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Year 3 TCDs > Glomerulonephritis & Polycystic Kidneys > Flashcards

Glomerulonephritis & Polycystic Kidneys Flashcards

1
Q

What is glomerular disease?

A

A general term for a group of diseases which affect the glomeruli of the kidneys

It is a common cause of CKD + ESRD

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2
Q

Which 2 conditions are termed under “glomerular disease”?

A
  1. Glomerulonephritis: inflammation of the glomeruli
  2. Glomerulopathies: immune complex/complement deposition without inflammation

**Overlap exists of these 2 conditions in real life

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3
Q

How is glomerular disease staged?

A
  1. Based on the signs + symptoms –> glomerular syndromes
  2. Specific blood tests + urine tests –> primary (idiopathic) or secondary (due to specific cause) glomerulopathy
  3. Ultrasound kidneys
  4. Renal biopsy –> type of glomerular pathology
    - Minimal change
    - FSGS (focus segmental glomerular sclerosis)
    - Membranous
    * * Based on light/electron microscopy, immunohistochemistry
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4
Q

What are the 3 main types of glomerular pathology?

A
  1. Minimal change
  2. FSGS (focus segmental glomerular sclerosis)
  3. Membranous
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5
Q

Name 3 systems you would think of which can present with symptoms of fluid overload.

A
  1. Heart failure
  2. Liver failure
  3. Kidney failure
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6
Q

What is peri-orbital oedema and when does it commonly present?

A

Swelling of the eyelids (puffy eyelids)

Seen in children with glomerulonephritis

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7
Q

What two bed side tests should the GP do next if after their examination they feel it might be a renal problem. What are they looking for and why?

A
  1. Urine Dipstick Test:
    In glomerular diseases – blood and /or protein in the urine.
  2. Blood Pressure:
    Renal diseases result in inappropriate retention of salt and water, leading to hypertension.
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8
Q

The GP, Dr Paul finds Mr Smith, oedematous up to his thighs, but normotensive and urine dipstick showed 3+ protein.

What would his primary suspicion for this patient be?

A

A glomerular disease

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9
Q

What is the normal range for specific gravity?

A

Around 1.010

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10
Q

What are 3 causes of a low specific gravity?

A

Specific gravity = 1.00

  1. Excessive hydration
  2. Diabetes insipidus (deficiency/resistance to ADH)
  3. Acute tubular necrosis
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11
Q

What are 7 causes of a high specific gravity (1.035)

A
  1. Dehydration
  2. SIADH
  3. CHF
  4. Cirrhosis
  5. Glycosuria
  6. Proteinuria
  7. IV contrast recently
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12
Q

If regardless of hydration status the specific gravity remains 1.010, what does this indicate?

A

Advanced kidney failure

  • Kidneys lose the ability to regulate urine concentration
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13
Q

What is pH from urinalysis useful for diagnosing?

A
  1. Renal tubular acidosis
  2. Monitoring urine alkalization to prevent precipitation of myoglobin in rhabdomyolysis
  3. Aid the elimination of certain drugs (aspirin, methotrexate)
  4. Differentiation of different types of kidney stones
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14
Q

What does a low pH indicate on urinalysis?

A

Acidemia

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15
Q

What does a high pH indicate on urinalysis?

A

Alkalemia

  1. Distal renal tubular acidosis
  2. UTI secondary to urease-producing organisms (proteus, klebsiella)
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16
Q

What does glucose in the urine indicate?

A
  1. Hyperglycemia (glycosuria -> osmotic diuresis -> dehydration)
  2. Proximal tubule dysfunction (i.e. Fanconi syndrome)
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17
Q

What are 3 broad possible causes of blood (heme) in the urine?

A
  1. Hematuria of any cause (UTI, renal stone, GU malignancy, nephritic syndrome)
  2. Rhabdomyolysis
  3. Contamination with semen
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18
Q

What are 3 causes of protein in the urine?

A
  1. Glomerular disease (diabetic nephropathy)
  2. Overflow proteinuria (multiple myeloma, rhabdomyolysis, intravascular hemolysis)
  3. Post-renal proteinuria (UTI)
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19
Q

In what 4 conditions would you see high leukocytes with normal nitrites?

A
  1. Urological malignancy
  2. Chronic interstitial nephritis
  3. Interstitial cystitis
  4. Intra-abdominal inflammatory process adjacent to the GU tract
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20
Q

In what conditions are ketones detected in the urine?

A
  1. Ketoacidosis
    - Diabetes
    - Alcoholic
    - Starvation
  2. Ketogenic diet
    - Kids with epilepsy
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21
Q

Name 3 conditions when bilirubin/urobilinogen are present in the urine?

