Nephrology

Question 1

Describe how nephrotic syndrome often presents.

Answer 1

As a triad/ tetrad or manifestations:

1) proteinuria (>3g/24 hours)
2) Hypoalbuminaemia
3) Oedema
4) Dyslipidaemia (specifically hypercholesterolaemia)

Question 2

Give a basic description of the pathophysiology in nephrotic syndrome.

Answer 2

Inflammation and damage to the glomerulus, specifically to podocytes. Damaged podocytes = protein loss.

Question 3

1) In nephrotic syndrome, why can there be an increased risk of infection.
2) What causes hypoalbuminaemia in nephrotic syndrome?
3) How can hypercholesterolaemia occur in nephrotic syndrome?

Answer 3

1) Because antibodies are proteins which can be lost in urine in nephrotic syndrome.
2) Loss of albumin from circulating blood.
3) Hypoalbuminaemia causes the liver to produce more proteins (albumin AND cholesterol).

Question 4

How does oedema occur in nephrotic syndrome?

Answer 4

Hypoalbuminaemia > reduced plasma oncotic pressure > water and electrolytes move into interstitium (less proteins = increased osmotic gradient) > oedema.

Question 5

In nephrotic syndrome, what causes decreased GFR?

Answer 5

Oedema > hypovolaemia > reduced venous return to the heart > less volume pumped to the body > decreased renal blood flow > decreased GFR.

** Inflammation already in the glomerulus contributes to decreased GFR.

Question 6

What is the consequence of decreased GFR in nephrotic syndrome?

Answer 6

Decreased GFR > renin released > RAAS unregulated > salt and water retention > increased BP > further oedema due to hypoproteinaemia.

Question 7

Give the 3 reasons as to why you would investigate nephrotic syndrome.

Answer 7

1) Assess severity.
2) To confirm the diagnosis
3) To differentiate between types and causes.

Question 8

List the investigations you would carry out in suspected nephrotic syndrome.

Answer 8

1) Urine dipstick
2) Urinalysis with microscopy
3) Bloods
4) Nephritis screen and serological studies
5) Radiology (USS) and renal biopsy

Question 9

In nephrotic syndrome why would you carry out a urine dipstick and urinalysis?

Answer 9

To look for protein, glucose, nitrites, leukocytes, BJPs and cellular casts.

Question 10

In nephrotic syndrome, which blood tests would you order?

Answer 10

FBC, U&Es. LFTS, creatinine, urea, CRP, glucose, lipid profile, ESR.

Question 11

What tests are involved in the nephritic screen and serological studies for nephrotic syndrome?

Answer 11

1) Autoimmune screen (ANA, dsDNA, ANCA, complement - C3/C4), anti-GBM antibodies).
2) Serum free light chains
3) Syphilis serology
4) Hep B, Hep C and HIV serology

Question 12

In a patient with nephrotic syndrome, what types of changes might you see on the biopsy with:

1) light microscopy
2) immunofluorescence
3) electron microscopy

Answer 12

1) General changes
2) Antibody/ immune complex stains
3) Detailed changes to the glomerulus.

Question 13

Describe steps for the general management of nephrotic syndrome.

Answer 13

1) Lifestyle advice
2) Treat the cause
3) Treat HTN and hypercholesterolaemia.
4) Fluid and salt restriction
5) Diuresis
6) ACEis/ ARBs
7) Prophylactic antigoaculation
8) Immunotherapy
9) Dialysis if severe

Question 14

For each manifestation below, name the associated signs and symptoms:

1) Dyslipidaemia
2) Hypoalbuminaemia
3) Oedema
4) Proteinaemia

Answer 14

1) Xanthalasma and xanthomata
2) Tiredness, leukonychia striata, oedema.
3) Peripheral oedema, pulmonary oedema, pleural effusion (these may cause breathlessness).
4) Frothy urine.

Question 15

Name 6 complications of nephrotic syndrome.

Answer 15

1) HTN
2) AKI
3) Infection
4) VTE
5) CKD
6) Hyperlipidaemia

Question 16

1) In nephrotic syndrome, what are 2 mechanisms of the injury to podocytes?
2) What could happen in the damaged area of the glomerular capsule also includes the glomerular basement membrane>

Answer 16

1) Immune complex deposition or complement protein activation.
2) Blood can also leak into the filtrate.

