Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Nefrologia PT > ASN QBank Pearls - Renal Transplant > Flashcards

ASN QBank Pearls - Renal Transplant Flashcards

1
Q

imunologia do tx

A

Major histocompatibility complex (MHC) is a family of genes that encodes HLA.

HLAs: Glycoprotein encoded by genes on chromosome 6. Unique like fingerprints. Immuno-dominant antigen for both humoral and cellular alloreactivity.

MHC I -> HLA Class I: HLA-A, HLA-B, HLA-C On all nucleated cells (also platelets). Not on RBCs

MHC II -> HLA Class II: HLA-DRB1, DRB3,4,5, HLA-DPB1, DPA and HLA-DQB1, DQA on B and certain T lymphocytes and Myeloid cells (antigen presenting cells (APC), Macrophages, Dendritic cells, activated human endothelial cells, BLy).

Epitopes: Hypervariable regions in the HLA distal domains and are recognized as foreign.

Non HLA: Eg: Angiotensin type 1 receptors, endothelial cells, Agrin, glutathione-S-transferase T1, GBM, Protein kinase, CXCL9,11, IFN-g, glial cell-derived neutrophic factor. Have a role in AMR, detected by cell-based assays of endothelial cells (IF and Flow cytometry)

ABO Ags: on ALL cells.

Barrier to transplantation exception: -A2 (donors) - low A Ags & develop tolerance. -Rh present only on RBCs.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

sensitization of immune system occurs from

A
  • blood transfusions
  • pregnancy
  • prior transplants
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

panel reactive antibodies (PRA)

A
  • tells how sensitized a patient is to HLAs in general population
  • 0-100%
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

donor specific antibodies (DSA)

A
  • tests presence of Abs to DONOR’S HLA types only
  • semiquantitative
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

crossmatch

A
  • combines donor cells w/ recipient serum

crossmatch prediz oq? rejeicao hiperaguda

o crossmatch entre doador e receptor tem q ser negativo

rejeicao hiperaguda

Antibodies
Ab to the HLA molecules on the donor kidney

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

blood groups between donor and recipient must be

A

compatible (like blood transfusion)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

HLA matching has better outcomes if

A

match is 6/6

MHC mismatch is a risk for allograft (donor organ) rejection because peptide-binding regions of the MHCs are highly immunogenic.

Most immunogenic MHCs are A, B, and DR which are used as donor-recipient matching criteria for kidney transplantation.

HLA typing of donor and recipient determines

  • matching compatibility
  • range from 0/6 to 6/6
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

can rejection still occur if HLA match is 6/6? and, if yes, why?

A
  • yes!
  • non-HLA incompatibilities
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

contraindications to kidney transplantation

A
  • poor cardiac function
  • morbid obesity
  • psychosocial issues which can affect compliance
  • active infection
  • recent, unresolved cancer
  • ANY serious comorbidity which reduces life expectancy

Active infections
Active malignancy
Active psychiatric illness
Unacceptably high perioperative risk (unrevascularizable CAD)
High burden of comorbid conditions (dementia, end stage lung/heart disease)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

infections that need to be tested for in a transplant recipient

A
  • HBV
  • HCV
  • EBV
  • CMV
  • syphilis
  • HIV
  • latent TB
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

contraindications to living donation

A

absolutas

  • age < 18
  • GFR < 80 ml/min
  • hematuria/- proteinuria RELATIVA
  • HTN com lesao de orgao alvo
  • DM
  • obesity imc>35
  • neoplasia ativa
  • infectious disease ativa
  • significant, unresolved medical issues
  • psychosocial factors
  • inability to give informed consent

-nefrolitiase com possibilidade de recorrencia-citinuria, hiperoxaluria primaria , struvita

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

donor evaluation

A
  • H&P
  • CMP
  • FLP
  • GFR; 24 hour urine
  • UA, C+S
  • serum hCG
  • EKG
  • CXR
  • TTE
  • age-appropriate cancer screening
  • CT a/p
  • SW evaluation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

what cancer screening needs to done for transplant recipients?

A
  • mammogram
  • PAP smear
  • PSA
  • colonoscopy
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

waiting time after cancer treatment for most cancers before proceeding w/ transplant?

A

2 years

waiting time after cancer treatment for metastatic breast, colorectal, and melanoma before proceeding w/ transplant?5 years

waiting time after cancer treatment for non-melanoma skin cancer and some in situ malignancies before proceeding w/ transplant?

none, considered low risk

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

long term risk of ESRD over 15 years for kidney donor

A

6 fold increase

doadores tem maior risco de HAS, proteinuria, e falencia renal

risco de eskd = 1% apos 15 anos

se um doador precisar ir pra fila é prioridade

funcao renal reduz 30% apos doacao

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

minimum criteria for listing for kidney transplant

A
  • initiation of dialysis
  • GFR < 20 ml/min (time starts at time of eval and consent given to list)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

what is a nonstand kidney?

A
  • higher kidney donor profile index (KDPI) score (higher = worse)
  • cardiac death donor (longer CIT)
  • “higher-risk” donors
  • HBV and/or HCV donors
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

thymoglobulin MOA

A

depletes T cells

preparacao com anticorpos policlonais com grande numero de especificidade antigenica que incuem antigeno de superficie de linfocitos t e b, cels nk , plasmocitos e moleculas relacionadas a adesao celular

thymoglobulin adverse effects

  • leukopenia
  • thrombocytopenia
  • fever
  • flu-like symptoms
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

basiliximab MOA

A

blocks IL-2 receptors in T cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

CNI MOA

A

binds FK-binding protein thus inhibiting response to IL-2

CNI adverse effects

  • Afferent arteriole vasoconstriction
  • hyperkalemia
  • metabolic acidosis
  • hypomagnesemia
  • hyperglycemia and HLD by blocking beta cells in pancreas
  • renal fibrosis (long-term)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

azathioprine and MMF adverse effects

A
  • leukopenia
  • MMF can cause diarrhea

obs os niveis de aza e micofenolato nao se correlacionam bem com a toxicidade

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

use of azathioprine and allopurinol is

A

contraindicated

A combinação de azatioprina e alopurinol aumenta o risco de um indivíduo desenvolver mielotoxicidade grave. Se houver necessidade da prescrição do alopurinol, a dose da azatioprina deverá ser reduzida em dois terços. [carece de fontes] Além disso, contagens hematológicas deverão ser realizadas com freqüência.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

sirolimus MOA

A

mTOR inhibitor; blocks FK-binding protein thus inhibiting IL-2 response

adverse effect of sirolimus

  • poor wound healing
  • proteinuria
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

belatacept MOA

A

blocks accessory pathway of T cell stimulation

advantage of using belatacept avoid CNI nephrotoxicity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

perioperative complications

A
  • wound infection
  • bleeding
  • lymphocele
  • urine leak
  • transplant RAS
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

delayed graft function (DGF) histology

A

ATN

delayed graft function (DGF) risk factors

  • quality of donor kidney
  • kidney from after cardiac death donor
  • prolonged CIT
  • perioperative hypotension
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

how long to wait before renal transplant biopsy if DGF?

A

4 weeks

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

opportunistic infections
- first month

A

bacterial, perioperative

infeccao relacionada a cateter

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

opportunistic infections
- 2-6 months.

