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Aisha > Dunedin-Renal > Flashcards

Dunedin-Renal Flashcards

1
Q

When investigating vasculitis, which tissue biopsy has the highest yield?

A

Kidney

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2
Q

Discuss relapse rates of renal vasculitis PR3 vs MPO.

A

PRs 2 fold > than MPO

risk of relapse: prior relapse, lung disease, upper airways disease, persistently positive ANCA (PR3), bacterial and viral infection may trigger relapse

rising ANCA titres is not diagnostic of relapse

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2
Q

What is the management for renal vasculitis?

A

Induction therapy: cyclophosphamide and rituximab (for fertility preservation, malignancy risk and cumulative cycle exposure)

Steroids

Plasma exchange- debatable, use if advanced kidney injury or pulmonary haemorrhage

Avacopan: complement C5a receptor inhibitor.

Maintenance: rituximab, azathioprine, methotrexate and mycophenolate

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3
Q

What is the pathogenesis behind anti-GBM disease?

A

Anti body against NC1 domain of the alpha 3 chain of type 4 collagen
also recognise alpha 5 and 4 chains
rarely purely against alpha 4

autoantibodies activate the complement (alternative and classical) and T cell systems leading to damage

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4
Q

What does a biopsy show in anti-GBM?

A

Crescenteric proliferative GN with linear IgG basement membrane staining

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5
Q

What is the management of anti-GBM disease?

A

Basically the same as renal vasculitis

Plasmapheresis and immunosuppressive therapy
pulse methylpred, cyclophosphamide

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6
Q

What is de-novo anti-GBM disease?

A

Happens post transplant in patients with genetic COL4 abnormalities (thin basement membrane/alports syndrome)

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7
Q

What is the typical timing of post-strep GN?

A

1-3 weeks after a sore throat
1-6 weeks after other infective sites

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8
Q

What is the symptoms of post-step GN?

A

can be asymptomatic or symptomatic
in those symptomatic
- haematuria (macroscopic coke coloured)
- proteinuria (may be nephrotic range)
- HTN
- often profound swelling
- acute kidney injury

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9
Q

How to diagnose post-strep GP?

A

confirmed strep infection or consistent serology (streptozyme measures all 5)
- Anti-streptolysin (ASO), anti-hyaluronidase (AHase), anti-streptokinase (ASKase), Anti-nicotinamide-adenine dinucleotidase (anti-NAD) or Anti-DNase B antibodies

  • acute nephritic syndrome
  • C3 is low (due to activation of the alternate pathway) C4 normal
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10
Q

What is the treatment of post-strep GN?

A

treat infection, supportive therapy, Mx HTN (with loop diuretics), RAAS blockade if needed, dialysis if required

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11
Q

Causes of glomerular ischaemia

A

TMA
HUS
TTP
Hypertensive renal crisis
scleroderma renal crisis
pre-eclampsia

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12
Q

Pathophysiology of TMA/MAHA?

A

Endothelial injury/exposure –> platelet/fibrin clots –> mechanical damage to passing red cells –> capillary occlusion due to fibrin/platelet clot results in end organ injury –> platelet consumed –> passing red cells are broken into fragments or distorted into sperocytes (smaller hence microangiopathic)

alternative pathway constantly turning over and requirements active regulation to prevent injury to tissue

regulatory factors are complement factor H, CFI, membrane cofactor protein MCP (CD46) and others

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13
Q

Describe mechanisms of endothelial injury in HUS, TTP, Hypertensive, scleroderma and pre-eclampsia

A

HUS- shiga toxin mediated injury or abnormal regulation of the alternative complement pathway

TTP- von willebrand factor multimers causing endothelial injury

Hypertensive- ?direct pressure injury

Scleroderma- not clear what initiated injury but associated with other markers of disease severity and steroid exposure

Pre-eclampsia- likely placental derived factor (?sFLT-1)

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14
Q

Describe pathophysiology of complement mediated HUS

A

Loss of function variants in CFH, CFI or CD46 (regulatory) or gain of function variants in CFB or C3 (effector) results in over activity of alt pathway and endothelial injury (~60% of adult HUS)

Antibodies against the regulatory proteins can cause the same process (8-10% of adult HUS)

Generally a two hit phenomena where something else triggers TMA (this is a proportion of ST – HUS)