A
  1. Hemolysis
    - Elevated urobilinogen
  2. Biliary obstruction
    - Elevated bilirubin
    - Normal/decreased urobilinogen
  3. Liver disease
    - Variable bilirubin/urobilinogen
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22
Q

What is the normal excretion amount of protein in urine?

A

< 150mg

  • Albumin < 30mg
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23
Q

What is the gold standard for checking protein levels in the urine?

A

24h urine collection

For convenience: urine ACR, PCR

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24
Q

What test is important in the diagnosis of early diabetic nephropathy (reversible glomerular damage)?

A

Urine ACR

  • Albuminuria > 300mg/24h is detected on urine dipstick
  • UPCR in gms/24h is used to monitor this
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25
Q

What is glomerular filtration?

A
  • Process by which cells + large proteins are removed from the blood to create ultra filtrate
  • Occurs in the renal corpuscle
  • Is driven by opposing pressures exerted by the contents of the blood + ultrafiltrate
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26
Q

How does glomerulonephritis affect glomerular filtration?

A

Inflammation of the filtration membrane alters its permeability and inhibits proper filtration

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27
Q

What is the difference between hydrostatic + oncotic pressures?

A

Hydrostatic = push out
- Forces that blood + ultrafiltrate exert on filtration membrane

Oncotic = suck in
- Forces that proteins within the blood + ultrafiltrate exert to draw water towards them

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28
Q

What is the pathophysiology of glomerulonephritis?

A

Unknown but thought to be:

  1. Due to immunological response to a variety of aeitological agents
    - Group A strep
    - Viral infections: hepatitis C
    - Some drugs

Immunological Response:
A) Immunoglobulin and complement activation within the glomeruli (where the antigen is a structural component of the glomeruli e.g. Good Pastures antigen in the glomerular basement membrane)

B) The antigens may be trapped or deposited within the glomeruli

C) Trapping of circulating immune complexes (less common in human GN)

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29
Q

When abnormalities occur in the glomerulus patients what clinical syndromes can they present with?

A
  1. Isolated haematuria /proteinuria OR haematoproteinuria
  2. Nephrotic Syndrome (inflammation)
  3. Acute glomerulonephritis ( acute nephritic syndrome )
  4. Rapidly progressive glomerulonephritis (RPGN )
  5. Chronic Kidney Disease including ESRD
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30
Q

What is nephrotic syndrome?

A

Loss of protein because podocytes/basement membrane aren’t working properly (endothelial cells)

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31
Q

What are symptoms of nephrotic syndrome?

A
  1. Loss of 3.5g/day of protein
  2. Frothy urine
  3. Low albumin
  4. High lipids (serum + urine)
  5. Low AT-III (antithrombin 3) = hypercoagulable state = thrombosis in renal vein = DVT/PE
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32
Q

What is nephritic syndrome?

A

Immune complexes lodged in capillaries illicit immune response against capillaries + antigens
- White cells are recruited = inflammation!

  • RBCs + WBCs + proteins can get thru epithelial cells

(nephrotic range proteinuria as a result of nephritic syndrome)

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33
Q

What are the symptoms of nephritic syndrome?

A
  1. Hematuria + sediment in urine
  2. WBCs in urine
  3. Oliguria (glomerulus is damaged = low GFR)
  4. Hypertension (b/c of lack of filtration)
  5. Granular casts
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34
Q

What are the 4 stages of nephrotic syndrome?

A
  1. Minimal Change
    - Normal light microscopy / electron microscopy effacement of podocytes
    - Commonest cause in children
  2. Focal Segmental Glomerulosclerosis (FSGS)
    - Scarring in glomerulus – with only some glomeruli affected (focal) and only parts of individual glomerulus affected (segmental)
    - Common cause in adults
  3. Membranous Glomerulonephritis
    - Immune deposits on basement membrane and a second membrane forms over these deposits with irregular spikes where several immune complexes deposited
  4. Membranoproliferative Glomerulonephritis
    - Similar to membranous but immune deposits also present in mesangium, not just basement membrane
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35
Q

What are 5 secondary causes of nephrotic syndrome?

A
  1. Autoimmune (e.g. SLE)
  2. Infections (e..g. malaria, hepatitis B & C, HIV)
  3. Drugs (e.g. NSAIDs, pencilliamine)
  4. Heavy metals (e.g. gold, mercury)
  5. Tumours (solid tumours e.g. lung, colon and haematological malignancies e.g. multiple myeloma)
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36
Q

How can diabetes affect the kidneys?

