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RACP 2024 > Renal > Flashcards

Renal Flashcards

1
Q

What are causes of HLA sensitisation prior to renal transplant?

A
  1. Previous transplant with poor HLA mathing
  2. pregnancies
  3. blood transfusions
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2
Q

What influence does HLA antibodies have on renal transplant?

A

Reduces graft survival but still achieve better survival than dialysis

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3
Q

What immunosuppression is used in renal transplantation?

A

Basiliximab induction = anti-CD25 (IL-2R)
Prednisolone
Tacrolimus = calcinuerin inhibitor
Mycophenylate = antimetabolite

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4
Q

What is basiliximab?

A

Human/mouse chimeric mAb against IL-2R (CD25) present on activated T-cells to reduce rejection

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5
Q

What is ATG? What is it’s role in renal transplant and risks?

A

Rabbit polyclonal Ab (thymoglobulin) that targets T-cells
Reduces acute rejection
Increased risk of infection and malignancy (esp PTLD in EBV donor+ recipient-)

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6
Q

What are pros and cons of using Tacrolimus over cyclosporin for renal transplant?

A

Pros:
- less acute rejection
- less de novo Donor Specific Antibodies (chronic graft rejection and loss)
- less gum hypertrophy
- less hirsitism
- less drug interaction

Cons:
- more post transplant diabetes
- low magnesium/phosphate
- more neurotoxicity
- more hair loss

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7
Q

Are tacrolimus and cyclosporin safe in pregnancy?

A

Yes

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8
Q

What is the mechanism of action of mycophenylate?

A

Inhibits IMPDH involved in purine synthesis

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9
Q

What interaction occurs with mycophenylate and ciclosporin?

A

Mycophenylate lower ciclosporin levels (but doesn’t affect tacrolimus)

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10
Q

What are the pros and cons of mycophenylate compared to azathioprine?

A

Pros:
- less acute rejection
- no interaction with allopurinol
- no issue in TPMT deficiency

Cons:
- more diarrhoea
- not safe in pregnancy (need to use azathioprine pre conception)

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11
Q

What is the mechanism of action of sirolimus and everolimus?

A

Bind FK binding protein and inhibit mTOR to inhibit IL-2 signalling

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12
Q

Are mTORi (sirolimus, everolimus) safe in pregnancy?

A

No

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13
Q

What is the most common cause of graft loss post renal transplant?

A

Death

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14
Q

What are early and late causes of death with graft function?

A

Early:
- infection (33%)
- cardiovascular (29%)
- cancer (7%)

Late:
- cancer (29%)
- cardiovascular (22%)
- infection (13%)

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15
Q

What are the early and late causes of renal graft loss (that are not death)?

A

Early (1st year):
- graft thrombosis/technical error (37%)
- rejection (17%)
- GN (3%)

Late:
- chronic allograft nephropathy (60%)
- GN (6%)
- Acute rejection and non-adherence (4%)

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16
Q

What is chronic allograft nephropathy?

A

Multifactorial:
- chronic CNI toxicity
- chronic antibody mediated rejection (unresolved early rejection, non-adherence, donor specific antibodies)

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17
Q

What is the most common cause of delayed graft function?

A

Post ischaemic ATN

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18
Q

What are risk factor for post-ischaemic ATN as a cause for delayed graft function?

A
  • deceased donor (uncommon in live)
  • donor AKI
  • donor age
  • DCD
  • cold ischaemia time
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19
Q

What are causes of delayed graft function other than post-ischaemic ATN that need to eb excluded?

A
  • Graft thrombosis (Day 1 USS)
  • obstruction or urine leak
  • rejection (needs biopsy)
  • Early disease recurrence (FSGS, TMA, oxalosis)
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20
Q

What are causes of early worsening graft function?

A
  • acute rejection (biopsy)
  • CNI toxicity
  • renal artery stenosis
  • obstruction/leak/collection post stent removal
  • BK nephropathy
  • recurrent disease (FSGS, aHUS)
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21
Q

What are the two types of acute renal transplant rejection?

A
  • T-cell mediated
  • Antibody mediated
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22
Q

What are risk factors for acute renal transplant rejection?

