Nephrotic Syndrome

Question 1

… syndrome is broadly defined as a triad of heavy proteinuria > 3.5 g/day, hypoalbuminaemia, and oedema.

Answer 1

Nephrotic syndrome is broadly defined as a triad of heavy proteinuria > 3.5 g/day, hypoalbuminaemia, and oedema.

Question 2

The cause of nephrotic syndrome may be broadly divided into … or ….

Answer 2

The cause of nephrotic syndrome may be broadly divided into primary or secondary.

Question 3

Primary - nephrotic syndrome

Answer 3

Due to a primary renal glomeruli injury

Minimal change disease
Focal segmental glomerulosclerosis
Membranous nephropathy

Question 4

Secondary - nephrotic syndrome

Answer 4

Glomerular injury due to a wider systemic illness

Diabetes mellitus
Amyloidosis
Human immunodeficiency virus

Question 5

Patients with nephrotic syndrome typically present with features of …

Answer 5

Patients with nephrotic syndrome typically present with features of fluid overload.

Question 6

Symptoms of nephrotic syndrome: (6)

Answer 6

Fatigue
Poor appetite
Peripheral oedema
Periorbital oedema
Shortness of breath: typically from pleural effusions and/or pulmonary oedema
Foamy urine: due to excess protein loss

Question 7

Signs of nephrotic syndrome:

Answer 7

The salient feature is the presence of fluid overload.

Oedema: peripheral, periorbital
Ascites: fluid in the peritoneal cavity
Effusions: dull percussion note and reduced air entry

Question 8

The diagnosis of nephrotic syndrome is based on the identification of the typical triad - what is this?

Answer 8

‘Nephrotic-range’ proteinuria (> 3.5 g/day)
Hypoalbuminaemia (< 35 g/L)
Oedema (e.g. peripheral, periorbital)

Question 9

The management of nephrotic syndrome depends on …

Answer 9

The management of nephrotic syndrome depends on the underlying cause.

Question 10

Patients with nephrotic syndrome are at risk of both … and … complications

Answer 10

Patients with nephrotic syndrome are at risk of both arterial and venous thrombotic complications.

Question 11

Thrombotic complications - nephrotic syndrome

Answer 11

Bloods clots are observed in 10-40% of patients with nephrotic syndrome. This can occur in both the arterial and venous system, but Deep venous thrombosis and Pulmonary embolism (PE) are particularly common. Patients should be assessed for leg swelling and features of PE (chest pain, shortness of breath).

Question 12

Hyperlipidaemia - nephrotic syndrome

Answer 12

A variety of lipid abnormalities may occur in nephrotic syndrome, which can include hypercholesterolaemia and hypertriglyceridaemia. A fall in oncotic pressure increases the rate of lipoprotein synthesis in the liver that results in a high level of cholesterol. In addition, impaired metabolism of triglycerides is thought to occur due to reduced activity of lipoprotein lipase (this enyzme breaks down very-low-density lipoproteins and intermediate-density lipoproteins) due to loss of circulating activating factors.

Question 13

Patients are at increased risk of infections in nephrotic syndrome - why?

Answer 13

Patients are at increased risk of infections, particularly encapsulated bacteria, due to loss of immunoglobulins through the glomeruli.

Question 14

Acute kidney injury - does it happen in nephrotic syndrome?

Answer 14

Renal impairment may be seen in nephrotic syndrome due to a variety of complex mechanisms but it is less common compared to glomerulonephritis (i.e. causes of nephritic syndrome).

Question 15

… … disease accounts for the majority of cases of nephrotic syndrome in young children.

Answer 15

Minimal change disease accounts for the majority of cases of nephrotic syndrome in young children.

Question 16

Minimal change disease is considered the most common cause nephrotic syndrome in who?

Answer 16

Minimal change disease is considered the most common cause nephrotic syndrome in children. In children under the age of 10 years old, it accounts for ~90% of cases. In adults, it accounts for a much smaller proportion (~10%) of nephrotic syndrome.