A

Diabetic nephropathy

In late stages = nephrotic syndrome

Renal biopsy must be avoided. If done will see nodules in the mesangium known as Kimmelstiel-Wilson lesions

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37
Q

Name 2 causes of acute glomerulonephritis (acute nephritic syndrome)?

A
  1. Post streptococcal glomerulonephritis (GN)

2. IgA nephropathy (commonest GN worldwide)

38
Q

What is IgA nephropathy?

A

aka Berger’s Disease

Antibody IgA builds up in the kidneys = local inflammation = over time hampers kidney’s ability to filter waste from your blood

39
Q

What are the causes of IgA nephropathy?

A
  1. Asymptomatic with bloody urine that occurs 1-3d after URTI
  2. Gastroenteritis or UTI may cause this
  3. Strep GN develops 1-3wks following strep infection
40
Q

How is IgA nephropathy diagnosed?

A

Urinalysis = erythrocytes (RBCs) + mild proteinuria

Only biopsy can confirm diagnosis: mesangial IgA deposits
- Isolated microscopic hematuria is NOT an indication for biopsy

41
Q

How is IgA nephropathy treated?

A

Reassess at 6-12mo intervals if patient is normotensive, has minimal proteinuria, and normal GFR

  • BP
  • Urinalysis
  • U&E (GFR) at appointments
42
Q

What drug treatment is used for IgA nephropathy?

A

ACE-i/ARBs

  • once patient has developed hypertension and/or proteinuria (>0.5g/day)
43
Q

What is rapidly progressing glomerulonephritis?

A

Presents as nephritic syndrome

If not treated = life-threatening

Also termed crescentic glomerulonephritis:

  1. Glomerular hematuria (RBC casts or dysmorphic RBCs)
  2. Rapidly developing kidney injury over a few weeks-months progressing to kidney failure if not treated promptly
44
Q

Name 2 causes of large vessel vasculitis?

A
  1. Takayusa

2. Giant cell arteritis

45
Q

Name 2 causes of medium vessel vasculitis

A
  1. Polyarteritis nodosa

2. Kawasaki disease

46
Q

Name 2 causes of small vessel vasculitis

A
  1. ANCA associated
  2. Non-ANCA associated
    - HSP
    - Cryoglobinemia
    - SLE
47
Q

What is Takayasu vasculitis?

A
  • Affects aorta + major branches
  • Rare in this part of the world
  • Granulamatous inflammation: mononulcear infiltration, heals with fibrosis
  • pulseless disease
  • Renovascular HTN

Tx = steroids

48
Q

What is giant cell arteritis?

A
  • Elderly
  • Headache, polymyalgia, fever, weight loss
  • Raised ESR
  • Tender temporal artery with no pulse
  • Jaw claudication

Tx = high dose steroids to prevent blindness

49
Q

What is poylarteritis nodosa?

A
  • Not common in the UK
  • Necrotising arteritis (visceral arteries - supplying GI tract)
  • Not glomerulonephritis
  • Usually ANCA negative; associated with Hep B/C
  • Constitutional symptoms + peripheral neuropathy
  • Livedo reticularis (skin rash)

Cause: GI bleed, bowel infarction, renal artery aneurysms/infarction, hypertension

  • Diagnosis with angiogram

Tx = corticosteriods + cyclophosphamide (Hep B negative)

Antiviral + corticosteroids (Hep B positive)

50
Q

What is Kawasaki disease?

A
  • Rare in western world
  • Children affected
  • Muco-cutaneous lymphadenopathy (MCL) = oral ulcerations
  • Coronary artery vasculitis = MI (life threatening)

Tx = symptomatic + IV immunoglobulins in severe cases

51
Q

What are examples of ANCA associated vasculitis?

A
  1. Granulomatosis with polyangiitis (Wegener’s granulomatosis) = cANCA predominant
  2. Microscopic polyangiitis
  3. Eosinophilic granulomatous polyangiitis (Churg-Strauss syndrome) = pANCA predominant
    - Asthma + eosinophilia + neuropathy = classic triad
  4. Renal limited vasculitis
52
Q

What is ANCA?

A

anti-neutrophil cytoplasmic autoantibodies

pANCA = perinulcear staining (specific for myeloperoxidase enzyme)

cANCA = diffuse cytoplasmic staining (specific for proteinase-3 enzyme)

Both enzymes are stored in neutrophil granules + play major role in bacterial infections defence
pANCA = strong acid that kills bacteria

cANCA = digestion of bacterial cell wall

53
Q

What is the aetiology of ANCA vasculitis?