A

viral;

  • CMV
  • BK (polyoma) virus

sem profilaxia= pneumocistis , EBV herpes virus

hsv, vzv, ebv,cmv

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

opportunistic infections
- > 6 months

A

mostly bacterial

pnm, itu

cmv, aspergilos

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

infection ppx
- antifungal

A
  • fluconazole or nystatin x 1 month
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

infection ppx
- PJP

A
  • SMX/TMP or dapsone (if sulfa allergy) x 12 months
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

infection ppx
- CMV

A

depends on IgG serology

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

infection ppx

  • CMV positive donor
  • CMV negative recipient
A

valganciclovir x 6 months

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

infection ppx

  • CMV positive donor
  • CMV positive recipient
A

valganciclovir x 3 months

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

infection ppx

  • CMV negative donor
  • CMV negative recipient
A

low risk

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

CMV clinical manifestations

A
  • flu-like symptoms
  • leukopenia
  • diarrhea
  • colitis
  • rare; hepatitis, pneumonitis, ophthalmitis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

BK virus normally dormant in

A

urinary tract

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

subacute or chronic loss of allograft function d/t over IS

A

BK nephropathy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

treatment for BK nephropathy

A

taper down IS

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

uncommon clinical features of BK virus

A
  • hematuria
  • ureteral stricture
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

ddx of AKI in setting of transplant

A
  • same ddx as native kidneys (prerenal, renal, postrenal)
  • acute rejection
  • CNI toxicity
  • surgical complications (if soon after surgery) (urine leak, ureteral stenosis, transplant RAS)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

acute cellular rejection (ACR) histological findings

A

(in order of worsening severity)

  • T cell infiltrates
  • tubulitis
  • cellular involvement of larger blood vessels
  • hemorrhage

What is the three-signal model of T cell-mediated rejection?

  • Signal 1: Antigen triggers T-cell receptors and synapse formation occurs.
  • Signal 2: Signal 1 allows co-stimulation of antigen-presenting cells to occur.
  • Signal 3: Signal 1 and signal 2 stimulate a cascade of intracellular events culminating in the initiation of the T-cell cycle;

stimulation of the T-cell cycle allows T cells to infiltrate the graft. •

Summary effect is to inhibit T-cell receptor activation, cytokine production, and subsequent lymphocyte proliferation to prevent rejection.

T-Cell-Mediated Rejection. Cytotoxic T lymphocytes kill cell in grafted tissue → parenchymal and endothelial cells death → Thrombosis and graft ischemia → cytokines secrete CD4 + T cells → accumulation of lymphocyte and activate macrophages → Graft Destruction (Tubulointerstitial inflammation)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

antibody mediated rejection (AMR) histological findings

A

(in order of worsening severity)

  • PERItubular capillaritis
  • staining for C4d
  • duplication of endothelial BMs
  • positive DSA

Antibody directed against Graft MHC → activation of complement and recruitment of leukocytes → Vascular injury and endothelial damage → Thrombosis and ischemia → Graft Destruction.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

ACR treatment

A
  • pulse steroids
  • thymoglobulin if more severe
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

AMR treatment

A
  • plasmapheresis
  • IVIG
  • rituximab
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

treatment response to ACR

A

aggressive presentation, but may respond well

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

treatment response to AMR

A

often insidious onset and poor response if caught late

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

preformed DSA, although very rare, can lead to

A

hyperacute rejection

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

which type of rejection has better outcome?

A

ACR

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
51
Q

MC type of cancer post-transplant

A

squamous cell skin cancer

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
52
Q

rare cancer caused by EBV post-transplant

A

post-transplant lymphoproliferative disorder (PTLD)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
53
Q

post-transplant lymphoproliferative disorder (PTLD) risk factors

A
  • EBV negative recipients
  • greater intensity and duration IS
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
54
Q

treatment for post-transplant lymphoproliferative disorder (PTLD)

A
  • taper IS as tolerated
  • heme/onc
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
55
Q

MCC of death w/ functional graft

A

CVD

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
56
Q

CNIs inhibit metabolism of statins which leads to increased risk of

A

rhabdomyolysis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
57
Q

vaccines to AVOID post-transplant

A
  • avoid LIVE vaccines
  • varicella
  • INHALED influenza
  • MMR
  • meningococcal
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
58
Q

vaccines that should be received post-transplant

A
  • INJECTABLE influenza
  • pneumococcal
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
59
Q

does HPT improve after transplant?

A

yes, partially

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
60
Q

does fracture risk improve after transplant?

A

no

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
61
Q

does fracture risk improve post-transplant if steroids are tapered off?

A

no, they are still at increased risk compared to general population

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
62
Q

is infertility reversed after kidney transplant?

A

yes; should use contraception if not planning on conceiving

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
63
Q

risks to mother in pregnancy after transplantation

A
  • rejection
  • preeclampsia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
64
Q

risks to fetus in post-transplant mother

A
  • fetal loss
  • low birth weight
  • teratogens (MMF and sirolimus; must be stopped before pregnancy)
  • infection; CMV
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
65
Q

indication for pancreas transplant

A

hypoglycemic transplant

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
66
Q
  • usually occurs after rapid d/c’ing of IS
  • fatigue
  • fever
  • gross hematuria
  • allograft tenderness
A

graft intolerance syndrome

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
67
Q

treatment of graft intolerance syndrome

A

restart IS w/ higher dose steroids

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
68
Q

patients with bladder-drained pancreata develop

A

metabolic acidosis (loss of bicarb into bladder)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
69
Q

immunohistochemistry positive for SV40 (looks brown)

A

BK nephropathy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
70
Q

second line treatment for BK nephropathy after reduction of IS

A
  • IVIG
  • or leflunomide or cidofovir
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
71
Q

treatment for post-transplant erythrocytosis (PTE) (hb > 17 g/dl, hct > 51%)

A

ACEI

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
72
Q

which medication group can improve nephrotoxic effects of cyclosporine?

A

CCBs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
73
Q

biggest risk factor for post-transplant lymphoproliferative d/o with belatacept

A

EBV negative recipient

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
74
Q

sirolimus induced proteinuria will likely show up on biopsy as

A

podocytopathy causing FSGS

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
75
Q

ABO incompatible transplant is a/w

A

significantly higher risk of infection and hemorrhagic complications

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
76
Q

highest rate of recurrence post-transplant

A

diabetic nephropathy (40%)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
77
Q

second highest rate of recurrence post-transplant

A

FSGS (20-30%)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
78
Q
  • one of the MCC of allograft failure in early post-transplant period
  • sudden anuria
  • tenderness around allograft
A

early graft thrombosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
79
Q

HF before surgery with UF > 1.5-2 kg may be a strong predictor of

A

intraoperative hypotension

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
80
Q
  • progressively worsening HTN
  • unresponsive to meds
  • worsening renal function
  • recurrent flash pulmonary edema
A

transplant renal artery stenosis (TRAS)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
81
Q

transplant renal artery stenosis (TRAS) treatment

A

angiographic stenting

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
82
Q

IS medication that causes alopecia

A

tacrolimus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
83
Q

IS medication that causes hair growth and hirsutism

A

cyclosporine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
84
Q

how to diagnose CMV in a post-transplant patient with symptoms

A

serum CMV PCR

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
85
Q

does SLK have lower immunological risk for kidney rejection?

A

yes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
86
Q

medication used in treatment of resistant hypomagnesemia

A

amiloride

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
87
Q

treatment for lymphocele

A

laparoscopic peritoneal window creation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
88
Q

brown crap on immunohistochemistry in setting of AMR

A

C4D positivity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
89
Q

management of major surgery in post-transplant patient on sirolimus for IS

A
  • hold sirolimus x 5-10 days before surgery (wound healing)
  • add steroids if not already on any
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
90
Q

on histology, BK nephropathy mimics

A

ACR

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
91
Q

difference in nephrotoxicity between tacrolimus and cyclosporine

A

same, but tacrolimus is less nephrotoxic at lower doses

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
92
Q

what solution is infused during plasmapheresis? and is a possible adverse effect?

A
  • citrate for AC
  • hypocalcemia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
93
Q

expected post transplant survival (EPTS) score is based on which 4 factors?

A
  • age
  • DM
  • time on dialysis
  • previous solid organ transplant status
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
94
Q

what factors are a/w increased risk of PTLD?

A
  • recipient EBV negative
  • number of HLA mismatches (especially HLA-B or HLA-DR)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
95
Q

is BK shedding in urine (BK viruria) common?

A

yes, about 30%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
96
Q

donor risk of ESRD post-nephrectomy

A

8-10 fold increase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
97
Q

compensatory hypertrophy post-nephrectomy returns GFR to

A

75% of baseline at long-term f/u

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
98
Q

BK nephropathy initial test for diagnosis

A

serum BK PCR

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
99
Q

is weight or body fat composition different at 1 year in patients on steroids vs steroid-avoidance protocols?

