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Delta Med - Renal > Renal 2 - Kidney transplant > Flashcards

Renal 2 - Kidney transplant Flashcards

1
Q

What are living donor criteria for transplant?

A

Willing, informed, over 18yo
Spouse or relative
Compatible blood type and tissue type, negative x-match
normal kidneys, negative family history, pHx
acceptable comorbidities and surgical risk

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2
Q

What are deceased donor critieria for transplant?

A

Brain dead in ICU, relative consent, any age
absence of malignancy, uncontrolled infection
ATN is OK

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3
Q

What is associated with deceased cardiovascular donors?

A

Higher risk of delayed graft function

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4
Q

What is increased in donors post transplantation?

A

SBP and proteinuria
30% reduction in GFR
Overall mortality is = to the general population when compared to controls who would have been eligible for transplantation

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5
Q

What are components of the immunology of transplantation?

A

ABO compatibility (less of an issue now)
Tissue typing - HLA
Panel reactive antibody test (PRA)

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6
Q

What are features of hyperacute rejection?

A

Rare, early and untreatable
Pre-formed antibodies, on table, black kidney, anuria.
Predictable by cytotoxic crossmatch.
Pathology = vascular thrombosis, PMNs, infarction

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7
Q

What are features of acute rejection?

A

Common (15-25%), early (1 week, peaks 3 months), treatable - prednisone
T-cell mediated (classical)
Diagnosed by Bx (DDx ATN, drugs, obstruction etc.)
Pathology:
cellular/interstitial - tubulitis, infiltrate
vascular/glomerular - endothelialitis
antibody mediated - PMNs, C4d+

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8
Q

What are features of chronic rejection?

A

common (30%+), late, no specific treatment
unknown aetiology - immune plus non-immune
progressive renal dysfunction, proteinuria and HTN
Diagnosed clinically +/- Bx, DDX GN, drugs, hypertension.
Path - glomerulopathy, chronic interstitial nephritis, vessels.

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9
Q

What are findings in chronic allograft nepropathy?

A 
tubular atrophy
intesrtitial fibrosis
patchy infiltrate
arteriolar hyalinosis
glomerulopathy - glomerulosclerosis, rarely MCGN
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10
Q

What is the number 1 cause of late transplant failure?

A

chronic allograft nephropathy (after death with a working allograft)

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11
Q

What are principles of immunosuppression in renal transplantation? (8)

A
  1. multiple agents to max efficacy, minimse toxicity
  2. tailor immunosuppression to risk of acute rejection
    - induction for hi risk patients
    - taper over time
  3. clinical and pharmacokinetic monitoring
    - CSA AUC
  4. prophylaxis for predictable SEs
    - osteoporosis
    - valaciclovir
  5. avoidance of drug interactions
  6. manage risk of cancer and infection
  7. use newer agents
  8. acknowledge uncertain effects on chronic rejection
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12
Q

What are two examples of Ab induction agents?

A

Thymoglobulin

Basilixumab

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13
Q

What are features of thymoglobulin?

A

rabbit immunoglobulin, polyclonal
targets T-cells, ICAM etc.
causes significant depletion of T-cells
duration of effect is days
excellent for induction and acute rejection and vascular rejection
Issues - cytokine release, LVF, meningitis, cytopenias, neutralising ab, cancer and infection (70% increased risk of all cancer, infections esp PJP)

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14
Q

What are features of basilixumab?

A 
human/mouse Ab, chimeric
Targets CD25+ T-cells, IL-2r activated
Causes inactivation
Duration of effect is months
Useful for induction but NOT so for acute rejection
Cost
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15
Q

What are the predominant drugs in Signal 1 inhibition?

A

Cyclosporin - binds cyclophillin

Tacrolimus - binds FK-BP

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16
Q

What is the main outcome of signal 1 inhibition?

A

inhibit IL-2 generation
cornerstone of anti-rejection prophylaxis
tacrolimus is more potent and preferred
synergistic with other agents

Target B and T-cells

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17
Q

What are 5 key clinical issues with signal 1 inhibitors?

A

CYP450 interaction
Concentration dependent action and toxicities, need to monitor levels and concentrations.
CSA - measure peak, tacro, measure trough
Both nephrotoxic - key contributors to CAN
Aim for high exposure early, minimal exposure late

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18
Q

What are two anti-metabolites used in renal transplantation?