A
  1. Multi-factorial
  2. Genetic predisposition
  3. Environmental triggers: infection, silica, farming
54
Q

What is the pathogenesis of ANCA vasculitis?

A
  1. Priming of neutrophils -> expression of auto-antigen
  2. Binding of ANCA -> activation of neutrophils
  3. Adhesion + transmigration -> oxidative burst and release of ROS, cytokines -> tissue damage
55
Q

What are the clinical presentations of ANCA vasculitis?

A

Renal = RPGN

Lungs = granuloma or alveolar hemorrhage. Dyspnea, cough, hemoptysis

ENT = granuloma-rhinorrhea, crusting, epistaxis, stenosis, conductive deafness, nasal deformity

Skin rashes, joints, GI bleed, heart (Churg-Strauss), nervous system (peripheral neuropathy) also affected

56
Q

How is ANCA vasculitis diagnosed?

A
  1. ANCA antibodies (80-85%)
  2. Kidney biopsy (looking for neutrophils destroying glomerulus)
  3. Lung hemorrhage – CXR/CT
  4. CO transfer factor
  5. NCV (nerve conduction)
  6. ENT assessment (internal injuries in nasal tract)
57
Q

What is the treatment for ANCA vasculitis?

A

Induction of remission: cyclophosphamide + steroids

  • Cytotoxic = cyclophosphamide (destroys lymphocytes)
  • Takes 2 weeks to work

Maintenance of remission: azathioprine + steroids

  • For a period of 2 years otherwise disease will recur
  • 50% relapse in 5yrs

Other drugs used:

  • Methotrexate (less toxic than cyclophosphamide)
  • Mycophenolate mofetil (transplant medication)
  • Rituximab (monoclonal antibody that kills B cells)
  • Plasma exchange (exchange blood plasma)
58
Q

What blood tests would you do to investigate for a renal glomerular disease ? Think about the normal functions of the kidney as well.

A
  1. FBC
  2. Renal Profile
  3. Bone profile
  4. Lipid profile
  5. Coagulation screen
  6. Hba1c
  7. ESR/CRP
  8. Immunology screen
  9. Myeloma screen
  10. Hepatitis Serology
59
Q

What was the Urine Dipstick finding which prompted the Doctor to send the urine for PCR?

A

The urine dipstick test was 3 + positive for protein, which indicates there is severely increased (significant) proteinuria.

60
Q

FBC Hb 159g/l wcc 5.7 platelets 316
Renal Profile Na 138 K 4.1 Urea 6.5 Creatinine 97 egfr 70mls/min
Albumin 16 mmol/l ,rest liver function tests normal
Cholesterol 10.70 g/l
Urine Protein creatinine ratio 943 mg/ mmol of creatinine

What are your interpretations of the results? Do you think the patient has a nephrotic syndrome?

A

FBC and Renal function is normal. Patient has got heavy proteinuria , low albumin and high cholesterol levels. He also presented with a clinical picture of fluid overload. Anecdotally, puffiness around the eyelids are associated more commonly with renal cause of fluid overload.

Nephrotic syndrome

61
Q

What is the management for nephrotic syndrome?

A
  1. Salt restriction - no salt diet
  2. Fluid restriction - 1-1.5L for 24h
  3. Diuretics
    - To remove the peripheral odema
    - Over diuresis may cause pre-renal AKI, therefore monitor fluid loss by daily weights. Loss of weight should be no more than 500-750 mls a day.
  4. ACE-i/ARB
  5. Anticoagulation (higher risk of VTE)
62
Q

Why do we consider anti coagulation in heavily proteinuric patients?

A

Heavy proteinuria causes loss of Antithrombin 3, Protein C and S loss through the tubules. These proteins normally help blood to remain anti coagulated in the body. Loss of them makes the blood prone to clot.

63
Q

Where do the cysts in cystic kidney disease arise from?

A

Renal tubules

64
Q

What are the genetic causes of cystic renal disease?

A

Autosomal dominant:

  • ADPKD
  • Tuberous sclerosis
  • Von Hippel Lindau Disease
  • Medullary cystic disease

Autosomal recessive:

  • ARPKD
  • Juvenile onset nephrophthisis

X-linked:

  • Orofacial digital syndrome
  • Chromosomal disorders (trisomy 13/18/21)
65
Q

What are the non-genetic causes of cystic renal disease?

