organs.​
This causes an increase in blood pressure because there is now the same amount of blood in your body being pumped through a smaller amount of space. In response to this increase in pressure, the kidneys begin to filter out excess fluid in the blood to reduce the blood’s volume, and therefore the pressure.