A

mycophenolates

azathioprine

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19
Q

What is the mechanism of action of mycophenolate?

A

more potent in 1st 12 months, and relatively leukocyte specific
Inhibits IMPDH(II) - preferential action against proliferating lymphocytes - binds tissue receptors
blocks de-novo purine synthesis, G1 arrest
mycophenolate sodium absorbed more distally - less GI toxicity
mycophenolate levels are lower with CSA
cause bone marrow suppression

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20
Q

What is the mechnism of mTOR inhibitors?

A

bind to FKBP-12 (signal 3 inhibition) - binds FK-BP
Rapa-FKBP complex binds to mTOR
Inhibits IL-2/co-stim triggered cell signalling
- inhibits DNA synthesis - p27 - cdk2 interference - g1 arrest
- protein synthesis - IL-2 IFNg, IL-4, IL-10 (lesser)

Blocks T-cells, B-cells and VSM

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21
Q

What is the advantage of everolimus vs CSA in renal transplant?

A

shown to cause better long term GFR

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22
Q

What is the best agent for the management of acute rejection, apart from Ab induction agents?

A

Tacrolimus

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23
Q

What is tacrolimus C/I with?

A

tacrolimus is contraindicated with cyclosporin

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24
Q

What are significant toxicities associated with CSA?

A 
Nephrotoxicity
Hypertension
Dyslipidaemia
Mild assoc DM
Avascular necrosis
Haemolytic uraemic syndrome
Hepatotoxicitiy
Mild issues with PO4/MG wasting

Significantly gum hyperplasia

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25
Q

Which immunosuppressant is ok in pregnancy?

A

Cyclosporin

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26
Q

What are significant toxicities associated with Tacrolimus?

A 
nephrotoxic (less so than CSA)
Hypertension
Lipids
Diabetes +++
Neurotoxicity +++
HUS
Liver toxicity
PO4/Mg wasting
alopecia
C/I in pregnancy
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27
Q

What are significant toxicities associated with rapamycin/sirolimus?

A 
NOT nephrotoxic
significant lipid derangement (KEY!)
thrombocytopenia +++
anaemia
Lung disease (reversible, non-infective)
slight GI toxicity
slight neurotoxicity
PO4/Mg derangement
Stomatitis
C/I in pregnancy
28
Q

What are significant toxicities associated with MMF?

A

Significant reduction in WCC/neutropenia
anaemia/thrombocytopenia/Bm suppression
GI upset +++
C/I in pregnancy

29
Q

What is the general management of acute rejection?

A

1) tissue Dx essential - following USS
2) IV methylprednisone - 90% effective
3) OKT3 or ATG lymphocyte depleting antibodies
- if steroid resistant or evidence of vascular rejection
- non-depleting antibodies not useful
- adjust other immunosuppressants
4. plasma exchange, IVIg - if Ab mediated rejection
5. Rescue - refractory or recurrent rejection
- high dose tacrolimus and mycophenolate
6. reversal provides good prognosis
7. number of episodes predicts mortality

30
Q

What are some examples of early complications of kidney transplantation?

A

Infection - bacterial, viral - CMV, polioma/BK
Rejection - Acute
Drugs - tremor, ARF, GI, mood, bone (MMF)
Tumours - 2-3x risk, PTLD (EBV related), KS (HHV8+ve)
General - surgical complications

31
Q

What are some examples of late complications of kidney transplantation?

A

Infection - viral - warts, zoster, PCP (impaired cellular immunity)
Rejection - chronic, CAN
Drugs - hair (CYC), kidney, bone, CVS (except MMF)
Tumours - carcinoma, lymphoma
General - CVS disease, recurrence

32
Q

When is wound infection expected in transplant, and what are the clinical manifestations?

A

early

fever and cellulitis

33
Q

When is pneumonia expected in KTRs, and what are the features?

A

any time

fever, cough, hypoxia

34
Q

When is UTI expected in KTRs and what are the features?

A

early - sepsis

late - more benign, treat conventionally

35
Q

When is CMV expected in KTRs?

A

M2-12, features include fever, colitis, LFT derangement and lung involvement

36
Q

When is PCP expected in KTRs and it’s clinical features?

A

M3-12, dyspnoea, fever

37
Q

When is BK virus expected in KTRs and it’s clinical features?