A
  1. Developmental Cysts
    - Medullary sponge kidney
    - Multicystic dysplastic kidneys
    - Pyelocalyceal cysts
  2. Acquired Cysts
    - Simple cysts
    - Acquired renal cystic disease
    - Hypokalemia related cysts
66
Q

What is the most common cause of renal failure due to a cystic renal disease?

A

ADPKD

  • 10% of dialysis population
67
Q

How can ARPKD be distinguished from ADPKD?

A

Inheritance pattern:

  • Recessive
  • Earlier age of onset
  • Obligate presence of liver disease (congenital hepatic fibrosis)
68
Q

What are simple renal cysts?

A
  • Become more common with age
  • Usually unilocular + located in the cortex
  • Kidneys don’t get enlarged by these cysts
  • > 30y people can have simple cysts
  • Classified by Bosnian classification to rule out the cancerous complex cysts
69
Q

What are acquired renal cystic diseases?

A
  • Patients who have had a long duration of dialysis can develop acquired renal cysts
  • Shrunken kidneys
  • No family history of cystic diseases
70
Q

What are the extrarenal associations with ADPKD?

A
  • Berry aneurysms -> SAH
  • Liver cysts
  • Pancreas cysts
  • Spleen cysts
  • Mitral valve prolapse
  • Divertucli
71
Q

What are the extra renal associations with von Hippel-Lindau disease?

A
  1. CNS hemangioblastoma
  2. Retinal angioma
  3. Renal lesions
72
Q

What investigations are used for cystic kidney diseases?

A

Renal ultrasound + CT

73
Q

What should you ask in the history of someone with glomerular disease?

A
  • known hypertension, proteinuria, hematuria
  • Recent URTI
  • Systemic symptoms (rash, joint pains, weight loss)
74
Q

What investigations should you do for glomerular hematuria?

A
  • Proteinuria
  • Renal impairment (may be normal on imaging)
  • Hypertension
  • Dysmorphic red cells/red cell casts
  • Renal biopsy
75
Q

How does IgA nephropathy present in the patient?

A

Macroscopic hematuria + pain following URTI

76
Q

What are the symptoms of ADPKD?

A
  • Abdo pain/side/lower back
  • Blood in urine
  • High BP
  • Kidney stones
  • Recurrent UTIs
  • Loss of kidney function (CKD, ESRD)
77
Q

What is the diagnostic criteria for polycystic kidney disease?

A

Modified Ravine’s criteria

  • Age 15-29 = 3+ cysts (unilateral/bilateral)
  • Age 30-39 = 3+ cysts
  • Age 40-59 = 2+ cysts in each kidney
78
Q

A patient with blood and protein in their urine will always have glomerulonephritis.

True/False?

A

False

79
Q

When an Urine dipstick is positive what is the first test you need to do?

A

Send urine for culture + sensitivity

80
Q

If patient has an Urinary Tract Infection (UTI), what are the parameters which may be positive on dipstick?

A
  1. Nitrites
  2. Leucocytes
  3. Blood + Protein
81
Q

If the patient urine dipstick is positive for invisible haematuria, which departments would you refer the patient to?

A
  1. Nephrology
    - They may have GN
  2. Urology
    - They may have cancer
82
Q

USS Kidneys are done to find out the type of Glomerulonephritides.

True/False?

A

False

83
Q

USS kidneys are done to rule out urinary tract obstruction (UTO).

True/False?

A

True

84
Q

RBCs when examined under the microscope can more commonly be dysmorphic if the RBCs are leaking from the glomeruli rather than leaking from a bleeding vessel from the ureters, bladder, urethra.

True/False?

A

True

  • B/c the biconcave shaped RBC gets squashed and loses their shape as they pass thru the glomerular capillaries
85
Q

What is the normal urine protein excretion in a day?

A

<150mg/24h

Consists of about 30mg albumin

Microalbuminuria is defined as excretion of 30-300mg/day of albumin

It’s an important test to indicate onset of diabetic nephropathy

86
Q

Nephrotic Range proteinuria is >3.5g/24hrs.

True/False?

A

True

87
Q

Nephrotic range proteinuria is very common in UTIs

True/False?

A

False

88
Q

Nephrotic Range proteinuria is very commom in bladder cancer.

True/False?

A

False

89
Q

Nephrotic range proteinuria is seen in glomerulonephritis.

True/False?

A

True

90
Q

Tolvaptan is a new drug approved by NICE for use in certain patients with ADPKD. The precautions needed to use this drug are?

A
  1. Patients need regular blood tests including U&Es + LFTs
  2. Annual MRI volume measurement of the kidneys
  3. Patient needs to drink plenty of fluids

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