A

no

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
100
Q

acute cellular rejection types
- 4 cells infiltrated per tubule AND TUBULITIS

A

type 1

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
101
Q

acute cellular rejection types
- > 10 cells infiltrated per tubule AND ENDOTHELIALITIS

A

type 2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
102
Q

acute cellular rejection types

  • lymphocytic cell infiltration AND interstitial hemorrhage
  • vasculitis
  • fibrinoid changes
A

type 3

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
103
Q

T cell activation cascade signals
- which medications block signal 1?

A
  • thymoglobulin
  • alemtuzumab
  • tacrolimus
  • cyclosporine
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
104
Q

T cell activation cascade signals
- which medications block signal 2?

A

belatacept

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
105
Q

T cell activation cascade signals
- which medications block signal 3?

A
  • basiliximab
  • sirolimus
  • everolimus
  • MMF
  • azathioprine
  • leflunomide
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
106
Q

treatment of ACR typically involves increasing which T cell activation cascade signal blockers?

A

signal 1 and 3

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
107
Q

medications that increase CSA levels (cyclosporine toxicity)

A

abx
- macrolides
# CCB
- verapamil
- diltiazem
# mTOR inhibitors
- sirolimus
- everolimus
#antifungals
- ketoconazole
- fluconazole

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
108
Q

what is the MOST appropriate INDUCTION IS?
- Caucasian recipients of two-haplotype-identical, living, related allograft

A

no induction required (low risk for rejection)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
109
Q

what is the MOST appropriate INDUCTION IS?

  • second transplant
  • sensitized recipients
  • transplant across ABO blood type
A

antithymocyte globulin (ATG)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
110
Q

what is the MOST appropriate INDUCTION IS?
- first line agent

A

basiliximab

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
111
Q

MMF MOA

A

inhibits inosine monophosphate dehydrogenase (IMPD), a key enzyme in purine synthesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
112
Q

azathioprine MOA

A
  • inhibits both DNA and RNA synthesis
  • also suppresses purine synthesis
  • action on cell cycle is not precisely defined
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
113
Q

which IS in a KTR should be avoided to prevent lowering sperm count?

A

mTOR inhibitors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
114
Q

MCC of anemia is a post-renal transplant patient

A

poor graft function

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
115
Q

histopathological finding that is an independent risk factor for anemia in a post-renal transplant patient

A

IFTA from prolonged CIT

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
116
Q

MOST strongly a/w new onset DM after kidney transplantation (NODAT)?

A

advanced recipient age

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
117
Q

relative risk of malignancy post-renal transplant
- NHL

A

40-50%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
118
Q

relative risk of malignancy post-renal transplant
- Kaposi’s sarcoma

A

400-500%

119
Q

relative risk of malignancy post-renal transplant
- SCC

A

15-20%

120
Q

relative risk of malignancy post-renal transplant
- melanoma

A

8-10%

121
Q

relative risk of malignancy post-renal transplant
- Ca of vulva/anus

A

100%

122
Q

highest ABSOLUTE risk of malignancy post-renal transplant

A

SCC

123
Q

BK polyoma viral infection progression is characterized by what stages?

A

urinary decoy cells –> viruria –> viremia –> BK nephropathy

124
Q

contraindicao para doar

A
  • uso de drogas ilicitas
  • dm
  • has -se bem controlada e sem lesao de orgao alvo depende
  • imc>30
    obs: receptores B (longo tempo de espera ) recebem enxerto de doador tipo A2 menos imunogenico)
125
Q

CMV

A
  • alta prevalencia na pop geral
  • é a principal infeccao viral no tx com diminuiçao da sobrevida do enxerto
  • maior risco= receptor igg negativo e doador igg positivo

seguido pelos receptores igg +

profilaxia com valganciclovir = cara

126
Q

drogas imunossupressoras

A

inibidores da calcineurina= tacrolimus e ciclosporina

sirolimus =inibidor da mtor

-imunoglobulina antitimocito= diversos efeitos colaterais ex- sindrome de liberacao de citocinas

basiliximabe= anticorpo monoclonal humanizado anti receptor IL2 usado na terapia de inducao em pacs c menor risco imunologico

uso de micofenolato associado a maior risco de infeccao por cmv

127
Q

azatioprina e gestacao

A

SEGURA

128
Q

Recorrencia glomerulopatia pos tx

A

glomerulopatias que mais recorrem =GESF, membranosa primaria, GNMP, mat mediada por complemento e glomerulopatia do c3

gesf primaria >30% geralmente no primeiro ano

GNMP tipo ii alta recorrencia mas baixa da tax a de perda do enxerto

gm= baixa recorrencia e é mais comum na forma “de novo”

nefrite lupica baixa recorrencia

129
Q

tacrolimo (FK) citocromo p450

drogas que induzem o citocromo p450= reduzem o nivel serico

A

reduzem o nivel =fenitoina e rifampicina

inibem o p450= aumentam os niveis= fluconazol, diltiazen e claritromicina

130
Q

rejeicao aguda

A

maioria nos primeiros 6 meses

apos 12 meses relacionada a má adesao ou reducao da imunossupressao

maioria assintomatica

rejeicao subclinica= alteracoes histologicas de rejeicao aguda na ausencia de elevacao da creat serica

incidencia de rejeicao subclinica depende perfil hla entre doador e receptor , presenca de dsa anticorpo antidoador especifico, protocolo d eimunossupressao e incidencia de funcao retardada do enxerto

131
Q

fatores de risco para rejeicao aguda

A

alto painel de ac contra a pop

tx previo

incompatibilidade abo

ma adesao ao tto

rejeicao previa

fc retardada do enxerto

cmv

tempo de isquemia prolongado

receptor afroamericano

PRA

mismatches hla

doador com idade avancada, doador com morte encefalica

132
Q

inibidores da calcineurina

A

CNIs remain a cornerstone of immunosuppressive regiments in kidney transplantation.

This class of drugs works by blocking calcineurin, an intricate protein in the signal transduction pathway that activates signal 3.

obs:Signal 3: Signal 1 and signal 2 stimulate a cascade of intracellular events culminating in the initiation of the T-cell cycle; stimulation of the T-cell cycle allows T cells to infiltrate the graft.

The two prototypes of the class are tacrolimus and cyclosporine, with tacrolimus being the primary drug of choice today.

The side effects of the CNIs include: • Nephrotoxicity • Thrombotic microangiopathy (TMA) • New onset diabetes after transplant • Hypertension • Tremor • Hypercalciuria, hyperkalemia, and hypomagnesemia • Alopecia (Tacrolimus,) • Hirsutism, gingival hyperplasia, hyperuricemia, metabolic acidosis, hypophosphatemia (Cyclosporine)

133
Q

fistula urinaria

A

a abordagem do pac é inicialmente conservadora e pode ser resolvida com aposicao do duplo j

nos casos de formacao de colecao de urina perienxerto =urinoma= confirma-se o diagnostico com analise do liquido com altas taxas de ureia e creat

134
Q

cmv

A

piora da funcao renal, dor abdominal, diarreia, elevacao de transaminases

uso de micofenolato

recebeu terapia antitimocito

135
Q

tacrolimus

A

ATRIV

principais causa de hipoaldosteronismo= ATR IV

nefropatia diabetica, aines, inibidores da calcineurina, espironolactona e anemia falciforme

136
Q

diagnostico de gesf na biopsia

A

biopsia comum 10 glomerulos e 2 arterias

para afastar GESF 25 glomerulos

137
Q

HTLV POSITIVO

A

contraindicacao absoluta

138
Q

biopsia mostrou= rejeicao aguda mediada por cels t banff 1b >25% de infiltrado tubulo intersticial I2 ou I3 + tubulite severa =T3

A

tto= pulso com metilprednisolona

139
Q

rejeicao cronica do enxerto

A

biopsia= espessamento de alcas capilares

proliferacao endocapilar

presença de fibrose e atrofia glomerular

imagem de duplo contorno na coloracao com prata metanamina

rejeição mediada por anticorpos.