Question 17

Name the 4 primary causes of nephrotic syndrome.

Answer 17

1) Minimal change disease
2) Membranous glomerulonephritis
3) Focal segmental glomerulonephritis
4) Membranoproliferative glomerulonephritis

Question 18

Name 6 causes of secondary nephrotic syndrome.

Answer 18

1) Diabetic nephropathy
2) SLE
3) Amyloidosis
4) Hep C/ Hep B/ HIV
5) Myeloma
6) Pregnancy

Question 19

1) What is the most common cause of nephrotic syndrome in children?
2) What is the most commonnephrotic syndrome overall?
3) What is the most common cause of nephrotic syndrome in adults?

Answer 19

1) Minimal change disease
2) Diabetic nephropathy.
3) Focal segmental glomerulosclerosis

Question 20

1) What percentage of adult nephrotic syndrome is caused by minimal change disease?
2) In minimal change disease, what changes are seen on:

a) light microscopy
b) immunofluorescence
c) electron microscopy

Answer 20

1) about 25%.
2a) minimal change seen (as per the name)
2b) occasional IgM immunoglobulins.
2c) effacement of podocytes and podocyte foot processes.

Question 21

In membranous glomerulonephritis, what changes are seen on:

a) light microscopy
b) immunofluorescence
c) electron microscopy

Answer 21

a) mesangial expansion and capillary wall thickening
b) IgG and C3 proteins
c) GBM thickening due to sub epithelial deposits (‘spikes’ can be seen upon silver staining due to these deposits).

Question 22

Describe the deposits that can be seen on electron microscopy of a renal biopsy in membranous glomerulonephritis.

Answer 22

In idiopathic disease, these deposits are made up of IgG4, but they are made up of other IgG deposits in secondary disease (due to malignancy infection, immunological disease or drugs).

Question 23

What is the mechanism of damage in membranous glomerulonephritis?

Answer 23

Immune deposits damage the podocytes, allowing proteins to be filtered through.

Question 24

What is present in 70-80% patients with idiopathic membranous glomerulonephritis?

Answer 24

Anti-phospholipase A2 receptor antibody.

Question 25

Describe the basic treatment for membranous glomerulonephritis.

Answer 25

BP control Immunosuppression in those at high risk of progression Treatment of the underlying cause in secondary disease (here, it is possible for proteinuria to remit).

Question 26

Describe the basic treatment for minimal change disease.

Answer 26

``` Prednisolone initially (1mg/kg for 4-16 weeks) Longer term immunosuppression (cyclophosphamide/ calcineurin inhibitors) for frequent relapses. ```

Question 27

In focal segmental glomerulosclerosis, what changes are seen on: a) light microscopy b) immunofluorescence c) electron microscopy

Answer 27

a) focal segmental sclerosis within the glomerulus b) no abnormalities c) GBM thickening

Question 28

1) Why does FSGS result in decreased urine output? 2) Why does proteinuria occur in FSGS? 3) Name 3 secondary causes of FSGS.

Answer 28

1) Because of the decrease in filtration to parts of the glomerulus. 2) Because sclerosis can lead to damage in surrounding podocytes. 3) HIV, heroin use, lithium use, lymphoma or kidney scarring due to other GN.

Question 29

Describe the basic treatment for FSGS.

Answer 29

BP control Corticosteroids are 1st line in primary idiopathic disease Calcineurin inhibitors are 2nd line in primary idiopathic disease Plasma exchange/ Rituximab can be used for recurrence of FSGS in transplants

Question 30

Where is membranoproliferative glomerulonephritis more common and why?

Answer 30

More common in low and middle income countries due to infection.

Question 31

Name the 2 types of membranoproliferative glomerulonephritis and describe them.

Answer 31

1) Immune complex associated: driven by increased or abnormal immune complex deposition in the kidney and complement activation. 2) C3 glomerulonephropathy: due to a genetic or acquired defect in the alternate complement pathway.

Question 32

1) What is seen upon renal biopsy in membranoproliferative glomerulonephritis? 2) What distinguishes immune-complex associated disease from C3 glomerulonephropathy?

Answer 32

1) A proliferative glomerulonephritis with electron dense deposits. 2) Immunoglobulin deposits seen in immune complex associated disease.

Question 33

Describe the basic treatments for membranoproliferative glomerulonephritis.

Answer 33

BP control Treat underlying cause in immune complex disease Immunosuppression if no underlying cause found and there is a progressive decline in renal function. There are currently no treatments to block or modify C3 activation

Question 34

What is nephritic syndrome often caused by?

Answer 34

An immune response triggered by infection or other disease which causes inflammation in the glomerulus. Often, the capillary endothelium and basement membrane are damaged.

Question 35

What can cause red blood cell casts to be present in urine in nephritic syndrome?

Answer 35

Inflammation can cause bleeding into the kidney tubules which can cause red blood cell casts to be present in the urine.

Question 36

What causes a sterile pyuria in nephritic syndrome?

Answer 36

Due to glomerular inflammation, white blood cells are usually recruited to the area and can leak through capillaries, causing a sterile pyuria (WBCs present but no infection).

Question 37

1) What can cause oliguria and a potential AKI in nephritis syndrome? 2) What is another sign of nephritic syndrome which is caused by decreased GFR?

Answer 37

1) Inflammation that occurs in the glomerulus reduces the GFR by reducing fluid moving through. 2) Azotemia (retention of urea) or hypertension due to up regulation of RAAS.

Question 38

Name 8 possible signs of nephritis syndrome.

Answer 38