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15
Q

Describe pathophysiology of TTP

A

Deficient ADAMTS13 activity — TTP is caused by severely deficient activity of the ADAMTS13 (A Disintegrin And Metalloprotease with a ThromboSpondin type 1 motif, member 13) protease, typically described as an activity level <10 percent
* Cleaves vWF multimers
* In the absence ultra large multimers accumulate which accumulate on the endothelial surface and result in platelets attaching

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16
Q

Criteria to perform renal biopsy

A

*>1g proteinuria (may not if has been stable for a long time)
*Reduced eGFR
*Apparent hereditary disease if no gene test
*if the patient really wants to know

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17
Q

What is the most common type of GN?

A

IgA nephropathy

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18
Q

Describe the pathogenesis of IgA nephropathy

A

Abnormal circulating IgA is produced (the IgA is abnormal in that the hinge regions are poorly glycosylated) –> not able to be effectively cleared by the liver –> abnormal IgA is preferentially deposited in the mesangial cell –> these mesangial cells are transformed into a pro-inflammatory phenotype –> mesangial processes induce a abnormal podocyte response and local complement pathways are activated

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19
Q

Treatment of IgA

A

most of the time supportive
RAAS blockade
SGLT2 inhibition
immunosuppression (doesnt work in advanced fibrotic disease, can use steroids, targeted release budesonide, or mycophenolate)

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20
Q

What is non-specific mesangial proliferative GN?

A

Presents like IgA
biopsy looks like IgA without IgA
general therapy the same
role of immunosuppression is not defined

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21
Q

Genetic abnormalities in Alport syndrome?

A

disease-causing variants in genes encoding the alpha-3, alpha-4, and alpha-5 chains of collagen IV

These collagen IV alpha chains are normally located in various basement membranes of the kidney, cochlea, and eye

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22
Q

What is the mode of inheritance of aport syndrome?

A

majority X-linked
some autosomal recessive, autosomal dominant

COL4A3,4,5

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23
Q

How to diagnose alport syndrome

A

Genetic testing or renal biopsy
thin basement membrane disease

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24
Q

Is there haematuria in nephrotic syndrome?

A

Typically no, apart from FSGS

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25
Q

What is the most common cause of nephrotic syndrome?

A

Diabetic nephropathy

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26
Q

Newly diagnosed albuminuria in patient with T2DM?

A

If haven’t had DM for long, have no retinopathy or have haematuria then likely another cause and would consider biopsy

duration is more important than control

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27
Q

Management of nephrotic syndrome?

A

RAAS blockage- dual with MRA
Salt restriction
SGLT2 inhibition
loop diuretics to control swelling often at high dose

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28
Q

What are some causes of secondary FSGS?

A

Result of hyperfiltrative injury
*low nephron endowment/ CAKUT/prematurity of nephron loss
*Obesity
*Hypertensive injury
*Prior glomerular injury (Vasculitis)

Direct injury
*infection (HIVAN, parvovirus, HepC)
* Medications (heroin, interferon, bisphosphonates, anabolic steroids)

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29
Q

Describe Minimal change disease

A

Presentation: acute onset with heavy nephrotic syndrome
BP low, albumin low
may have history of atopy

note- pure MCD doesnt cause progressive CKD

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30
Q

Describe treatment of minimal change disease

A

Steroids

if steroid dependent or relapsing disease
- cyclophospamide
- cyclosporin/tacrolimus
- rituximab
- mycophenolate
- azathioprine

31
Q

Describe pathogenesis for primary FSGS/MCD

A

A circulating factor (suPAR, CLCF1 or microRNA’s) cause injury to podocytes

MCD benign end and FSGS is severe with progressive CKD and ESKD
Rate correlates with degree of proteinuria

Circulating factor results in recurrence post transplant often fulminantly. This is why FSGS can recur quickly after transplant

32
Q

Describe causes of of membraneous nephropathy

A

primary as a result of foot process antibody (90%)

Secondary: lupus, medications (eg NSAIDS, anti TNF, immune Cp inh et al), infection (hep B, hep C, syphilis), malignancy (prostate, lung, breast, bladder or GI)

33
Q

What is the most common medication causes membranoproliferative glomerulonephritis?