Question 17

The majority of cases of minimal change disease are idiopathic (primary). However, some cases are associated with a distinct underlying cause (secondary). These include:

Answer 17

Drugs (e.g. NSAIDs)
Malignancy (e.g. lymphoproliferative disorders)
Infections (e.g. syphilis - rarely)

Question 18

In …, minimal change disease is usually a presumptive diagnosis in the presence of nephrotic syndrome because of how common the condition is in this age group. Treatment can be initiated and response assessed.

Answer 18

In children, minimal change disease is usually a presumptive diagnosis in the presence of nephrotic syndrome because of how common the condition is in this age group. Treatment can be initiated and response assessed.

Question 19

In adults, the diagnosis of nephrotic syndrome is harder to make and usually involves renal … to investigate the cause of nephrotic syndrome.

Answer 19

In adults, the diagnosis is harder to make and usually involves renal biopsy to investigate the cause of nephrotic syndrome.

Question 20

The principal treatment of minimal change disease is systemic … (e.g. …). This will often lead to complete remission. In patients who do not respond, further courses of … or more intensive immunosuppressive can be used.

Answer 20

The principal treatment of minimal change disease is systemic glucocorticoids (e.g. prednisolone). This will often lead to complete remission. In patients who do not respond, further courses of prednisolone or more intensive immunosuppressive can be used.

Question 21

Focal segmental … describes a histological lesion seen in some cases of nephrotic syndrome.

Answer 21

Focal segmental glomerulosclerosis describes a histological lesion seen in some cases of nephrotic syndrome.

Question 22

…. (FSGS) is a histological term that refers to sclerosis in parts of at least one glomerulus. It is broadly classified as primary, secondary, or genetic. It is a common cause of nephrotic syndrome, especially adults.

Answer 22

Focal segmental glomerulosclerosis (FSGS) is a histological term that refers to sclerosis in parts of at least one glomerulus. It is broadly classified as primary, secondary, or genetic. It is a common cause of nephrotic syndrome, especially adults.

Question 23

FSGS is a … diagnosis made on renal …. There are a number of histological variants that may be present. The presentation of FSGS in childhood suggests an underlying genetic cause.

Answer 23

FSGS is a histological diagnosis made on renal biopsy. There are a number of histological variants that may be present. The presentation of FSGS in childhood suggests an underlying genetic cause.

Question 24

Management of FSGS:

It is crucial to differentiate between primary and secondary causes of FSGS because the treatment differs between groups. Primary FSGS is more akin to minimal change disease and is treated with … medications. Treatment of secondary FSGS should be targeted towards the suspected underlying cause (e.g. weight loss of obesity).

Answer 24

It is crucial to differentiate between primary and secondary causes of FSGS because the treatment differs between groups. Primary FSGS is more akin to minimal change disease and is treated with immunosuppressive medications. Treatment of secondary FSGS should be targeted towards the suspected underlying cause (e.g. weight loss of obesity).

Question 25

Membranous … is one of the most common causes of nephrotic syndrome in adults.

Answer 25

Membranous nephropathy is one of the most common causes of nephrotic syndrome in adults.

Question 26

Membranous nephropathy (MN) is characterised by glomerular … membrane … in the absence of significant cellular proliferation on histology. It is a common cause of nephrotic syndrome in adults and may be primary or secondary.

Answer 26

Membranous nephropathy (MN) is characterised by glomerular basement membrane thickening in the absence of significant cellular proliferation on histology. It is a common cause of nephrotic syndrome in adults and may be primary or secondary.

Question 27

Primary membranous nephropathy (MN) - why does it occur?

Answer 27

Primary MN is thought to occur due to an autoimmune reaction against important antigens in the filtration barrier. This leads to the development of autoantibodies, formation of immune deposits and subsequent thickening of the glomerular basement membrane. Antibodies directed against the phospholipase A2 receptor (PLA2R) that are highly expressed on podocytes are a major cause of primary MN seen in up to 80% of cases. Rarer antigen targets have been identified.

Question 28

Secondary membranous nephropathy occurs in the context of … (3)

Answer 28

Underlying infection, drug use, or a systemic disorder. Typical causes include systemic lupous erythematosus, viral hepatitis, prostate cancer, or even NSAID use.