A
  • previous HLA sensitisation
  • pre-transplant antibodies against donor
  • younger recipient with older donor
  • prolonged ischaemia time
  • delayed graft function
  • HLA mismatches
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23
Q

How is acute renal transplant rejection managed?

A

T-cell mediated:
- IV methylpred for 3 days
- optimise maintenance immunsuppression
- ATG if steroid resistance

Antibody mediated:
- plasma exchange
- IVIg
- consider rituximab

Need PJP prophylaxis
CMV prophylaxis or pre emptive monitoring

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24
Q

What is the most important HLA matching in terms of long term outcomes and sensitisation for subsequent transplant?

A

DQ

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25
Q

What is BK and its relevance to renal transplant? How is it managed?

A

Polyoma virus that can cause nephropathy

Screened for with serum PCR in first 12 months
Reduce antimetabolite when viraemia detected
Biopsy if graft dysfunction to exclude concurrent rejection - see intranuclear viral staining + SV40 in medulla

No specific anti-viral, give IVIg or steroid

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26
Q

What CMV prophylaxis should be in renal transplant?

A

Depends on donor status:
D+R- = 6 months prophylaxis with valganciclovir

D-R+ = 3 months prophylaxis with valganciclovir OR pre emptive monitoring

D-R- = none unless ATG used

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27
Q

How is CMV infection treated in renal transplant?

A

PO double dose valganciclovir OR IV ganciclovir
Foscarnet or cidofovir if resistant

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27
Q

How can skin cancers be prevented post transplant?

A
  • sun protection
  • Switch CNI to mTORi
  • avoid azathioprine
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28
Q

What COVID anti-virals interact with tacrolimus?

A

Paxlovid (remdesivir and molnupiravir do not)

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29
Q

What are the most common causes of renal artery stenosis?

A
  • atherosclerotic disease (60-80%)
  • fibromuscular dysplasia (10-20%)
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30
Q

What are the clinical features of fibromuscular dysplasia?

A

Affect F:M 3:1
60% involve renal artery (35% bilateral)
String of beads appearance in mid to distal renal artery
ischaemia rare
poor repsonse to intervention

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31
Q

What are clinical features of atherosclerotic renal artery stenosis?

A

Older age
M = F
Affects ostial/proximal portion of renal artery, can be bilateral
Can result in ischaemia
Less amenable to intervention

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32
Q

What is the pathophysiology of renovascualr hypertension?

A

Reduced renal blood flow results in activation of renin (needs 80% stenosis to see reduced blood flow)

Renin cleaves Angiotensinogen to angiotensinI, which is activated to angiotensinII by ACE

AngiotensinII results in:
- vasoconstriction
- renal sodium retention
- aldosterone secretion
- hypertrophy and remodelling of LV and vessels
- Sympathetic activation

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33
Q

What is pressure natriuresis?

A

Increased renal perfusion in contralateral kidney in unilateral renal artery stenosis results in increased sodium excretion

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34
Q

What is Pickering syndrome?

A

In bilateral renal artery stenosis or solitary kidney unable to do pressure natriuresis resulting in sodium and fluid retention, which results in pulmonary oedema

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35
Q

What features are suggestive of renal artery stenosis?

A

HTN age < 30 or > 50
Abrupt onset HTN
Acceleration of previously stable BP
Malignant HTN
Accelerated retinopathy
Flash pulmonary oedema
AKI with ACEi

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36
Q

What is the sensitivity and specificity of renin and aldosterone levels in renal artery stenosis?

A

Both are low!

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37
Q

What is the diagnostic tests can be used for renal artery stenosis?

A

Doppler ultrasound
CT with contrast
MRI with contrast
Nuclear scan

Gold standard = angiography

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37
Q

How is renal artery stenosis managed?

A

BP management with RAAS blockade
CV risk modification
Angioplasty for FMD, only considered in atherosclerotic if flash pulmonary oedema or progressive CKD

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38
Q

What s the definition of CKD?

A

eGFR < 60 AND evidence of kidney damage (proteinuria) on more than 2 occasions over at least 3 months

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39
Q

What are the different stages of kidney function?