A

immune checkpoints

34
Q

Describe pathogenesis of membranous nephropathy

A

1) Phospholipase A2 receptor antibodies (high expressed on podocytes, unknown with triggers Ab formation), antibodies move through the GBM to deposit at the target antigen on the podocyte

Other antigens: neural epidermal growth factor-like 1 (NELL1) the most common
thrombospondin type 1-1 domain-containing 7a (THSD7A)

35
Q

What is the management of membranous nephropathy?

A

5-30% get spontaneous complete remission
standard proteinic kidney disease management
immunosuppression

36
Q

What is the final pathology of CKD?

A

Glomerular sclerosis (2* to FSGS) with associated proteinuria

37
Q

Action of angiotensin II in the kidney

A

-↑ IGP by efferent arteriole vasoconstriction
- Alters podocyte function causing proteinuria
– Stimulates proliferation of smooth muscle cells and cytokine release
- stimulates sympathetic NS

38
Q

Role of mRA when added to RAS blockage in CKD?

A

further reduction in proteinuria
reduced progression to ESRD
some evidence of cardiovascular benefit

39
Q

Role of finererone in CKD

A

It is a type of non-steroidal mRA (steroidal mRA include spironolactone and eplerenone) and has been shown to reduce cardiovascular and kidney failure outcomes in patients with T2DM

S/E- slight drop in BP, no sexual side effects, hyperkalaemia

40
Q

S/E of SGLT2

A

euglycaemic DKA
Glycosuria- increased UDI and increased topical candidiasis

41
Q

Role of semalutide in CKD and T2DM?

A

When used with SGLT2 Semaglutide reduced the risk of clinically important kidney outcomes and death from cardiovascular causes in patients with type 2 diabetes and chronic kidney disease.

42
Q

Is there a role for lipids in CKD?

A

*No mortality benefit when on haemodialysis
* reduction in atherosclerotic endpoints in dialysis patients

43
Q

What are the three parameters we use to assess bone pathology (TMV) in CKD?

A

Turnover, Mineralisation, Volume

44
Q

What are the major patterns of bone disease in CKD

A

*Osteitis fibrosa cystica- high turnover mediated by PTH

*Adynamic bone disease- low turnover

*Osteomalacia- low turnover with abnormal mineralisation

*Mixed

45
Q

Describe fibroblast growth factor 23

A

Circulating 32kDA peptide- derived from bone: klotho- co-receptor, expressed in kidney and parathyroid

Secreted by osteocytes and osteoblasts

reduced phosphate, vit D, PTH secretion

46
Q

Describe phosphate regulation in CKD

A

3 feedback loops

– FGF23 -↓ renal reabsorption, ↓ 1, 25 Vit D hydroxylation ↓ PTH release

– PTH -↓ renal reabsorption, ↑ bone turnover, ↑FGF23 and ↑ 1, 25 Vit D hydroxylation (↑PO4)

– 1, 25 Vit D -↑ renal reabsorption and gut absorption, ↑ FGF23 production and ↓ PTH release

47
Q

Describe calcium regulation in CKD

A

Decreased in response to increase phosphate, reduced 1,25 vit D, resistance to PTH induced release from bone

48
Q

How to treat high PTH in CKD

A

1) 1,25 Vit D or analogue supplementation
2) calcimemtics
3) surgery

49
Q

What Is hungry bone syndrome?

A

profound life threatening hypocalcaemia post PTHectomy

associated low phosphate and magnesium

50
Q

What is the value of correcting anaemia in CKD?

A

quality of life

dont correct too much! Hb >125-130 is associated with increase cardiovascular mortality and stroke

51
Q

What did the IDEAL trial show regarding CKD?

A

No benefit in starting dialysis early- wait until become symptomatic

52
Q

What is the role of PLA2R Ab in membranous nephropathy?

A

High level of PLA2R Ab associated with risk of progression and a low/negative or reducing level with remission

53
Q

Describe histology of membranoproliferative glomerulonephritis disease

A
54
Q

Describe the pathology of membranopoliferative glomerulonephritis

A

Immune complex monoclonal Ig mediated
*Infections (hep C (with EMC), hep B, chronic bacterial, fungal or schistosomal)
* Autoimmune (lupus (fullhouse IF), Sjogren’s or RA)
* Monoclonal gammopathies

Complement mediated (described 2007)
*C3 or C4 glomerulopathy
* C3 nephritic factor

No Ig or complement deposition
* Pattern may occur in the healing phase of multiple causes of acute glomerular injury

55
Q

C3 glomerulonephritis and post-strep glomerulonephritis are different.

