GLOMERULAR DISEASE COPY COPY Flashcards by Alex Kinsky

What are the two main defining findings of glomerular disease?

Proteinuria

Haematuria

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What part of the glomerulus is damaged if there is haematuria (and small amounts of proteinuria)?

Capillary endothelial cell lining

Endothelial side of the glomerular basement membrane

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What part of the glomerulus is damaged if there is proteinuria (but not haematuria)?

Podocytes

Podocyte side of the glomerular basement membrane

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When thinking about glomerular disease what are the three different elements to consider?

Syndrome - presenting condition
Histological pattern - biopsy picture
Disease cause

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What are the three presenting syndromes associated with glomerular disease?

Nephrotic syndrome

Nephritic syndrome

Mixed nephritic/nephrotic picture

(Asymptomatic proteinuria/haematuria)

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What do we mean by asymptomatc proteinuria/haematuria?

Where there are no other features of the protein or blood loss such as those seen in nephrotic or nephritis syndromes.

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What are the main features of nephrotic syndrome?

Protein loss of more than 3.5g per day. This leads to the clinical picture:

Hypoalbuminaemia (serum albumin typically less than 25g/L)

Oedema

Hyperlipidaemia/Hypercholesteraemia

(Hypercoagulability - not alway considered a mainstay of nephrotic syndrome)

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Why do people with nephrotic syndrome get oedema?

Hypoalbuminaemia leads to a loss of oncotic pressure which means water is pulled out into the tissues.
The resulting hypovolaemia leads to stimulation of the renin-angiotensin system which leads to retention of more water.

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Why do people with nephrotic syndrome develop hyperlipidaemia?

The lack of protein the blood stimulates the liver to produce more protein, resulting in the overproduction of lipoproteins.

There is also a loss of lipoprotein lipase from the kidneys so lipid breakdown is reduced.

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Why do people with nephrotic syndrome develop hypercoagulability?

This is mainly due to a relatively big loss of antithrombin III.

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What are the other less common features of nephrotic syndrome, other than protein loss, hypoalbuminaemia, hyperlipidaemia, oedema and hypercoagulability?

Hypertension - can also be a cause

Anaemia due to loss of transferrin

Dyspnea - due to pulmonary oedema

Lipiduria - fat globules can also make their way through the glomerulus

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How we treat all patients currently suffering nephrotic syndrome regardless of the cause or histological pattern?

Blood pressure control

ACE inhibitors reduce proteinuria

Control hyperlipidaemia

Anticoagulate as increased risk of thrombosis with loss of clotting factors

Treat underlying cause

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What are the three main structures of the glomerulus that can be damaged to cause disease?

Capillary endothelial cell lining
(Mesangium supporting the capillaries)

Glomerular basement membrane

Podocytes on the outer surface of the glomerulus

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What are the histological patterns associated with nephrotic syndrome?

Minimal change nephropathy

Membranous glomerulonephritis

Focal segmental glomerulosclerosis

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What is the histological pattern of minimal change disease?

Damage to the podocytes only seen on electron microscopy

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What is the histological pattern of membranous glomerulonephropathy?

Widespread glomerular basement thickening

Subepithelial deposition of immune complexes

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What is the histological pattern of focal segmental glomerulosclerosis?

Podocyte foot process fusion or fibrosis, with hyaline deposits in the glomerular segments.

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What are the causes of nephrotic syndrome with a minimal change nephropathy histological pattern?

Idiopathic minimal change disease

Possibly NSAID related

Diabetes can produce the same picture

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Who tends to be affected by idiopathic minimal change disease of the glomerulus?

Most common (90%) cause of nephrotic syndrome in children often following an upper respiratory tract infection.

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What are the non-renal disorders associated with idiopathic minimal change disease of the glomerulus?

Asthma

Eczema

Hay fever

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How is idiopathic minimal change disease of the glomerulus treated?

Corticosteroids and ciclosporin

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What are the causes of nephrotic syndrome with a membranous glomerulonephritis histological pattern?

Idiopathic membranous glomerulonephropathy

Infections: syphilis, malaria, hepatitis B

Tumours: melanoma, carcinoma of the bronchus, lymphoma

Drugs: penicillamine, heroin, mercury, gold

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What are the infections which can cause nephrotic syndrome with a membranous glomerulonephritis histological pattern?