``` Proteinuria (typically <3.5g/24 hours) Haematuria Azotemia RBC casts (acanthocytes) Oliguria Antistreptolysin O titres HTN Sterile pyuria (presence of leukocytes but no infection). ```

Question 39

Name 7 possible causes of Nephritic syndrome.

Answer 39

1) Rapidly progressive glomerulonephritis 2) Anti-GBM disease (Goodpastures disease) 3) ANCA associated GN 4) Immune complex GN 5) Membranoproliferative GN 6) Henoch-Schönlein Purpura 7) Alport syndrome

Question 40

1) Generally, what is nephrotic syndrome due to? | 2) Generally, what is nephritic syndrome due to?

Answer 40

1) It is normally proteinuria due to podocyte pathology. 2) It is haematuria ± proteinuria due to inflammatory damage (if a GN process causes scarring, this is what leads to the addition of proteinuria to haematuria).

Question 41

1) What is the most serious form of glomerulonephritis? 2) Describe the damage caused by RPGN. 3) Name 3 diseases which cause RPGN.

Answer 41

1) RPGN. 2) Diffuse, proliferative and crescentic. 3) Anti-GBM disease, small vessel/ ANCA vasculitis and immune complex GN (such as SLE). **IgA nephropathy and membranous GN can 'transform' to become more rapidly progressive.

Question 42

1) When does RPGN occur? | 2) What is RPGN characterised by?

Answer 42

1) When any aggressive GN rapidly progresses to renal failure over days or weeks. 2) Loss of GFR >/= 50% with the presence of extensive glomeruli-crescents. It rapidly progresses to renal failure over days/ weeks.

Question 43

1) In RPGN what causes crescents to form in glomeruli? 2) In RPGN, rupturing of the glomerular capillary wall causes what 4 types of cells to accumulate within the Bowman's space? 3) What does inflammation in the Bowman's space then lead to?

Answer 43

1) Crescents are formed after the rupturing of the glomerular capillary wall. 2) Macrophages, fibroblasts, fibrin and epithelial cells. 3) Inflammation causes cytokine release, promoting proliferation of parietal cells, signifying severe injury.

Question 44

Describe the basic treatment for RPGN.

Answer 44

Corticosteroids and cyclophosphamide. | Further treatment depends on the aetiology.

Question 45

Describe the basic pathophysiology go anti-GBM disease (good pastures disease).

Answer 45

Auto-antibodies (anti-GBM antibodies) are produced to type IV collagen which is present in glomerular and alveolar basement membranes.

Question 46

How does anti-GBM disease often present?