A

graft dysfunction only, months 4-24

38
Q

when is HSV expected in renal transplantation?

A

Any time

39
Q

When is varicella expected, and what are it’s features?

A

any time, if primary, there is a 50% mortality rate

40
Q

When are fungal infections expected in KTRs and what are their clinical features?

A

post ART - fever, abscess (t-cell depleting therapy)

41
Q

When are decoy cells seen on urine?

A

in the presence of BK virus nephropathy

42
Q

What are features of the BK virus?

A 
DNA virus
Primary infection in childhood - persistence
Reactivated by:
- immunosuppression
- hormonal changes (preg, DM)
- tissue injury
- coinfection w HIV, CMV, HHV6
Asymptomatic
43
Q

What are features of BK nephropathy?

A 
interstitial nephritis
intranuclear inclusions
Tubular injury and necrosis
Evidence - SV40 antigen positive and Electron micro
Blood or urine PCR

Mx - reduce immunosuppression, unclear role of antivirals

44
Q

What is the role of prophylaxis in CMV and KTRs?

A

D+ to R- or D+ and Antibody Rx - 50% risk of CMV

valacyclovir has 65% reduction in CMV at 6 months and 50% reduction in acute rejection

45
Q

Osteoporosis prophylaxis in KTRs?

A

palmidronate pre and pst Tx prevents BMD loss

calcitriol plus Ca++

46
Q

What is the primary cause of death with a functioning graft?

A

Cardiovascular disease

47
Q

What is the most common cancer in KTRs?

A

Skin cancer most common, 70% by 30 y post transplant.
80% will have a cancer of some description by 30 years.
40% have solid organ.
Bulk of skin cancers are SCC or BCC

48
Q

What are risks for disease recurrence and graft loss in KTRs?

A

Risk exists for subjects with
- glomerulonephritis
- metabolic Dz (DM, oxalosis)
- malignancy
Disease recurrence doubles the risk of graft loss at 5 years
Risk of graft loss increases with time - diabetes, common after 10 years, glomerulonephritis

49
Q

What proportion of patients have GN recurrence post transplant?

A

6-19.4%

50
Q

What are predictors of GN recurrence post transplant?

A

rapid original course to renal failure
FSGS/MCGN
live/hla matched donor (Paed FSGS)
recurrence in previous graft

Rx - FSGS - screen ACR, Rx pheresis (removal of suPAR)
Vasculitis - steroids and cyclophosphamide

51
Q

What is the effect of steroids in recurrent IgA nephropathy post transplantation?

A

reduce the rate of IgA nephropathy recurrence related graft loss

52
Q

What is appropriate treatment of ABMR?

A

increase steroids
increase MMF
find a new donor

53
Q

What are the two organ transplants associated most strongly with CKD?

A

Intestine
Lung
Heart

54
Q

What is the strongest risk factor for CRF in non-renal tx patients?

A

GFR

55
Q

What proportion of transplant recipients develop NODAT?

A

25-40%

56
Q

What immunosuppressant is not implicated in NODAT?

A

MMF

57
Q

What causes insulin resistance in NODAT?

A 
steroids
CNIs, mTOR
inflammation
HCV, CMV
Obesity
Inactivity
58
Q

What causes insulin deficiency in NODAT?

A 
tacrolimus >> CSA
mTOR
age
insulin degradation
(tacro inhibits pancreatic insulin secretion)
59
Q

What other medication is assocaited with NODAT?

A

sirolimus is associated with NODAT, regardless of CNI usage. Sirolimus and CSA has highest prob of developing NODAT

60
Q

What is the key impact of NODAT on transplant patients?

A

increases rates of death with a functioning transplant

61
Q

What glomerulonephritis is least likely to recur?

A

post streptococcal glomerulonephritis

62
Q

What agents induce t-cell lysis?

A

thymoglobulin

63
Q

Which agents primarily interrupt signal 1 of t-cell activation during acute rejection?

A

tacrolimus

cyclosporin

64
Q

What agents are effective in treating acute allograft rejection?

A

thymoglobulin
mycophenolate (high dose)
tacrolimus
rapamycin

65
Q

Which medication is least likely to contribute to the development of diabetes after transplantation?

A

Myophenolate

66
Q

What are risk factors for CAN?

A

excess or inadequate CNI exposure
prior acute rejection
presence of donor specific antibodies.

Delta Med - Renal (3 decks)

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