Syphilis

Malaria

Hepatitis B

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What are the tumours which can cause nephrotic syndrome with a membranous glomerulonephritis histological pattern?

Melanoma

Carcinoma of the bronchus

Lymphoma

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What are the drugs which can cause nephrotic syndrome with a membranous nephropathy histological pattern?

Penicillamine Heroin Mercury Gold

How is nephrotic syndrome with a membranous glomerulonephritisc histological pattern treated?

Corticosteroids Ciclosporin Cyclophosphamide Chlorambucil Treat underlying cause if secondary 1/3 resolve, 1/3 respond to cytotoxics, 1/3 develop chronic kidney disease

What are the causes of nephrotic syndrome with a focal segmental glomerulosclerotic histological pattern?

Idiopathic focal segmental glomerulosclerosis AIDS Heroin use Amyloidosis

How is nephrotic syndrome with a focal segmental glomerulosclerotic histological pattern treated?

Steroids, cyclophosphamide, ciclosporin, dialysis and renal transplant. Recurrence does happen in transplanted patients.

What proportion of cases of nephrotic syndrome does the focal segmental glomerulosclerotic pattern account for?

Up to 15-30% of adults 10% of children

Does a focal segmental glomerulosclerotic histological pattern always present with the features of nephrotic syndrome?

No. It can progress to haematuria as well.

What is the most common histological pattern associated with nephrotic syndrome in children?

Minimal change glomerulonephropathy

What is the most common histological pattern associated with nephrotic syndrome in adults?

Membranous glomerulonephropathy

What are the main features of nephritic syndrome?

Haematuria Proteinuria (but less than the 3.5g per day seen in nephrotic syndrome) Hypertension Uraemia Renal insufficiency (AKI) Malaise

What is seen in the urinalysis of someone with nephritis syndrome?

Red cell casts

What are the main histological categories associated with a pure nephritic syndrome?

Rapidly progressive glomerulonephritis IgA nephropathy

What is rapidly progressive (crescentic) glomerulonephritis?

Leakage of fibrin from injured glomerular cells stimulates epithelial cells and macrophages within Bowman's capsule to proliferate and form crescent shaped masses, reducing glomerular blood supply.

What are the causes of rapidly progressive (crescentic) glomerulonephritis?

Idiopathic Vasculitis - microscopic polyarteritis nodosa, Wegener's granulomatosis Goodpasture's disease

How does Goodpasture's syndrome cause glomerular damage?

Autoantibodies to type IV collagen in the basement membrane cause inflammation.

What type of glomerular damage (histological diagnosis) is seen in patients with Goodpasture's syndrome?

Rapidly progressive 'crescentic' glomerulonephritis

How is Goodpasture's syndrome treated?

Plasma exchange Corticosteroids

What is microscopic polyarteritis nodosa (microscopic polyangitis)?

A necrotizing vasculitis affecting the small arteries of the body.

Is microscopic polyarteritis nodosa (microscopic polyangitis) more common in males or females?

Males

What is the antibody associated with microscopic polyarteritis nodosa (microscopic polyangitis)?

Antineutrophil cytoplasmic antibodies (ANCA)

What is Wegener's granulomatosis?

A rare necrotizing vasculitis, similar to microscopic polyarteritis nodosa, with granuloma formation.

What are the organs affected by Wegener's granulomatosis?

Nose Upper respiratory tract Kidneys

How does Wegener's granulomatosis affect the nose?

Saddle nose deformity

What is the antigen-antibody complex associated with microscopic polyarteritis nodosa?

pANCA - MPO

What is the antigen-antibody complex associated with Wegener's granulomatosis?

cANCA - PR3

How do you treat rapidly progressive (crescentic) glomerulonephritis?

Immunosuppressants - steroids Treat underlying cause if secondary

What is IgA nephropathy also called?

Berger's disease

What are the histological features IgA nephropathy (Berger's disease)?

Mesangial cell proliferation IgA and C3 deposition in the measangium

Who is affected by IgA nephropathy?

Typically affects young men after a upper respiratory tract infection.

How do you treat IgA nephropathy (Berger's disease)?