A

1 = GFR > 90
2 = GFR 60-89
3a = GFR 45-59
3b = GFR 30-44
4 = GFR 15-29
5 = GFR < 15 or on dialysis

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40
Q

What is the role of each of these segments of the nephron?
Glomerulus
Juxtaglomerular apparatus
Tubules

A

Glomerulus = filtration

Juxtaglomerular apparatus = autoregulation

Tubules = sodium, water, potassium, acid/base and other electrolyte balances

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41
Q

How should proteinuria be treated?

A

RAAS blockade (ACEi or ARB)
SGLT2i

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42
Q

What are BP targets in CKD?

A

Aim < 140/90 if no albuminuria
Aim < 130/80 if albuminuria

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43
Q

What is the biggest cause of anaemia in CKD?

A

Iron deficiency (followed by EPO deficiency)

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44
Q

Through what mechanism does CKD result in acidosis?

A

Loss of ability to synthesize ammonia and secrete hydrogen

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45
Q

What is the role of sodium bicarbonate in CKD?

A

May slow progression in moderate CKD

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46
Q

What is the cause of hyperkalaemia in CKD?

A

Decreased clearance
Tubulointerstitial dysfunction
RAAS inhibitors

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47
Q

What factors increase phosphate excretion in the urine?

A

PTH
Klotho
FGF23

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48
Q

What is the function of FGF23?

A

Suppresses phosphate reabsorption
Increases phosphate excretion
Reduces 1,25 Vitamin D activation

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49
Q

What happens to levels of the following in CKD
FGF23
1,25 vitD
PTH

A

FGF23 increases
1,25 vitD decreases
PTH increases

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50
Q

What is the target phosphate level in CKD?

A

aim for normal range

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51
Q

How is AKI defined?

A

Using KDIGO:
- serum Cr increase by >26.5 umol/L in 48h
- increase serum Cr >1.5x normal in last 7 days
- urine volume < 0.5 mL/kg/h for 6 hours

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52
Q

What makes the kidney vulnerable to injury?

A

High metabolic demand marginal oxygenation to outer medulla (proximal tubule and loop of henle)

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53
Q

What are renal causes of AKI?

A
  • glomerulonephritis
  • acute tubular necrosis
  • acute interstitial nephritis
  • acute microvascular disease
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54
Q

What is the pathophysiology of acute tubular necrosis?

A
  • ischaemic (extension of pre-renal AKI)
  • toxic (myoglobin, aminoglycosides, IV contrast, chemotherapies)
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55
Q

What are biopsy features of acute interstitial nephritis?

A

Increased cellular infiltrate

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56
Q

What are causes of acute interstitial nephritis?

A

Drugs:
- beta lactams
- PPIs
- NSAIDs
- immunotherapy

Infection

Immune:
- Sjogren’s
- sarcoidosis
- IgG4 disease

Idiopathic

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57
Q

What are aetiologies of acute miscrovascular AKI?

A
  • thrombotic microangiopathy: HUS-TTP
  • DIC
  • catastrophic anti-phospholipid syndrome
  • systemic sclerosis
  • cholesterol emboli
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58
Q

How does urinary sodium help to demonstrate the cause of AKI?

A
  • low urinary sodium = pre renal
  • high urinary sodium = ATN
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59
Q

What do hyaline casts in urine indicate?

A
  • reduced renal perfusion
  • composed of uromodulin formed in loop of henle
  • seen in exercise and dehydration
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60
Q

What doe renal tubular epithelial cells (RTEC) in urine indicate?

A

ischaemic or toxic tubular injury (ATN)

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61
Q

What do granular casts in urine indicate?

A

ATN

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62
Q

What do white cell casts in the urine indicate?

A

AIN

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63
Q

What do dysmoprhic red cells and red cell casts indicate in the urine?

A

Glomerular haemorrhage, especially in proliferative glomerular lesion

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64
Q

What are contraindications to kidney biopsy?

A
  • kidney failure
  • coagulopathy (antiplatelets, anticoagulation)
  • bilateral cysts
  • uncontrolled hypertension
  • hydronephrosis
  • UTI
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65
Q

What are the indications for RRT in AKI?

A
  • acidaemia
  • hyperkalaemia
  • toxins
  • overlaod
  • uraemia (pericarditis, encephalopathy)
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66
Q

Where are the glomeruli in the kidney?

A

In the cortex

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67
Q

What are the 3 layers of the glomerulus?