Question 29

Traditionally, the diagnosis of MN requires histological analysis following renal biopsy. However, the presence of typical abnormal antibodies (e.g. anti-PLA2R) that are seen in primary MN enables a serological diagnosis in patients presenting with … syndrome.

Answer 29

Traditionally, the diagnosis of MN requires histological analysis following renal biopsy. However, the presence of typical abnormal antibodies (e.g. anti-PLA2R) that are seen in primary MN enables a serological diagnosis in patients presenting with nephrotic syndrome.

Question 30

The treatment of membranous nephropathy depends on the natural history of the condition as some patients may have spontaneous remission.

In patients at high risk of disease progression, who haven’t already developed irreversible renal damage, … agents may be used in primary MN. Treatment of secondary MN generally targets the underlying cause (e.g. removal of culprit drug).

Answer 30

The treatment of MN depends on the natural history of the condition as some patients may have spontaneous remission. In patients at high risk of disease progression, who haven’t already developed irreversible renal damage, immunosuppressive agents may be used in primary MN. Treatment of secondary MN generally targets the underlying cause (e.g. removal of culprit drug).

Question 31

… refers to the extracellular deposition of fibrils that contain a variety of proteins.

Answer 31

Amyloidosis refers to the extracellular deposition of fibrils that contain a variety of proteins.

Question 32

Renal amyloidosis is an important cause of … syndrome.

Answer 32

Renal amyloidosis is an important cause of nephrotic syndrome. There is excess deposition of amyloid fibrils in the glomerulus leading to nephrotic syndrome. It is commonly seen in two systemic forms of amyloidosis known as AL amyloidosis (excess light chains due to plasma cell disorders) and AA amyloidosis (excess precursor protein due to chronic inflammation).

Question 33

Renal amyloidosis is an important cause of nephrotic syndrome. There is excess deposition of amyloid fibrils in the glomerulus leading to nephrotic syndrome. It is commonly seen in two systemic forms of amyloidosis known as … amyloidosis (excess light chains due to plasma cell disorders) and … amyloidosis (excess precursor protein due to chronic inflammation).

Answer 33

Renal amyloidosis is an important cause of nephrotic syndrome. There is excess deposition of amyloid fibrils in the glomerulus leading to nephrotic syndrome. It is commonly seen in two systemic forms of amyloidosis known as AL amyloidosis (excess light chains due to plasma cell disorders) and AA amyloidosis (excess precursor protein due to chronic inflammation).

Question 34

Amyloid fibrils can contain a variety of … proteins. They are derived for … proteins (e.g. immunoglobulin light chains, amyloid precursors) that undergo conformational/structural changes for a variety of reasons. They subsequently form a beta-pleated sheet configuration that is resistant to degradation. Deposition in organs leads to disruption of normal tissue function and development of organ failure.

Answer 34

Amyloid fibrils can contain a variety of insoluble proteins. They are derived for soluble proteins (e.g. immunoglobulin light chains, amyloid precursors) that undergo conformational/structural changes for a variety of reasons. They subsequently form a beta-pleated sheet configuration that is resistant to degradation. Deposition in organs leads to disruption of normal tissue function and development of organ failure.

Question 35

The diagnosis of renal amyloid can be made on biopsy with identification of amyloid fibrils using … … staining (causes apple-green birefringence under polarised light). A diagnosis may be made by sampling tissue from another site due to the systemic nature of the condition (e.g. performing a ‘fat-pad’ biopsy from near the umbilicus).

Answer 35

The diagnosis of renal amyloid can be made on biopsy with identification of amyloid fibrils using Congo red staining (causes apple-green birefringence under polarised light). A diagnosis may be made by sampling tissue from another site due to the systemic nature of the condition (e.g. performing a ‘fat-pad’ biopsy from near the umbilicus).

Question 36

The diagnosis of renal amyloid can be made on biopsy with identification of amyloid fibrils using Congo red staining (causes apple-green … under polarised light). A diagnosis may be made by sampling tissue from another site due to the systemic nature of the condition (e.g. performing a ‘fat-pad’ biopsy from near the umbilicus).