Answer 46

As acute renal disease (oliguria/ anuria, haematuria, AKI, renal failure) with crescent formations as well as with lung diseases such as pulmonary haemorrhage (SOB and haemoptysis). ** A small proportion will have isolated lung presentations.

Question 47

In anti-GBM disease, what can be seen upon immunofluorescence of a renal biopsy?

Answer 47

Linear deposition of antibodies along the glomerular basement membrane.

Question 48

Describe the basic treatment for anti-GBM disease.

Answer 48

Plasma exchange to remove antibodies, corticosteroids and cyclophosphamide.

Question 49

1) What does ANCA stand for? 2) What does ANCA associated GN cause? 3) In ANCA associated GN, what can be seen upon immunofluorescence?

Answer 49

1) Anti-neutrophil cytoplasmic antibody. 2) Pauci-immune necrotising crescentic GN. 3) Few or not immune deposits (as per the pathological term 'Pauci' which is latin for meaning few or little).

Question 50

Which type of glomerulonephritis accounts for the majority of RPGN cases?

Answer 50

ANCA associated glomerulonephritis.

Question 51

Name 3 types of ANCA associated glomerulonephritis.

Answer 51

1) Granulomatosis with polyangitis (Wegener's granulomatosis) 2) Eosinophilic granulomatosis with polyangitis (Churg-strauss syndrome) 3) Microscopic polyangitis **They are all forms of renal vasculitis.

Question 52

1) What are ANCAs produced by and what do they target? | 2) What are the two main types of ANCA?

Answer 52

1) Produced by plasma cells to target proteins with neutrophil granules and/or monocyte lysosomes. 2) Perinuclear ANCA (pANCA) and cytoplasmic ANCA (cANCA). **atypical ANCA (X-ANCA also exists).

Question 53

What do the following anti-neutrophil cytoplasmic antibodies act against: 1) pANCA 2) cANCA

Answer 53

1) Target myeloperoxidase in proteins which activates neutrophilic granules. 2) Target neutrophil peroxidase/proteinase 3 which activates macrophage and monocyte lysosome functions as well as neutrophils.

Question 54

What is the overall result of the action of the ANCAs?

Answer 54

Activation of macrophages and neutrophils causes renal vasculitis.

Question 55

1) Which disease are pANCAs most commonly seen in? 2) Which disease are cANCAs most commonly seen in? 3) The presence of which type of ANCA is associated with ulcerative colitis in 80% of patients?

Answer 55

1) Microscopic polyangitis. 2) Granulomatosis with polyangitis. 3) atypical ANCAs (X-ANCA). **Can also be associated with Crohn's disease but only in 20% patients.

Question 56

Name 5 clinical presentations of ANCA associated GN.

Answer 56

1) Malaise 2) Myalgia 3) Arthralgia 4) Flu-like symptoms 5) AKI

Question 57

1) In ANCA associated GN, what causes acute inflammation and necrosis? 2) Which cells infiltrate the damaged area as 2nd line after neutrophils in ANCA associated GN? 3) What chronic changes occur in ANCA associated GN as a result of the inflammation?

Answer 57

1) Extravasation and infiltration of neutrophils. 2) Monocytes. 3) Scarring and fibrosis.

Question 58

Describe the basic management principles for ANCA associated GN.

Answer 58

Induction of remission using steroids and rituximab/ cyclophosphamide and then maintenance therapy with azathioprine, mycophenalate or rituximab for at least 12 months.

Question 59

What distinguishes immune complex glomerulonephritis from other forms of glomerulonephritis?

Answer 59

Immune deposits in the glomeruli which stain upon immunofluorescence. **Serologic and histological findings will point to the underlying disease.

Question 60

Name the 3 types of immune complex GN.

Answer 60

1) IgA nephropathy 2) Post-streptococcal GN 3) Lupus nephritis

Question 61

Describe the pathophysiological mechanism which underlies all types of immune complex GN.

Answer 61

Immune complex deposition in the glomerulus which activates the classical complement pathway resulting in inflammation and low levels of C3 and C4.

Question 62

1) Describe the immune complex deposits in IgA nephropathy. | 2) Describe a typical presentation of IgA nephropathy.