A
  • endothelial layer
  • GBM (negatively charged)
  • podocyte foot processes
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68
Q

What is the criteria to diagnose nephrotic syndrome?

A

Proteinuria > 3.5g/24 hours, hypoalbuminaemia, generalised oedema, hyperlipidaemia

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69
Q

What is the criteria of nephritic syndrome?

A

Haematuria with RBC casts and dysmorphic RBCs
Often seen with oliguria, hypertension and progressive reduction in GFR

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70
Q

Do you need proteinuria to diagnose nephritis?

A

No

71
Q

What is the commonest glomerular disease worldwide?

A

IgA nephropathy

72
Q

What is the size of albumin and filtration slits in the glomerulus?

A
  • albumin: 7.2 nm
  • smallest filtration slits: 8 nm
73
Q

Where in the kidney is water actively reabsorbed independent of sodium?

A

Collecting duct via AQP2 channel stimulated by ADH

74
Q

What proportion of sodium is reabsorbed in the collecting duct and what hormone influences this?

A

1-2%
Aldosterone

75
Q

What proportion of sodium is reabsorbed in the following parts of the tubule:
- proximal convoluted tubule
- thick ascending loop
- distal convoluted tubule

A
  • proximal convoluted tubule: 65-70%
  • thick ascending loop: 25%
  • distal convoluted tubule: 5%
76
Q

Through what mechanism is sodium reabsorbed from the urine?

A

Na/K ATPase in tubular epithelial cells pushes 3Na out of the cell in exchange for pulling 2potassium in, creating intracellular Na deficiency which is then reclaimed from the urine

77
Q

Where is the majority of water reabsorbed in the renal tubule?

A

PCT (follows sodium)

78
Q

Where is potassium secreted in the renal tubule?

A

Collecting duct

79
Q

What proportion of K+ is reabsorbed in the following parts of the renal tubule?
- PCT
- LOH
- DCT
-CD

A
  • PCT: 45-50%
  • LOH: 40-45%
  • DCT: 0
    -CD: 0 (actively secreted
80
Q

Where in the renal tubule is the majority of the following reabsorbed?
-Ca
- Mg
- Phosphate
- HCO3

A
  • Ca: PCT (70%)
  • Mg: LOH (60-70%)
  • Phosphate: PCT (70-80%)
  • HCO3: PCT (85-90%)
81
Q

How do diuretics cause secondary hyperaldosteronism?

A

Inhibit Na reabsorption causing vascular volume contraction, increasing aldosterone.
This leads to tubular K and H loss and results in hypokalaemia and metabolic alkalosis

82
Q

How do potassium sparing diuretics cause hyperkalaemia and metabolic acidosis?

A

Antagonise aldosterone leading to K and H retention

83
Q

How does the PCT reabsorb sodium?

A

Through apical Na-H exchange protein
Requires regeneration of HCO3 by carbonic anhydrase

84
Q

What is the mechanism of action of acetozolamide?

A

Carbonic anhydrase inhibitor, prevents HCO3 regeneration resulting in less Na (and therefore water) reabsorption
Chance of metabolic acidosis

85
Q

What is fanconi syndrome?

A

Fanconi syndrome is a defect of proximal tubule HCO3 regeneration resulting in proximal renal tubular acidosis, leading to malabsorption of various electrolytes and substances that are usually absorbed by the proximal tubule

86
Q

What are causes of fanconi syndrome?

A

Inherited:
- cystinosis
- galactosemia
- herediatry fructose intolerance
- tyrosinemia
- Wilson disease
- lowe syndrome
- dent disease
- mitochondrial cytopathies
- glycogenosis
- idiopathic

Acquired:
- nucleoside reverse transcriptase inhibitors
- cisplatin
- azathioprine
- gentamicin
- monoclonal gammopathy
- lead poisoning
- AKI
- beestings
- Legionella pneumonia

87
Q

What is the role of carbonic anhydrase in the PCT?

A

When Na is reabsorbed from urine in exchange for H, H combines in the urine with HCO3 to form H2CO3.
Carbonic anhydrase on the cell membrane cleaves this to H2O + CO2
The CO2 diffuses into the cell and carbonic anhydrase facilitates the formation of H2CO3
H2CO3 can then release H+ and HCO3-

This regenerates H+ and HCO3- for ongoing reabsorption and maintains pH

88
Q

How does the thick ascending loop of henle reabsorb sodium?