140
Q
A
141
Q

tacrolimus e tremor

A

hiperglicemia e tremor

142
Q

anti hbc igg positivo

A

tx para receptores anti hbs positivo

143
Q

glomerulopatia do transplante

A

rejeicao mediada por anticorpos

fibrose e atrofia glomerular

achados semlhantes a GNMP= proliferacao endocapilar, espessamento de alças e duplo contorno

144
Q
A
145
Q

imunossupressore

A

corticoides =inibe a sintese de citocinas

ciclosporina e tacrolimus= inibem a calcineurina

sirolimus= inibe mtor

micofento = antiproliferativo que bloqueia a IMPDH e inibe a sintese de novo de purinas

146
Q

bkvirus = polioma virus

A

viruria assintomatica com ou sem viremia

estenose e obstrucao ureteral

nefrite intersticial

nefropatia por polioma

147
Q

céls dendriticas

A

apresentam antigenos as cels t cd4

que promovem lesao tecidual mediada por citocinas

tbm ativam linfocitos t citotoxicos e cels b

148
Q

lesao endotelial mediada pelo complemento

A

liberacao de fatores que ativam a cascata de coagulacao levando a formacao de microtrombos

149
Q

celulas T

A

podem mediar rejeicoes pela ativacao de macrofagos que desenvolvem a hipersensibilidade tardia

150
Q

aloanticorpos contra o doador

A

tem como alvo principal os antigenos do complexo principal de histocompatibilidade mhc ou em humanos hla

151
Q

cmv

A

PCR é uma importante arma diagnostica

entretanto o acomentimento do tgi e snc freuqentemente ocorre com pcr negativo e o diagnostico por biopsia é fundamental

152
Q

epstein barr

A

a maioria das dçs linfoproliferativas pós tx(PTLD) sao ligadas a infeccao por EBV

Maioria no primeiro ano, menos freq q tx de pulmao e coraçao

maior incidencia em crianca e inducao por timoglobulina

receptores ebv negativo com doador ebv positivo tem mais chance de desenvolver PTLD

manifestacoes clinicas: mononucleose like- febre, sudorese noturna, perda de peso, linfonodomegalias, sintomas do tgi e o envolvimento do snc pode estar presente em 1/3 dos pacs

biopsia fundamental para o diagnostico

tto=reduçao da imunossupressao e/ou rituximabe

qt= casos de apresentacao inicial grave

pior prognostico= doença tardia= apos 1 ano de tx

receptor ebv negativo

idade avancada

doença em mais de um sitio

monoclonalidade do tumor

uso de timoglobulina

ldh elevado

envolvimento do snc

153
Q

paraefeitos do tacrolimus

A

vasocontriccao, hiperuricemia, mat

154
Q

cmv

A

tto= ganciclovir venoso 14-21 dias

manter por 1 semana apos negativacao

dç invasiva 21-28 dias

profilaxia universal= uso de antiviral para pac de alto risco

tto preemptivo =monitorizacao semanal por pcr e tto acima de determinado valor

155
Q

cmv

A

PCR ou antigenemia

156
Q

necrose tubular aguda

A

tubulos dilatados e com vacuolizacao nao isomerica das cels

157
Q

DGF

funcao retardada do enxerto

A

tempo de isquemia fria aumenta o risco

inibidores da calcineurina tb podem causar

158
Q

tecnica cirurgica do tx

A

anastomose arterial usual é na arteria iliaca externa ou interna

anastomose ureteral pode ser uretero-ureteral ou uretero-vesical

159
Q

herpes zoster

A

drogas antiproliferativas micofenolato reduzir ou suspender

paciente imunossuprimido e lesao com mais de 3 dermatonos= aciclovir iv

160
Q

funcao retardada do enxerto

A

mat por inibidor de calcineurina e shu relacionada ao complemento =diagn diferencial

dgf tb pode estar no contexto de nta, nefrotoxicidade, infeccao, hipovolemia, linfocele, complicacoes vasculares e obstrucao do fluxo urinario

161
Q

drogas imunossupressoras

A

corticoide= intolerancia a glicose , has, ulceras gastricas, hiperlipidemia e osteoporose

micofenolato =diarreia, nauseas, dor abdomina, citopenias

tacrolimus=nefrotoxicidade aguda e cronica, has, dm

ciclosporina=hirsutismo, hiperplasia gengival,

azatiprina=mielotoxicidade

sirolimo=proteinuria, hiperlipidemia, pneumonite, citopenias

162
Q

nefrotoxicidade por inibidores da calcineurina

A

vasoconstriccao da art aferente

biopsia=hialinoseda arteria aferente ,vacuolizacao isomerica das celulas tubulares, fibrose tubulo intersticial

163
Q

fator de risco p dç cardiovasc

A

Considerando paciente com combinação de diversos fatores de risco para doença coronariana (> 60 anos, diabetes, hipertensão, dislipidemia e IC com fração de ejeção reduzida), deve-se realizar avaliação com cardiologista e estratificação invasiva com angiografia.

164
Q

dç oncologica curada

A

Não há contraindicação ao transplante no momento, pois a paciente tem antecedente de CA de mama com mais de 05 anos livre de doença. É importante uma avaliação detalhada do oncologista da paciente.

165
Q

nefrectomia do rim nativo

A

. Esta pode ser considerada em paciente com doença renal policística e rim volumoso que impeça o implante do enxerto; paciente com ITU de repetição, especialmente se associado a distúrbio urológico predisponente; pacientes com neoplasia renal e indicação de nefrectomia.

166
Q

doador criterio expandido

A

Doador de critério expandido é definido como qualquer doador com morte cerebral com idade > 60 anos ou um doador com idade > 50 anos e 2 das seguintes condições: hipertensão arterial, creatinina sérica terminal > ou = 1,5 mg/dl ou morte por acidente vascular cerebral.

Donors are older, may have more comorbidities (DM, HTM)
The kidneys wont last as long but they will work - better than no kidneys

167
Q

Imunohistoquímica mostrando marcação de C4d nos capilares peritubulares.

A
168
Q

critérios para rejeição aguda mediada por anticorpos.

A

O diagnóstico de rejeição aguda mediada por anticorpos é feito pela clínica + achados histológicos compatíveis + C4d nos capilares peritubulares + anticorpos anti-HLA específicos contra o doador.

Antibody mediated rejection

 Usually occurs in the first few weeks post transplant.
Pre sensitized pts are at high risk for AMR.

 Morphological features may be minimal. Tubular
injury may be the only manifestation

 Diffuse C4d staining is essential to diagnose AMR

 Donor recipient crossmatch or single antigent testing
should be performed to look for donor specific
antibodies

 Plasmapheresis + IVIg is the treatment of choice

169
Q

Infiltrado linfomononuclear nos túbulos (tubulite) e infiltrado intersticial.

A

Rejeição aguda mediada por células T.

170
Q

complicacoes precoces

A

Sangramento das anastomoses, trombose de veia renal, rejeição hiperaguda.

171
Q

sirolimus

efeitos colaterais

A

Proteinúria, dislipidemia, distúrbios de cicatrização

172
Q

neoplasia

A

Retirar paciente de lista de transplante; solicitar relatório do oncologista acerca da neoplasia e proposta terapêutica

173
Q

transplante renal prévio, painel de anticorpos de 90% e dificuldade de encontrar doador compatível.

A

avaliar protocolo de dessensibilização com plasmaférese e imunoglobulina.

174
Q

transfusão de 01 concentrado de hemácias.

A

Retirar paciente de lista de transplante temporariamente. Coletar novo painel em 15 dias e retornar à fila.

175
Q

trombose recoorente

A

Além da avaliação de rotina, fazer investigação de trombofilias / avaliação da hematologia.