Answer 62

1) Mesangial and glomerular capillary IgA deposits. 2) Asymptomatic non-visible haematuria OR episodic visible haematuria usually occurring within 12-72 hours of an infection.

Question 63

1) What is the commonest primary GN in high income countries? 2) Give two signs of IgA nephropathy. 3) What does renal biopsy in IgA nephropathy show?

Answer 63

1) IgA nephropathy. 2) HTN and proteinuria usually <1g. 3) IgA deposition in mesangium.

Question 64

Describe the basic management of IgA nephropathy.

Answer 64

ACEi/ARB to reduce proteinuria and protect renal function. Corticosteroids and fish oil if there is persistent proteinuria >1g despite 3-6 months of ACEi/ARB + a GFR >50.

Question 65

Give 2 factors associated with post streptococcal GN.

Answer 65

1) Deposition of immune complexes (streptococcal antigens) forming sub epithelial humps. 2) Presence of anti streptococcal antibodies int he blood.

Question 66

Describe the clinical presentation of post-streptococcal GN.

Answer 66

Can occur about 2 weeks after a throat infection or 3-6 weeks after a skin infection with presentation varying from haematuria to acute nephritis.

Question 67

Name 4 signs or symptoms of post-streptococcal GN.

Answer 67

1) HTN 2) Haematuria 3) Oedema 4) Oliguria

Question 68

Give 4 diagnostic indicators of post-streptococcal GN.

Answer 68

1) Evidence of streptococcal infection 2) Increased anti-streptolysin O titre 3) Increased anti-DNAse B 4) Decreased C3.

Question 69

Describe the basic treatment for post-streptococcal GN.

Answer 69

Supportive. Antibiotics to clear nehpritogenic bacteria.

Question 70

State 2 distinguishing features of lupus nephritis.

Answer 70

1) Presence of ANA 2) Full house immunofluorescence staining (IgG, IgM, IgA, C3, C1q) **may also be anti-dsDNA antibodies

Question 71

1) How can kidney damage as a result of lupus nephritis present? 2) In lupus nephritis, where is immune complex deposition seen?

Answer 71

1) As nephritis or nephrosis. | 2) In the mesangium, subendothelium and subepithelium.

Question 72

Describe 5 clinical features which may be present if a patient were to present with lupus nephritis.

Answer 72

1) Rash 2) Photosensitivity 3) Ulcers 4) Arthritis 5) Serositis 6) CNS effects 7) Cytopenias 8) Renal disease

Question 73

Describe the basic treatment for stage I/II lupus nephritis.

Answer 73

ACEi/ARB for renal protection and hydroxychloroquine for extra renal disease.

Question 74

Describe basic treatment for stage III/IV/V lupus nephritis.

Answer 74

Immunosuppression required; mycophenolate, glucocorticoids, cyclophosphamide, rituximab.

Question 75

Describe membranoproliferative glomerulonephritis.

Answer 75

Not a disease in itself but a pattern of disease/ injury seen in GN and in nephrotic syndrome. Can have both nephrotic and nephritic pictures.

Question 76

How is membranoproliferative GN diagnosed and what are 3 distinguishing factors?

Answer 76

Diagnosed based on biopsy with renal histopathology showing: 1) mesangial cell expansion 2) GBM thickening 3) 'Tramtrack' findings with double contour on the GBM.

Question 77

1) What are the 2 types of membranoproliferative GN? | 2) State the sub -classifications of these types.

Answer 77

1) Immune complex mediated and complement mediated. 2) Immune complex mediated = primary (idiopathic) or secondary (due to infection, autoimmune disease or paraproteinaemia). Complement mediated = primary (idiopathic) or genetic (complement dysregulation).

Question 78

1) In immune complex mediated membranoproliferative GN, how does complement activation occur? 2) In complement mediated membranoproliferative GN, how does complement activation occur?

Answer 78

1) Complement activation occurs by the classical pathway which promotes the inflammatory response. 2) Direct activation of the alternate pathway which promotes the inflammatory response.

Question 79

Describe the difference in laboratory findings between immune complex mediated and complement mediated membranoproliferative glomerulonephritis.