A

Via N/K/Cl transporter (1Na, 1K, 2Cl)
Calcium is passively reabsorbed as K is returned to the urine

89
Q

Why do thiazide diuretics result in hypercalcaemia?

A

Thiazides inhibit sodium reabsorption in DCT
Proximal parts of the tubule compensate for this, including thick ascending loop, to increase sodium reabsorption therefore increase calcium reabsroption

90
Q

How does frusemide cause hypocalcaemia?

A

Blocks sodium reabsorption in loop of henle.
Calcium is passively reabsorbed along with sodium here, so reduces calcium reabsorption

91
Q

What is mechanism of action of frusemide?

A

Loop diuretic = inhbits Na-K-2Cl cotransporter (NKCC2) in thick ascending lip

92
Q

What is Bartter syndrome?

A

Defect in sodium reabsorption in thick ascending limb resulting in sodium wasting in urine
See metabolic acidosis, hypokalaemia and low/N BP

93
Q

What are the 5 types of Bartter syndrome?

A

1: Na-K-2Cl mutation
2: ROMK mutation
3: CIC-kb mutation
4: Barttin mutation
5: upregulation of CaSR

94
Q

Where in the body is CaSR found?

A

Parathyroid gland
Basolateral membrane of cells in TAL of LOH

95
Q

What is the role of CaSR in renal tubule?

A

Calcium binding to CaSR inhibits K channel (luminal) and Na-K ATPase (basolateral) in TAL
Also reduces paracellular carrier proteins for calcium

Net effect is to reduce paracellular calcium and magnesium reabsorption

96
Q

What is the pathological basis of familial hypocalciuric hypercalcaemia?

A

AD mutation in CaSR

97
Q

How can hyperparathyroidism and FHH be distinguished?

A

Hyperparathyroidism should have high urinary calcium

98
Q

What are clinical features of familial hypocalciuric hypercalcaemia?

A
  • mild hypercalcaemia
  • hypocalciuria
  • inappropriately high/normal PTH
  • high/normal serum magnesium
  • hypophosphataemia
99
Q

How is FHH managed?

A

Benign - no specific management

100
Q

How is sodium reabsorbed in the DCT?

A

Via NaCl co-transporter (NCCT)
(site of thiazide action)

101
Q

What is Gitelman syndrome?

A

Impaired NCCT function

Hypokalemia
Metabolic acidosis
Hypomagnesaemia (TRPM6 also inhibited)
Low BP
Hypocalciuria

102
Q

How can Bartter and Gitelman syndrome be distinguished?

A

Bartter: high urine calcium
Gitelman: low urine calcium

103
Q

What is Addison disease?

A

Cortisol insufficiency from impaired adrenal function results in inability to excrete K+ and H+, results in metabolic acidosis

104
Q

What is diabetes insipidus?

A

ADH deficiency (central) or inability to respond to ADH (nephrogenic) resulting in polyuria

105
Q

How does lithium cause diabetes insipidus?

A

Decreases expression of AQP2 genes

106
Q

What is the role of JGA?

A

JGA = macula densa of distal tubule in close proximity to juxtaglomerualr cells of afferent and efferent arterioles + extraglomerular mesangial cells

When low BP sensed by JG cells or low Na in MD cells or beta-adrenergic stimualtion, JG cells secrete renin

107
Q

What is the mechanism of action of each of the following:
- renin
- ACE
- Angiotensin II
- Aldosterone

A
  • renin: cleaves angiotensinogen to angiotensin I
  • ACE: cleave angiotensin I to angiotensin II
  • Angiotensin II: stimulates aldosterone secretion AND constricts blood vessels
  • Aldosterone: increases sodium and water retention
108
Q

Which glomerular arteriole is greater affected to constrict in response to angiotensin II?

A

Efferent

109
Q

What is the rationale for using ACEi/ARB in proteinuria?

A

Reduces intraglomerular pressure and filtration by decreasing efferent tone >afferent, thus reduces proteinuria

110
Q

What is the mechanism of aldosterone?