176
Q

tacrolimus alopecia

A

ciclosporina hirsutismo

177
Q

HIPOMAGNESEMIA SECUNDARIA A TACROLIMUS

A

iniciar amilorida

178
Q

anemia e micofenolato

A

diminuir a dose do micofenolato para melhorar a anemia

179
Q

ERITROCITOSE POS TX HB>17

A

iniciar lisinopril

180
Q

tacrolimus

A

tremores cefaleia

Efeitos colaterais mais frequentes dos inibidores de calcineurina TACROLIMUS Renal

MAT , DM E ALOPECIA

Nefrotoxicidade

Acidose tubular renal tipo IV

Hipertensão arterial Resistência diurética Resistência diurética Hipercalemia Hipomagnesemia hipofosfatemia Gastrointesinal Diarréia Dor abdominal

181
Q

bk virus

A

Estenose ureteral, cistite hemorragicae nefropatia por bk vírus

Nefropatia do poliomavírus; As principais manifestações em transplante renal são nefrite intersticial e estenose ureteral.

A nefrite intersticial por poliomavírus se manifesta com quadro semelhante a rejeição aguda. O início da doença ocorre por volta do 10º ao 13º mês.

O paciente apresenta disfunção renal, podendo evoluir com perda progressiva da funcão do enxerto, e o sedimento urinário mostra alterações compatíveis com nefrite intersticial. A citologia urinária deve ser feita para a pesquisa de decoy cells. A biópsia com imunohistoquímica apresenta achados compatíveis com nefropatia por poliomavírus.

182
Q

aza +alopurinol

A

nao pode! neutropenia

obs= tacrolimus aumenta acido urico

183
Q

Rejeição mediada por anticorpos.

A

Painel elevado, doador falecido / morte encefálica, incompatibilidades HLA, transfusões prévias.

A ausência de C4d nos capilares peritubulares não descarta ocorrência de rejeição mediada por anticorpos.

184
Q

PCR CMV semanalmente pós transplante e, após 1 mês, apresentou dor abdominal e diarréia, associado a carga viral positiva = 5000 cópias/mL

A

Ganciclovir 5 mg/kg 12/12 horas.

Reduzir micofenolato ou trocar por sirolimus.

185
Q

nefrite intersticial por Polioma vírus

A

manifesta-se tipicamente nos primeiros 6 meses de transplante, estando associado a esquemas de imunossupressão mais intensos, podendo levar a insuficiência renal progressiva e necessidade de diálise.

. O padrão ouro para o diagnóstico é a biópsia renal, podendo ser realizado screening para Polioma vírus através de PCR na urina e no sangue.

O tratamento consiste na redução da imunossupressão.

186
Q

avaliacao doador vivo

A

Week 1:First appointment: risk/benefit assessment and discussionClinical/social/psychologic recipient evaluationRisks/benefits/expected outcomes

Discussion and selection of potential donorsLegal issuesIdentification of potential donors

Week 2:Immunogenetics: HLA tissue typing and crossmatchingWeek 3:Selection of the donor (based on HLA compatibility, age,family agreement)Week 4:Donor work-up (hematology/biochemistry/electrocardiography/imaging, all within the sameday

Week 5:Review of all clinical and laboratory donor evaluations

Week 6:Angiography/urography (with coronary evaluation fordonors50 years of age)

Review of donor/recipient and conditions; scheduletransplantation dateLegal documents sent 1 week before the transplantationdateRepeat cross-matching 1 week before transplantation

Hospital admission: the day before surgeryRepeat ABO compatibilityPreanesthetic evaluationRoutine hematologic evaluation/biochemistry/imagingand electrocardiography for donor and recipientTransplantation surgery

187
Q

nefrotoxicidade da ciclosporina pode ocorrer através de 2 formas:

A

Aguda: caracterizada pela piora rápida da função renal, níveis elevados de ciclosporina sanguínea e melhora com a correção da dose da medicação, sem maiores alterações histopatológicas e sedimento urinário sem alteração.

Esta forma é mais comum nos primeiros meses de transplante renal, quando os níveis sanguíneos e a dosagem são maiores

. Outra forma aguda é a síndrome hemolítico-urêmica (SHU), caracterizada por anemia microangiopática, podendo ser localizada ao rim ou associada à alteração de sistema nervoso central (SHU/PTT). anemia hemolítica, consumo de plaquetas, elevação de DHL que caracterizam a SHU.

Crônica: caracterizada pela piora progressiva da função renal, associada à hipertensão arterial, redução da filtração glomerular e aumento da resistência arteriolar.

maior chance de ocorrência com o tempo de transplante.

O sedimento urinário contém poucas alterações, sendo a mais comum, a ocorrência de proteinúria não-nefrótica.

Sindrome nefrótica é um evento raro, mas pode ocorrer.

Esta é a principal causa de alteração de função renal em pacientes transplantados cardíacos, sendo que alguns centros não realizam biópsia renal para pacientes com disfunção renal, a menos que existam evidências de outros diagnósticos para a nefropatia.

Causes afferent arteriolar vaso-constriction resulting in
reduced renal blood flow and GFR

 Allograft function improves if CNI toxicity is promptly
corrected

 Co-existent CNI toxicity and rejection can be present

 If creatinine does not improve, then look for other causes

 CNI toxicity presents with renal tubule vacuolization

188
Q

aumentam os niveis de inib calcineurinas

A

macrolideos

azois

DECREASE METABOLISM INCREASE CNI LEVELS Ketoconazole

Erythromycin Clarithromycin

Verapamil Diltiazem Nicardipine

189
Q

rejeicao aguda

A

mediada direta e indiretamente por cels t

clinicamente, rejeição aguda pode se manifestar com febre, dor e abaulamento na loja do enxerto, diminuição de volume urinário, além do aumento de creatinina, achado frequentemente tardio.

190
Q

has no tx

A

mto comum

associada a diminuicao da sobrevida do enxerto

rejeicao aguda e nefropatia cronica do enxerto

hipertensoa relacionada ao uso de inibidores da calcineurina

191
Q

pac grave

suspender a ciclosporina frente à possibilidade de NTA

A
192
Q

outras causas de microangiopatia após transplante renal.

A

SHU de novo, ou seja, aquela que se desenvolve em pacientes com outra doença primária, é problema raro no pós-transplante, exceto nos casos de toxicidade precoce por ciclosporina e nos casos de rejeição vascular aguda.

193
Q

Rejeição crônica mediada por células

A

O diagnóstico é confirmado pela biópsia renal, esperando-se encontrar um infiltrado inflamatório com tubulite (este é o principal alvo da agressão celular), acometimento intersticial e vascular.

194
Q

sirolimus rapamicina

A

Glomerulopatia da rapamicina: A rapamicina está associada a proteinúria e glomerulopatias (em particular a GESF).

Mecanismos possíveis para a proteinúria envolvem reabsorção tubular protéica diminuída, perda da regulação dos podócitos e aumento da expressão dos fatores de crescimento do endotélio vascular (VEGF) que alteram a permeabilidade da parede celular, levando a GESF.

Estudos retrospectivos em receptores renais que estavam em uso de rapamicina mostraram aumento da proteinúria já no 3º mês do uso da droga.

A proteinúria pode ser reversível após suspensão da droga. Morelon et al mostrou 64% de proteinuria em pacientes convertidos para a rapamicina. Além disso, GESF colapsante pode ser associada ao uso do sirolimus.

EFEITOS ADV

Pancytopenia

Hyperlipidemia

Edema

Insulin resistance

195
Q

transplante renal e alport

A

o transplante renal, no qual os pacientes com síndrome de Alport tipicamente têm excelentes desfechos, pois a doença não recorre no enxerto transplantado (já queo rim do doador teria uma MBG normal).

Entretanto, em aproximadamente 3% dos transplantados há evoluçãocom a doença do anticorpo antimembrana basal glomerular (direcionados principalmente contra a cadeia alfa-5 do colágeno tipo IV

196
Q

atr pos tx

A

No pós-transplante renal ATR pode ocorrer em até 33% dos pacientessendo suas principais causas: toxicidade por inibidores de calcineurina e rejeição aguda.]