A

Yes but hard to tell the difference
both result in low C3
A common pathology is due to abnormal regulation of the alternative complement pathway.

56
Q

What are eplets?

A

Eplets are small configurations of polymorphic amino acid residues on human leukocyte antigen (HLA) molecules

The same eplet may be on multiple HLA antigens and this is way exposure to one HLA antigen may generate ABs against multiple HLA types

57
Q

What is the immunosuppression for a renal transplant?

A

Induction therapy:
- IL 2 monoclonal (Basiliximab)
- Polyclonal (antithymocyte globulin)

Maintenance therapy
- Calcineurin inhibitor (cyclosporin or tacrolimus)
- antimetabolite (mycophenolate or azathioprine)
- steroid (prednisone)

58
Q

Acute allograft dysfunction by timing: Immediate, 1-12 weeks, >3 months

A
59
Q

What is found on the biopsy of a acute rejection kidney?

A

T lymphocytic infiltration

60
Q

What is the role of donor derived cell free DNA?

A

goes higher in acute rejection

60
Q

What is the treatment of acute rejection?

A

Methylprednisone 500g-1g daily for 3 doses
rescue dose MMF
modify CNI- change CyA to Tac
ATG
if antibody mediated Rituximab/PEx/IVIG

61
Q

What is the most common infection following a renal transplant?

A

urinary tract!

even later strep pneumonia is common

62
Q

What is the most common opportunistic infection post renal transplant?

A

CMV

63
Q

When do you have most risk of CMV infection in renal transplant?

A

Donor positive to recipient negative (give 6 months of prophylaxis)

if recipient positive and degree of immunosuppression

64
Q

How to treat CMV infection in renal transplant?

A

IV ganciclovir
if mild- oral valganciclovir, letermovir, or maribavir
treat until PCR negative and then suppressive therapy
reduce immunpsupression

65
Q

What is the reason for valganciclovir resistance? Maribavir, letermovir?

A

Valganciclovir due to variants in U54 and U97 genes

Maribavir u97 variants

Letermovir due to U56 variants

66
Q

What are symptoms of BK virus infection in renal transplant?

A

– Tubulointerstitial nephritis with allograft dysfunction
– Ureteric stenosis
– Haemorrhagic cystitis
– Systemic vasculopathy

thought to occur due to the injury in the renal tract during transplant process to influence virus reactivation

described as viral inclusions

RISKS: degree of immunosuppression, use of tacrolimus, donor age, ureteral stent, viral co-infection and others

Monitoring: monthly plasma viral load to 9 months and 3 monthly to 2 years.

can consider IVIG if reducing immunosuppression doesn’t work

67
Q

What is the prophylaxis for EBV in renal transplant?

A

Valganciclovir , reduce inmunosupresión

68
Q

What conditions can commonly occur after renal transplant?

A

FSGS
HUS
Membranoproliferative GN

69
Q

Common cause of late graft loss?

A

patient death
chronic rejection
recurrent GN

typical histological appearance: transplant glomerulopathy and interstitial fibrosis

70
Q

What is the most common cancer in patients with renal transplant?

A

SCC cancer

71
Q

Post-transplant lymphoproliferative disorder

A

b-cell monoclonal proliferation
frequently extra nodal
EBV associated
may reflect over immunosuppression

72
Q

What is the rate of post-transplant diabetes?

A

incidence of 10-15% at 1 year

73
Q

What immunosuppressive agents are diabetogenic?

A

Tacrolimus/cyclosporin direct islet cell toxicity
sirolimus diabetogenic
steroids insulin resistance

74
Q

Managing diabetes post-transplant?

A

aggressive insulin therapy early so we can prevent loss of islet cells. if later on then manage as you would normally with diabetes

75
Q

Describe electrolyte disturbance post transplant

A

hypomagnesemia as a result of CNI renal wasting

hypophosphataemia as a result of diuresis, increase PTH or a circulating factor which increases renal phosphate excretion now almost certainly identified as FGF 23

Aisha (33 decks)

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