A

Bonds to intracellular mineralocorticoid receptor in principle cells of collecting duct
Increases expression of Na/K ATPase to increase sodium reabsorption. This increases K+ lost in urine.

Also act on alpha intercalated cells to stimulate hydrogen ATPases which increase H+ excretion

111
Q

What are clinical features of primary aldosteronism?

A

Hypertension
Mild hypokalaemia
Mild metabolic alkalosis
Polyuria

112
Q

What is the most common cause of primary hyperaldosteronism?

A

Idiopathic bilateral adrenal hyperplasia

113
Q

What are the 3 ways that hyperkalaemia can potentiate metabolic acidosis?

A
  1. K+/H+ exchange across cell membranes
  2. K+ competes with H+ for secretion in collecting duct
  3. Hyperkalemia reduces renal ammonia production and inhibits H+ excretion
114
Q

What is the primary urinary buffer H+?

A

Ammonia (NH3)

115
Q

How does hypokalemia cause alkalosis?

A

Augments H-K-ATPase which secrete H+ to reabsorb K+ in type A intercalated cells of collecting duct

116
Q

What is renal tubular acidosis?

A

Normal anion gap metabolic acidosis with preserved GFR
Either with hypokalaemia (1 or 2)
OR hyperkalaemia (4)

117
Q

What are the different types of renal tubular acidosis?

A

Type 1: defect in distal tubule H+ secretion

Type 2: defect in proximal tubule HCO3 reabsorption

Type 4: decreased production of or reduced response to aldosterone

118
Q

What is the most common type of renal tubule acidosis?

A

Type 4

119
Q

How can type 1 and 2 renal tubular acidosis be distinguished?

A

Both are normal anion gap metabolic acidosis with hypokalaemia

Type 1 = distal
- urine pH > 5.5 (urinary alkalosis as no H in urine)
- renal stones due to citrate reabsoprtion in attempt to compensate by reabsorbing alkali
- no fanconi syndrome
- Associated with Sjogrens, SLE, PBC, autoimmune hepatitis

Type 2 = proximal
- urine pH < 5.5 (distal tubules secrete excess H)
- no renal stones
- fanconi syndrome (glycosuria, phosphaturia, uricaciduria, aminoaciduria)
- associated with myeloma, tenofovir, acetazolamide

120
Q

How are type 1 and 2 renal tubular acidosis treated?

A

Alkali (bicarbonate or potassium citrate)
Potassium replacement

121
Q

What are causes of type 4 renal tubular acidosis?

A

Diabetic nephropathy (most common)
NSAIDs
ACEi
Cyclosporin
Tacrolimus
High dose heparin
Spirinolactone

122
Q

How is type 4 renal tubular acidosis treated?

A

Fludrocortisone if not overloaded or hypertensive
Thiazide or loop diuretic if hypertensive or overloaded

123
Q

What event cause hyperparathyroidism in CKD?

A
  • phosphate retention (initial trigger)
  • decreased calcium concentration
  • decreased calcitriol concentration
  • increased FGF23 concentration
  • reduced CaSR, FGF23R and klotho receptors
124
Q

Where is glucose primarily reabsorbed in the kidney?

A

Proximal tubule, 97% by SGLT2i

125
Q

What is the principle of convection with regard to dialysis?

A

The ‘drag’ of solutes across a semi-permeable membrane
Removes larger sized molecules and plays a bigger role in PD

126
Q

What is the preferred access for haemodilation?

A

Arteriovenous fistula

127
Q

What is the pathophysiology of dialysis disequilibrium syndrome?

A

Clearance of solutes (urea) extracellularly creates osmolar difference ICF vs ECF, water shifts into ICF and results in cerebral oedema

128
Q

Where is most of the resistance for the movement of solutes in peritoneal dialysis?

A

Blood vessel wall

129
Q

What is the optimal position for a PD catheter?

A

In pelvis below pelvic rim

130
Q

What is the composition of PD fluid?

A
  • glucose = key osmotic agent, can worsen diabetic control (icodextrin does not)
  • physiologic Na, CCa, Cl, Mg
  • lactate as a buffer
131
Q

How is dialysis adequacy assessed?