A paciente não usava mais inibidores de calcineurina, mas sua doença de base era LES e a mesma apresentava hipocomplementemia. Portanto 2 fatores (rejeição e LES) justificariam lesão tubular proximal e distal, sendo então imprescindível a biópsia do enxerto renal. O laudo histológico foi: Nefrite Lúpica classe IV-S (A), sem características de rejeição. Vide algumas fotos de MO abaixo, IF (não mostrada) realizada com depósitos granulares difusos em alças de Igs e complemento.

197
Q

complicacoes precoces do tx

A

cirurgicas= sangramento, tromobse, fistula urinaria , obstrucao, linfocele

outras= ira, rejeciao aguda, mat,nta, ira pre renal (timoglobulina)

198
Q

efeitos colaterais iss

CORTICOIDES

A

Cataracts and Glaucoma/Cushing’s SyndromE/Osteoporosis

Immunosuppression/Hyperglycemi/Ulcers

Considerations

Adrenal Insufficiency

Taper Gradually

199
Q

EFEITOS COLATERAIS

CICLOSPORINA

A

/Nephrotoxicity/Hepatotoxicity//Infection

Hypertension/Hirsutism/Tremor/Hyperkalemia

Hypomagnesemia

Gingival Hyperplasia

HIPERLIPIDEMIA/HIPERURICEMIA/MAT/GOTA

CNIs have multiple toxicities including vasoconstriction, thrombotic microangiopathy, chronic interstitial fibrosis, alopecia, gingival hyperplasia, and new onset diabetes.

CNIs are known to increase cardiovascular morbidity and mortality and also have been implicated in causing chronic allograft nephropathy.

Considerations

Monitor Plasma Levels

Avoid Grapefruit Juice

Increased Risk of Lymphoma

200
Q
A
201
Q

efeitos adversos do tacrolimus

A

nefrotoxicidade, neutoxicidade

efeitos tgi

hipercalemia, hiperglicemia, hipertensao

infeccoes

202
Q

efeitos colaterais

azatioprina

A

supressao medular

aumenta toxicidade com uso de alopurinol

pancreatite

malignidade

203
Q

Basiliximab

A

Immunosuppressant drug

Used in transplant rejection prophylaxis

Mechanismmonoclonal antibody against Interleukin-2 (IL-2) receptors

Blocked IL-2 signalling impairs growth of all lymphocytes, leading to immunosuppression

Adverse Effects (low yield)

Edema /Hypertension/Tremor

204
Q

imunossupressao

A

Recommend starting combination immunosuppressive (IS) therapy before, or at the time of, transplant R except perhaps for transplantation between identical twins.

INDUCTION THERAPY

1) • Recommend a biologic agent as part of initial IS medication.
2) • Intended to improve the efficacy of immunosuppression by: • Reducing acute rejection, or • Allowing a reduction of other components of the regimen, such as calcineurin inhibitors (CNIs) or corticosteroids

. First-line induction therapy: recommend using an interleukin 2 receptor antagonist (IL2-RA). [R 1.2.1 (1B)] Induction therapy for high immunologic risk: recommend using lymphocyte-depleting agent. [R 1.2.2 (2B)]

205
Q

efeito colateral em comum = prednisona, mmf, rituximab,

A

linfopenia=

206
Q
A
207
Q

tacrolimus e fluconazol

A

O fluconazol pode aumentar as concentrações séricas de tacrolimo administrado por via oral em até 5 vezes por causa da inibição do metabolismo do tacrolimo pela CYP3A4 no intestino

208
Q

sangramento pós op tx

A

Bleeding
Early postop

 Stop Aspirin, Plavix and anticoagulants before
transplantation to minimize risk

 Correct uremia related platelet dysfunction and abnormal
Bleeding time through dialysis

 Early post op bleeding usually results from small hilar
vessels

 Close observation of vitals and HCT is crucial.

 Correct with blood products. Surgical exploration may be
necessary

209
Q

cel t -secretam IL com numeros q comecam com t e f

IL2 IL3 IL4 IL5 IL10

Two, Three, Four, Five, Ten.

IL-2, IL-3 are secreted by all T cells.

IL-4, IL-5, IL-10 are predominantly secreted by TH2 cells.

So what do TH1 cells secrete? IFN-Y.

If you flatten the arms of Y it does look like a T and it’s also got a F!

A
210
Q

Vascular thrombosis

A

 Abrupt cessation of urine output +/- graft pain &
swelling and raised creatinine raises suspicion

 Most arterial and venous thrombosis happen within
the first few days of transplantation.

 Reported incidence - Arterial (1%) Venous (1-4%)

 Risk increased in patients with atherosclerotic
vessels, anti-cardiolipin abs, prior thrombotic
tendencies and thrombocythemia

 Early diagnosis is crucial in salvaging grafts. Obtain
doppler US or isotope renal scan asa

Resistive index

 Normal RI
0.6 – 0.8

 Elevated
RI
>0.9

211
Q

trombose vascular prevencao

A

Prevention through early anticoagulation in high
risk pts

 Acute arterial thrombosis is usually due to
technical problem or small embolus

 Venous thrombosis may present with gross
hematuria

 Surgical repair should be carried out immediately

 Late thrombosis (upto 2 months) is mostly from
rejection

212
Q

rejeicao hiperaguda

A 
Results from circulating preformed cytotoxic
antidonor antibodies directed to ABO antigens or
donor HLA class I antigens

 Antibodies cause complement mediated endothelial
injury, plt aggregation and microvascular thrombosis

 Highly sensitized patients are at most risk

 Very rare occurrence nowadays due to improved pre
transplant crossmatch techniques

 Results in allograft failure and nephrectomy

213
Q

Post transplant Acute tubular necrosis

A

About 20-40% incidence among cadaveric organ
transplants. Can last for one to several weeks.

 Incidence depends on age, quality of the donor
kidney, cold & warm ischemia time, circumstances of
death, early use of CNI etc.

 Rule out other causes of delayed graft function such
as obstruction and vascular causes by US and acute
rejection by biopsy within 7-10 days

 Cautious use of CNI. Take care to avoid hypotensive
injury to allograft on dialysis

214
Q

Post Transplant TMA

A

Anemia, Thromobocytopenia, Raising LDH,
Schisotocytes on peripheral smear should raise
suspicion

 Can be localized to kidney or can present as HUS

 Diagnosed by glomerular microthrombi on biopsy.
C4d stain should be done to rule out AMR

 Initial biopsy may be negative, hence high index of
suspicion is needed.

 Both cyclosporin and tacrolimus can cause TMA.
Early discontinuation or reduction of CNI with
plasmapheresis may help prevent graft loss

215
Q

colecoes no usg renal

A

Differential diagnosis:
 Lymphocele
 Urinary leak (urinoma)
 Urinary obstruction
 Acute rejection

 Percutaneous aspirate and send fluid for
microscopy, culture, protein and creatinine
estimation

216
Q

linfocele

A

Result from severed lymphatic vessels that
overlie iliac vessels. Usually presents within
weeks

 Even small lymphocele can occasionally result in
ureteral obstruction

 Large lymphoceles can present as abdominal
mass, incontinence, scrotal masses or vena caval
obstruction

 Sonolucent fluid collection with septations on US

Early Sirolimus use increase the incidence from 18%
to 38%

 Fluid is clear with high protein content and creatinine
concentration similar to serum

 Treatment
 Small – No intervention

 Large lymphocele with compression

External drainage
Sclerosing agents
Marsupialization

217
Q

vazamento de urina

A

Confirm fluid collection with US or CT. Nuclear
studies or retrograde cystogram may be beneficial

 Send aspirate for creatinine estimation. Immediate
provide bladder rest with foley

 Percut nephrostomy and nephrogram will be definitive
and also help with management

 Type of surgical repair depends on the level of leak
and viability of the transplant ureter

218
Q

obstrucao ureteral

A

Manifests with elevated creatinine

 Low grade pelvi-calyceal dilatation of transplant
kidney is normal. However increasing hydronephrosis
is suggestive of obstruction

 Mag 3 scan may be helpful to diagnosis this condition
(least intervention with no nephrotoxicity)

 Percutaneous antegrade pyelography is the best
diagnostic modality to diagnose the level of
obstruction

Ureteral obstruction

 Early post-op obstruction is due to blood clots,
technical failed ureteric reimplantation and ureteral
slough.
 Intrinsic obstruction results from ureteric stenosis
 Extrinsic compression results from Lymphocele,
ureteral kinking
 Late causes include calculi

 Treatment:
 Percutaneous nephrostomy with ureteral stent
(most cases)
 Surgical repair

219
Q

RAMA

A

Microscopia Óptica

BIÓPSIA NO TEMPO ZERO: Rim com glomérulos preservados, presença de necrose tubular aguda. Artérias não vizualizadas. Foram vistas somente arteríolas que não mostraram alterações histológicas.