There is no effective treatment. 20-30% will develop end-stage renal failure.

What are the conditions associated with IgA nephropathy?

Henoch-Schonlein purpura - very similar picture to IgA nephropathy Alcoholic cirrhosis Coeliac disease/dermatitis herpetiformis Alport's syndrome

What is Henoch-Schonlein purpura (HSP)?

An immune mediated systemic vasculitis that affects many parts of the body including skin, joints, gut, and kidney. HSP can follow an upper respiratory tract infection.

Which group of patients is Henoch-Schonlein purpura (HSP) most likely to affect?

Male children

How does Henoch-Schonlein purpura (HSP) differ histologically from IgA nephropathy (Berger's disease)?

It doesn't really

What are the skin changes associated with Henoch-Schonlein purpura (HSP)?

Purpuric rash seen over the extensor surfaces of the legs, arms and buttocks

What are the intestinal changes associated with Henoch-Schonlein purpura (HSP)?

Abdominal pain, vomiting and bleeding

What is the treatment for Henoch-Schonlein purpura (HSP)?

Children usually recover without need for treatment

What is Alport's syndrome and what are the features?

X-linked disease characterised by an abnormality of the basement membrane collagen. Patients present with glomerulonephritis and haematuria, ocular abnormalities (including cataracts) and sensorineural deafness. Associated with platelet dysfunction and hyperproteinaemia.

What do patients who are carriers of Alport's syndrome have and what are the symptoms?

Thin membrane disease Uncomplicated haematuria

What are the main histological categories associated with a mixed nephritic/nephrotic presentation?

Diffuse proliferative glomerulonephritis Membranoproliferative glomerulonephritis (mesangiocapillary)

What is the histological pattern of diffuse proliferative glomerulonephritis?

Endothelial and mesangial cell proliferation Glomerular infiltration by neutrophils and monocytes Deposition of immune complexes (antibody, antigen and complement)

What are the causes of mixed nephritic/nephrotic syndrome with a diffuse proliferative glomerulonephritic histological pattern?

Infection - classic post-streptococcal. Also infective endocarditis, toxoplasmosis, malaria, some viruses SLE Thrombotic microangiopathies

What is the infection that most commonly causes a mixed nephritic/nephrotic syndrome?

Group A beta-haemolytic streptococcal infection of the tonsils, pharynx or skin. Strep pyogenes. Presentation is mostly nephritic

Group A beta-haemolytic streptococcal infection of the tonsils, pharynx or skin. Strep pyogenes.

1-3 weeks

How is post-streptococcal glomerulonephritis treated?

Conservative management with antibiotics

What is the prognosis for someone treated for post-streptococcal glomerulonephritis?

Children tend to recover fully but only 60% of adults recover without hypertension or renal impairment.

What are the thrombotic microangiopathies associated with diffuse proliferative glomerulonephritis?

Hemolytic uremic syndrome Thrombotic thrombocytopenic purpura

What are the causes of mixed nephritic/nephrotic syndrome with a membranoproliferative glomerulonephritic (mesangiocapillary) histological pattern?

Type 1: cryoglobulinaemia, hepatitis C Type 2: partial lipodystrophy

What type of histological patterns of glomerular disease is most commonly associated with SLE?

Diffuse proliferative glomerulonephritis

What types of histological patterns of glomerular disease are associated with SLE?

Diffuse proliferative glomerulonephritis - most common Membranous glomerulonephropathy Rapidly progressive (crescentic) glomerulonephritis

What are the glomerular changes seen in SLE?

Immune complex deposition in glomerulus (all classes of Ig) Basement membrane thickening Endothelial proliferation

How does diabetes affect the glomerulus?

Nodular glomerulosclerosis (Kimmelstiel-Wilson syndrome) Thickening of capillary basement membrane Increase in matrix of the mesangium This leads to loss of protein by normally not a full blown nephrotic syndrome, unless the biopsy shows the same features as minimal change disease.

How does multiple myeloma affect the glomerulus?

Cause light chain deposition disease and amyloidosis which produces loss of protein and a similar picture to nephrotic syndrome. This is not the same as myeloma kidney which is a tubular defect.

GLOMERULAR DISEASE COPY COPY Flashcards

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