A

PD: 24 hour urine and diasylate collection and calculate weekly Kt/V and CrCl + amount of fluid removed

HD: Kt/V or urea reduction ratio

132
Q

What are the acute and chronic indications for dialysis?

A

Acute:
- fluid overload unmanageable with diuretic or fluid restriction
- refractory metabolic acidosis
- refractory hyperkalaemia
- Significant uraemic complications (encephalopathy, pericarditis)

Chronic:
- weight loss/ reduced appetite
- difficulty concentrating
- weakness

133
Q

What is the typical eGFR when dialysis is commenced?

A

5-8 (not an indication)

134
Q

What is the mechanism of the following:
- haematuria
- proteinuria

A
  • haematuria: breaks in GBM
  • proteinuria: podocyte injury
135
Q

What is the definition of nephrotic syndrome?

A
  • proteinuria > 3g/day
  • hypoalbuminaemia
  • oedema
136
Q

What is the mechanism of thrombosis in nephrotic syndrome?

A
  • urinary loss of anticoagulants
  • hepatic overproduction of procoagulants (in response to low alb)
  • platelet dysfunction
137
Q

What serum albumin indicates prophylactic anticoagulation should be used?

A

< 20

138
Q

What anticoagulant is the standard of care in the nephrotic syndrome?

A

Warfarin

139
Q

What is the histopathological finding in membranous nephropathy?

A

Subepithelial spikes

140
Q

What are the causes of membranous nephropathy?

A
  • idiopathic (70%); often anti-PLA2R positive
  • autoimmune (SLE, MCTD)
  • infection (Hep B, C, malaria, syphilis)
  • heavy metals
  • cancer (lung, breast, colon)
141
Q

What is the 1/3 rule of membranous nephropathy?

A

30% spontaneous complete remission
30% partial remission
30% progress to ESRF (if untreated)

142
Q

What features are very high risk for membranous nephropathy?

A
  • rapid eGFR decline
  • severe nephrotic syndrome
  • PLA2R > 150
143
Q

How is membranous nephropathy treated?

A
  1. Low risk
    - normal eGFR< protein < 3.5g/day
    - symptomatic support
  2. moderate risk
    - proteinuria >4g/day for > 6/12
    - watch and wait OR rituximab OR Calcineurin inhibitor
  3. High risk
    - proteinuria >8, eGFR > 60, PLAR2R > 50
    - rituximab +/- Calcineurin inhibitor OR cyclophosphamide/steroid
  4. Very high risk
    - rapid eGFR decline, severe nephrotic, PLA2R > 150
    - cyclophosphamide/steroid
144
Q

What are the two podocytopathies?

A

Minimal change disease
Focal segmental glomerulosclerosis

145
Q

What are the LM and EM findings of minimal change disease?

A

LM = normal
EM = foot process effacement

146
Q

What is the typical presentation of minimal change disease?

A

Sudden onset, severe nephrotic syndrome
Typically very steroid responsive

147
Q

How is minimal change disease treated?

A

Initial = high dose prednisolone

Relapsing/steroid dependent = rituximab, CNI, MMF or cyclophosphamide

148
Q

What are the features and treatment of primary FSGS?

A
  • sudden onset severe nephrotic syndrome
  • high risk for recurrence post transplant

Rx:
- prednisone (max 6/12)
- CNI if no response to pred (2nd line is MMF or rituximab or clinical trial)

149
Q

What should be suspected in patients with FSGS who do not respond to immunosuppression?

A

Genetic cause

150
Q

What is adaptive FSGS?

A

Hyperfiltration mediated segmental foot process effacement and proteinuria without nephrotic syndrome

common in diabetes, prematurity and indigenous

151
Q

What is the most common primary glomerular disease?

A

IgA nephropathy

152
Q

What is the pathophysiology of IgA nephropathy?

A

Autoantibodies against galactose deficient IgA1 form immune complexes and deposit in mesangium. This causes cellualr injury resulting in cellular proliferation and inflammation

153
Q

What are the secondary causes of IgA nephropathy?

A
  • liver disease
  • infection
  • IBD
  • rheumatological conditions
  • lymphoma
154
Q

What is the MEST-C score for IgA nephropathy?