Necrose Tubular Aguda- Tempo Zero

BIÓPSIA NO 17º PO: Persistência de necrose tubular aguda, agora em regeneração. Dois glomérulos mostraram-se isquêmicos. Nesta biópsia evidenciou-se arteríoloesclerose hialina. Artérias não evidenciadas também nesta biópsia. Atrofia e fibrose intersticiais em cerca e 5% do material examinado. Ausência de infiltrado inflamatório caracterizando rejeição.

NTA em regeneração com arteríoloesclerose hialina e glomérulo hialinizado

BIÓPSIA NO 32º PO: Sem alteração da intensidade de fibrose e atrofia tubular. Ausência de infiltrado inflamatório caracterizando rejeição aguda. Glomérulos sem alterações.Evidenciada artéria interlobular com proliferação fibrointimal, carcterizada por proliferação de miocitos e ruptura de membrana elástica interna duplicada ao PAMS.

Proliferação intimal com miocitos evidentes

C4d positivo em mais do que 50% dos capilares peritubulares
através de técnica de imunofluorescência indireta.

Conclusão diagnóstica: Os achados de Necrose Tubular Aguda, C4d positivo em capilares peritubulares e “cross match” positivo, apontam para o diagnóstico de Rejeição Aguda Mediada por Anticorpo.

Patologista: Dra. Daisa Ribeiro David, Unidade de Transplante Renal do HCFMUSP.

DISCUSSÃO:

Nefrite intersticial aguda
Esta é sempre uma causa de IRA a ser pensada, apesar da baixa freqüência. A paciente recebeu cefazolina profilática na primeira semana após o transplante (dado não apresentado), além da furosemida e omeprazol – todas drogas que podem causar NIA. Há de se considerar inclusive os atuais imunossupressores. Ela também não apresentou nenhum dos elementos clássicos: febre, eosinofilia, rash – presentes em apenas uma minoria dos casos. Falando contra NIA, a presença de um sedimento urinário pobre. A pesquisa de eosinófilos na urina não foi realizada e, conforme citação, seu papel no diagnóstico ainda é incerto.

Pielonefrite aguda
A urocultura positiva, mesmo que apenas 30.000 UFC/mL, falava a favor deste diagnóstico. Não havia febre, hematúria ou piúria, nem dor a palpação do enxerto. O hemograma não tinha alterações na série branca que sugerisse quadro infeccioso. A repetição dos exames de urina I e urocultura, com negativação desta última, além da normalização da PCR logo em seguida, mesmo sem antibiótico, fez com que excluíssemos esta possibilidade.

Rejeição Celular Aguda (RCA)
Esta era a primeira hipótese a ser pensada, excluídas causas pré e pós-renais, mesmo não havendo dor em local do enxerto, eosinofilia, mialgia, febre, piora da hipertensão, ganho ponderal e oligúria. Deve ser pensada em todo caso de IRA pós-transplante. Define-se rejeição aguda ao aloenxerto renal como uma piora da função associada com alterações histológicas específicas. A RCA é um processo não mediado por anticorpo. A classificação de Banff 97 é uma padronização dos aspectos histológicos de biópsias de rins transplantados. Ela classifica a rejeição aguda da seguinte forma: I) Rejeição tubulointersticial sem arterite, dividida em IA = presença de tubulite moderada e IB = tubulite severa; II) Rejeição vascular, caracterizada por arterite intimal, subdivida em IIA = leve a moderada e IIB = severa; III) Rejeição grave com arterite transmural, com ou sem necrose fibrinóide ou da musculatura lisa. Nos casos de rejeição celular, em geral, não há deposição do C4d. Quando há apenas tubulite leve e/ou inflamação intersticial focal categoriza-se como “alterações limítrofes”. A rejeição celular aguda geralmente ocorre entre o 7º e o 30º dia pós-transplante, podendo ocorrer até mesmo anos depois. Representava até 90% das rejeições precoces evidenciadas por biópsia. Esta paciente possuía alguns fatores de risco para RCA: presença de 5 em 6 incompatibilidades no HLA, necrose tubular aguda, rim de doador marginal, reatividade contra painel >50%. Outros fatores de risco para RCA são: função retardada do enxerto, retransplante, baixa dose de imunossupressores, baixa aderência. A chance de ocorrer RCA está relacionada com a terapia imunossupressora, sendo que esquemas mais potentes como os utilizados hoje atingem taxas menores do que 15% no primeiro ano de transplante.

Rim histologicamente normal
Neste item entrariam as causas pré e talvez pós-renais de IRA. Apesar da diarréia, faltaram sinais de hipovolemia, como hipotensão postural. E mesmo após a reposição volêmica parenteral, a creatinina continuou a ascender, tornando menos provável a hipótese de puramente pré-renal (sem NTA). As causas pós-renais, sejam coleções não visualizadas ao US, estenose ou torção de ureter, fístula, entre outras, eram todas possíveis. Lembrar que a paciente ainda tinha diurese residual dos rins primitivos. No entanto, a biópsia não demonstrou dilatação do sistema coletor ou edema intersticial, achados mais esperados para obstrução, nem o US subseqüente teve indício de causa pós-renal. Por fim, outra hipótese prevaleceu.

Rejeição Aguda Mediada por Anticorpo (RAMA)
As atuais terapias para prevenir ou tratar a rejeição, incluindo anticorpos anticélulas-T, inibidores de calcineurina, micofenolato, sirolimus e prednisona, têm como alvo o linfócito T. Foram elas que aumentaram a sobrevida do enxerto em até 88-95% no primeiro ano. No entanto, episódios de rejeição aguda ainda acontecem, e está cada vez mais evidente a participação de anticorpos nestes processos (a chamada “rejeição humoral”).
A identificação do C4d na biópsia renal é uma ferramenta importante no entendimento da resposta aloimune e, em particular, no diagnóstico de RAMA. O C4d é um dos produtos da quebra do C4 pela via clássica do complemento. Tem como característica a capacidade de ligação covalente com a membrana basal endotelial e colágeno, reduzindo a sua chance de remoção e aumentando a possibilidade de servir como uma “pista imunológica” da ativação de complemento e atividade dos anticorpos.
A RAMA ocorre pela presença de anticorpos contra o HLA do doador, antígenos do sistema ABO ou outros componentes mais recentemente identificados (endotélio, MICA, vimentina, receptor de angiotensina II). Os anti-HLA podem ser identificados pela prova cruzada. No caso do teste da reatividade contra painel, a percentagem de reatividade indica o grau de sensibilização àquele pool de antígenos, e quanto mais alto maior a chance de rejeição. Normalmente fazemos o painel por técnica de Elisa. O grau de sensibilização desta paciente era considerado alto, e possivelmente devido às transfusões de sangue recebidas no passado. Na prova-cruzada (PC), são utilizados os linfócitos T e B do doador, sendo considerados doador-específicos (diferente do painel). A positividade da PC para células-T sugere anticorpos classe I específicos ao doador, sendo uma contra-indicação absoluta ao transplante. Já uma PC positiva para células-B com reação negativa para célula-T pode indicar baixos títulos de anticorpo classe I (existentes mas não detectados pelo método) e presença de anticorpo classe II ou autoanticorpos/anticorpos não-HLA, e seu efeito no transplante é determinado de acordo com o caso específico. A paciente apresentada tinha prova cruzada por CDC negativa para linfócitos T e B, e assim permanecendo em todos os momentos. No entanto, quando realizada por técnica mais sensível num segundo momento (após a primeira biópsia, utilizando soro histórico), no caso por citometria de fluxo (FACS), tanto o soro pré-transplante do receptor quanto os subseqüentes eram positivos para linfócitos B; para linfócitos T a prova ficou positiva após o transplante, negativando depois com o tratamento. Isso indica provavelmente a presença de anticorpos pré-formadas em baixos títulos, talvez devido as transfusões, não detectados pelas técnicas habituais, e que aumentaram com a nova exposição aos antígenos do aloenxerto.