Answer 36

The diagnosis of renal amyloid can be made on biopsy with identification of amyloid fibrils using Congo red staining (causes apple-green birefringence under polarised light). A diagnosis may be made by sampling tissue from another site due to the systemic nature of the condition (e.g. performing a ‘fat-pad’ biopsy from near the umbilicus).

Question 37

The diagnosis of renal amyloid can be made on biopsy with identification of amyloid fibrils using Congo red staining (causes …-… birefringence under … light). A diagnosis may be made by sampling tissue from another site due to the systemic nature of the condition (e.g. performing a ‘fat-pad’ biopsy from near the umbilicus).

Answer 37

The diagnosis of renal amyloid can be made on biopsy with identification of amyloid fibrils using Congo red staining (causes apple-green birefringence under polarised light). A diagnosis may be made by sampling tissue from another site due to the systemic nature of the condition (e.g. performing a ‘fat-pad’ biopsy from near the umbilicus).

Question 38

The treatment of amyloidosis depends on the underlying cause (e.g. AA amyloidosis, hereditary amyloidosis). In patients with renal involvement, … therapy is needed for managing nephrotic syndrome. In those with severe end-stage renal disease, … may be considered if appropriate.

Answer 38

The treatment of amyloidosis depends on the underlying cause (e.g. AA amyloidosis, hereditary amyloidosis). In patients with renal involvement, supportive therapy is needed for managing nephrotic syndrome. In those with severe end-stage renal disease, dialysis may be considered if appropriate.

Question 39

… syndrome occurs when the basement membrane in the glomerulus becomes highly permeable to protein, allowing proteins to leak from the blood into the urine. It is most common between the ages of 2 and 5 years. It presents with frothy urine, generalised oedema and pallor.

Answer 39

Nephrotic syndrome occurs when the basement membrane in the glomerulus becomes highly permeable to protein, allowing proteins to leak from the blood into the urine. It is most common between the ages of 2 and 5 years. It presents with frothy urine, generalised oedema and pallor.

Question 40

Management of minimal change disease is with …

Answer 40

Management of minimal change disease is with corticosteroids (i.e. prednisolone). The prognosis is good and most children make a full recovery, however it may reoccur.

Question 41

TIP: Minimal change disease comes up fairly frequently in exams as the most common cause of … syndrome in children. If you spot a 2 – 5 year old child with oedema, proteinuria and low albumin, you may be asked about the underling cause. The answer is likely to be … syndrome.

Answer 41

TOM TIP: Minimal change disease comes up fairly frequently in exams as the most common cause of nephrotic syndrome in children. If you spot a 2 – 5 year old child with oedema, proteinuria and low albumin, you may be asked about the underling cause. The answer is likely to be nephrotic syndrome.

Question 42

Nephritic VS Nephrotic Syndrome

Answer 42

Question 43

Nephritic syndrome overview

Answer 43

Nephritic syndrome is characterized by inflammation of the glomeruli (glomerulonephritis) and renal dysfunction. The most common cause is immunoglobulin A (IgA) nephropathy, also known as Berger’s disease, but other causes include postinfectious glomerulonephritis and lupus nephritis. Nephritic syndrome can present with oliguria, hypertension, and hematuria (cola-colored urine). Edema may also be present, although it is not nearly as severe as in nephrotic syndrome. Laboratory findings include hematuria, proteinuria (< 3.0 g/day), elevated BUN and creatinine, and red cell casts in urine.

Question 44

Nephrotic syndrome overview

Answer 44

Nephrotic syndrome develops as damage to glomeruli results in massive proteinuria and generalized edema (anasarca). It can be caused by a variety of disorders in adults (e.g., diabetes mellitus, amyloidosis, systemic lupus erythematosus (SLE), and focal segmental glomerulosclerosis). The most common cause in children is minimal change disease. The edema of nephrotic syndrome decreases the amount of intravascular fluid and decreases blood pressure, stimulating the kidneys to release renin. Ultimately, the adrenal glands respond by releasing aldosterone to retain sodium and water, which provides more fluid to contribute to the further development of edema. Laboratory findings include hypoalbuminemia, massive proteinuria (> 3.5 g/day), hyperlipidemia, and waxy casts and oval fat bodies in urine.