A

Mesangial hypercellularity
Endocapillary hypercellularity
Segemental glomerulosclerosis
Tubular atrophy
Crescent

155
Q

What is the most common clinical presentation of IgA nephropathy?

A

Asymptomatic microscopic haematuria, proteinuria

(2nd in mucosal infection with macroscopic haematuria)

156
Q

How is IgA nephropathy managed?

A
  1. Supportive care
    - RAS blockade
    - BP control
    - Na restriction
    - lifestyle and CV risk mod
    - SGLT2i
  2. Clinical trial if proteinuria >1g/day
  3. PO steroids (max 6/12)
157
Q

What are histopathological features of infection-related GN?

A
  • endocapillary proliferation
  • IHC for C3 +/- IgG, IgA, IgM
  • EM for hump shaped subepithelial deposits
158
Q

What are clinical features of infection-related GN?

A
  • haematuria
  • hypertension
  • AKI
  • Low C3
  • bacterial or viral infection
159
Q

What features are associated with IgA- dominant infection related GN?

A
  • elderly
  • diabetics
  • staph infection
160
Q

How is infection related GN treated?

A
  • treat underlying cause
  • supportive care
  • steroids only in severe cases due to risk of reactivating infection
161
Q

What is the pathophysiology of anti-GBM?

A

Capillaritis in kidney and lung due to autoimmune reaction to NC1 domain of alpha3 chain of Type IV collagen

162
Q

What are clinical features of anti-GBM disease?

A
  • haematuria with rapidly progressive kidney injury
  • pulmonary haemorrhage
  • HLA-DR15
  • relapse uncommon
163
Q

How is anti-GBM disease treated?

A
  • plasma exchange
  • steroids
  • cyclophosphamide
164
Q

What self-antigens in pauci-immune GN are associated with the following ANCA patterns ?
pANCA
cANCA

A

pANCA = MPO
cANCA = PR3

165
Q

What ANCA patterns are seen with the following vasculitides?
MPA
GPA
eGPA

A

MPA = pANCA = MPO
GPA = cANCA = PR3
eGPA = usually negative

166
Q

What vasculitis more commonly affects the kidneys?

A

MPA

167
Q

What ANCA vasculitis pattern is associated with higher risk of relapse?

A

PR3

168
Q

How is ANCA-associated vasculitis treated?

A

Steroids is mainstay in induction and mainstay
1. Induction
- rituximab (better than cyclophosphamide for PR3)

  1. Maintenance
    - rituximab (> azathioprine> methotrexate>mycophenylate)

(plasma exchange only if anti-GBM positive)

169
Q

What is the classical pattern of lupus nephritis on kidney biopsy?

A
  • immune deposits in subendothelial and subepithelial
  • IgG, IgA, IgM, C3 and C1q positive
170
Q

How is lupus nephriitis treated?

A
  • mesangial= treat extra-renal
  • membranous = RAS blockade, BP control, hydroxychloroquine, immunosuppression if nephrotic
  • proliferative = steroids + MMF or cyclophosphamide, MMF + CNI (voclosporin), OR Belimumab + MMF or CYC
171
Q

What is the mechanism of action of voclosporin?

A
  • CNI
  • no drug monitoring required
  • less metabolic impact
172
Q

What is the mechanism of action and indication of belimumab?

A
  • mAb against BAFF (B-cell activating factor)
  • proliferative lupus nephritis
173
Q

What are histopathological features of MPGN?

A
  • subendothelial deposits
  • mesangial expansion
  • GBM thickening with “tram track contour”
174
Q

What types of diseases demonstrate an MPGN pattern with positive Ig?

A
  • monoclonal gammopathies
  • infections
  • autoimmune disease
  • idiopathic
175
Q

What pattern of injury is seen with C3 glomerulopathy?

A

MPGN
- subendothelial deposits
- mesangial expansion
- GBM thickening with “tram track contour”

176
Q

What are mechanisms of C3 glomerulopathy?

A
  • C3 convertase autoantibody (nephritic factors)
  • Loss of factor H (genetic or autoantibodies)
  • C3 mutations
177
Q

How are C3 glomerulopathy treated?

A

Mild-Mod: supportive

Mod-severe: steroids + MMF

Refractory: eculizumab (anti-C5)

RACP 2024 (15 decks)

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