Answer 79

1) Immune complex mediated = normal or mildly decreased C3 and low serum C4 2) Complement mediated = low serum C3 and normal C4 due to activation of alternate pathway.

Question 80

What is Henoch-Schönlein Purpura?

Answer 80

Small vessel vasculitis and systemic variant of IgA nephropathy with IgA deposition in skin, joints and gut in addition to in the kidney.

Question 81

Give 4 possible features of the clinical presentation of Henoch-Schönlein Purpura.

Answer 81

1) Purpuric rash on extensor surfaces. 2) Flitting polyarthritis 3) Abdominal pain (GI bleeding) 4) Nephritis

Question 82

Describe how Henoch-Schönlein Purpura can be diagnosed.

Answer 82

Diagnosis is usually clinical. Confirmed with positive immunofluorescence for IgA and C3 in the skin. Renal biopsy is identical to IgA nephropathy (mesangial and glomerular capiallary IgA deposits).

Question 83

Describe the basic management for Henoch-Schönlein Purpura.

Answer 83

Renal disease is managed as IgA nephropathy (ACEi/ARB to reduce proteinuria and protect renal function, then corticosteroids and fish oils if persistent proteinuria >1g despite ACEi/ARB). Steroids may be used for gut involvement.

Question 84

What causes Alport syndrome?

Answer 84

X-linked recessive gene mutation causing abnormalities in type IV collagen which prevents the kidneys from properly filtering blood.

Question 85

Why can aport syndrome also cause sensorineural hearing loss and vision abnormalities?

Answer 85

Because type IV collagen is also important in the organ of corti and for lens and retina shape in the eye.

Question 86

Name 6 signs and symptoms that could be features of the clinical presentation of Aport syndrome.

Answer 86

1) Haematuria 2) Proteinuria 3) Oedema 4) Osteodystrophy 5) Sensorineural hearing loss 6) Vision abnormalities (anterior lenticonus)

Question 87

Describe the basic management for those with Aport syndrome.

Answer 87

For most it can lead to ESRF, so a renal transplant will be required (this can run the risk of anti-GBM disease as graft type IV collagen may be recognised as foreign).

Question 88

What can the use of nephrotoxic drugs cause?

Answer 88

Use of nephrotoxic drugs can potentially precipitate an AKI or can worsen existing CKD.

Question 89

What causes the afferent arteriole to normally have a widen lumen than the efferent arteriole?

Answer 89

Prostaglandin mediated vasodilation of the afferent arteriole and angiotensin-II mediated vasoconstriction of the efferent arteriole. **This creates a pressure gradient across the glomerulus.

Question 90

What will happen if there is decreased blood flow through the afferent arteriole?

Answer 90

The efferent arteriole will need to vasoconstrict in order to compensate for the pressure difference.

Question 91

How can ACE inhibitors and angiotensin receptor blockers cause a decrease in GFR?

Answer 91

They block angiotensin-II (main mediator of EA vasoconstriction) > dilated afferent arteriole > decreased resistance > increased outflow of blood > reduced pressure gradient > reduced GFR.

Question 92

Describe the effect of NSAIDs on the kidney.

Answer 92

Use of NSAIDs reduce the production of prostaglandins, leading to vasoconstriction of the afferent arteriole and a reduced GFR. In order to maintain the GFR, the efferent arteriole then needs to vasoconstriction to maintain the pressure gradient.

Question 93

List the drugs which should be stopped or adjusted in the case of an AKI or CKD.

Answer 93

D - diuretics A - ACEis/ARBs M - Metformin N - NSAIDs

Question 94

Name 3 diseases of renal vasculature.

Answer 94

Renal artery stenosis Renal artery aneurysm Atheroembolic renal disease

Question 95

Why does HTN occur secondary to diseases of renal vasculature?

Answer 95

HTN occurs secondary to these diseases due to renal hypoperfusion causing activation of the RAAS.

Question 96

How can renal vascular disease lead to glomerulosclerosis?

Answer 96

RAAS activation > HTN > atherosclerosis > narrow lumen > reduced kidney perfusion > macrophage recruitment to the area > increased TGF-B1 > Mesangial cell regression > depletion of extracellular matrix > glomerulosclerosis.