Os atuais critérios diagnósticos para RAMA são:
1. Evidência morfológica: neutrófilos e/ou monócitos/macrófagos em capilares peritubulares e/ou glomerulite; necrose fibrinóide arterial ou trombo em capilares glomerulares, arteríolas e/ou pequenas artérias; lesão tubular aguda.
2. Evidência imuno-histológica: deposição de C4d em capilares peritubulares; imunoglobulina e/ou complemento na necrose fibrinóide.
3. Evidência sorológica: anticorpos circulantes contra o HLA do doador ou outro anticorpo antidoador no momento da biópsia.
Ao menos um item de cada uma das três categorias acima deve estar presente para o diagnóstico de RAMA. Pelo NIH (National Institutes of Health), há também necessidade de haver disfunção renal. Observação: uma pequena porção dos casos de RAMA (<10%) demonstra apenas lesão tubular aguda como alteração morfológica.
O tratamento inclui a utilização de imunoglobulina – IVIG ou imunoglobulina anti-CMV, plasmaférese, troca da imunossupressão para esquema contendo MMF e FK. A realização da plasmaférese parece ser superior ao uso de imunoglobulina em dose alta isolada, e o número de sessões depende da negativação da PC (em geral 6 a 9 sessões). O rituximab parece conferir também benefício adicional. O uso de ATG junto ao esquema deve ser considerado principalmente nos casos com histologia parecida com RCA.

Evolução do caso:
A primeira biópsia foi realizada numa sexta-feira, 23/6, e no mesmo dia foi iniciada pulsoterapia com metilprednisolona 500mg/dia, por 3 dias, pela suspeita de rejeição celular aguda. Na terça-feira seguinte, com o resultado de NTA e presença de C4d 3+ na biópsia, a hipótese de RAMA também foi considerada. Nesse momento foram coletadas novas amostras para prova cruzada em busca de evidência sorológica e iniciada imunoglobulina humana (IVIG) na dose de 2g/kg em 2 dias. A técnica utilizada para as novas provas cruzadas, incluindo soro histórico, foi a citometria de fluxo (FACS), que resultou positiva para linfócitos B (mesmo a amostra pré-trasplante). A PC por FACS para linfócitos-T tornou-se positiva no pós-transplante, chegando a altos títulos. Uma segunda biópsia foi realizada, seguida de 8 sessões de plasmaférese, até a negativação do crossmatch (por FACS) para linfócitos T. A melhora da função renal acompanhou tal tratamento, sendo que após a última plasmaférese a creatinina atingiu o valor de 1,5 e dois meses após o transplante estava 1,2 (consulta ambulatorial).

220
Q

Early Renal allograft rejection

A

Hyperacute rejection (within minutes to hours)

 Accelerated acute rejection (within first week of
transplant)

 Acute cellular rejection

 Acute humoral or antibody mediated rejection

221
Q

Accelerated acute rejection

A

Similar mechanism of allograft injury like hyper acute
rejection but happens within a week

 Raised creatinine, anuria or oliguria +/- graft tenderness
and fever

 Allograft biopsy shows massive infiltration of
lymphocytes, plasma cells and macrophages

 Immediate treatment with anti-T cell antibody with IV
pulse steroids may help save upto 50% of the allografts

222
Q

rejeicao celular aguda

A

T cell mediated injury against renal tubules
Most common type of rejection
 Incidence is upto 15% within 1 year and usually happens within first 3 months
 >95% are reversible

Treatment
 Mild: pulse IV steroids
Moderate & Severe: Anti T cell therapy+ steroids

 Recurrent rejections or late ACR adversely affects graft outcome

Rejeição Celular Aguda (RCA)
Esta era a primeira hipótese a ser pensada, excluídas causas pré e pós-renais, mesmo não havendo dor em local do enxerto, eosinofilia, mialgia, febre, piora da hipertensão, ganho ponderal e oligúria.

Deve ser pensada em todo caso de IRA pós-transplante.

Define-se rejeição aguda ao aloenxerto renal como uma piora da função associada com alterações histológicas específicas.

A RCA é um processo não mediado por anticorpo. A classificação de Banff 97 é uma padronização dos aspectos histológicos de biópsias de rins transplantados

. Ela classifica a rejeição aguda da seguinte forma:

I) Rejeição tubulointersticial sem arterite, dividida em IA = presença de tubulite moderada e IB = tubulite severa;

II) Rejeição vascular, caracterizada por arterite intimal, subdivida em IIA = leve a moderada e IIB = severa;

III) Rejeição grave com arterite transmural, com ou sem necrose fibrinóide ou da musculatura lisa.

Nos casos de rejeição celular, em geral, não há deposição do C4d. Quando há apenas tubulite leve e/ou inflamação intersticial focal categoriza-se como “alterações limítrofes”.

A rejeição celular aguda geralmente ocorre entre o 7º e o 30º dia pós-transplante, podendo ocorrer até mesmo anos depois. Representava até 90% das rejeições precoces evidenciadas por biópsia. Esta paciente possuía alguns fatores de risco para RCA: presença de 5 em 6 incompatibilidades no HLA, necrose tubular aguda, rim de doador marginal, reatividade contra painel >50%. Outros fatores de risco para RCA são: função retardada do enxerto, retransplante, baixa dose de imunossupressores, baixa aderência. A chance de ocorrer RCA está relacionada com a terapia imunossupressora, sendo que esquemas mais potentes como os utilizados hoje atingem taxas menores do que 15% no primeiro ano de transplante.

223
Q

peritubular cd4 deposition

A
224
Q

acute x cronic rejection

A
225
Q

Recurrent renal disease post tx

A

Primary Renal Disease

 FSGS
 MPGN I & II
 IgA Nephropathy
 Anti-GBM disease

226
Q

recurrent sistemic disease

A

B. Systemic Diseases

 Primary Oxalosis
 SLE
 HUS
 DM
 Cystinosis
 ANCA, Anti-GBM

 HSP
 Amyloidosis
 Mixed
cryoglobulinemia
 Alports
 Sickle cell
 Fabry’s disease

227
Q

infeccoes pos tx

A

precoce= 0-30 dias

nosocomiais

relacionadas ao doador:hcv, micose

receptor=influenza, aspergilus,pseudomonas

228
Q

Absolute Contraindications to Kidney TransplantationRelative Contraindications

Active medication noncompliance

Active malignancy

Active infection

Active substance abuse

Uncontrolled psychiatric disorder

Severe bilateral iliac or lower-extremity arterial disease

A

Relative Contraindication

Active systemic diseases (e.g. SLE, ANCA

Uncontrolled tertiary hyperPTH (parathyroidectomy first)

Primary oxalosis (refer to combined kidney-liver)

Systemic amyloidosis, especially with cardiac involvement

Early failure of prior transplant due to recurrent disease

Severe ischemic cardiomyopathy with EF<30%

229
Q

testes

A

With regard to testing, human leukocyte antigen (HLA) alleles should be identified for each candidate. HLA-A, HLA-B, HLA-DR alleles (2 alleles for each) are used for antigen mismatch scoring (between 0-6) which is a main determinant of prioritization in organ offering. In addition, preformed antibodies against specific HLAs should be tested at initial evaluation and then periodically as it is a key risk factor for antibody-mediated rejection. Commonly performed other tests are summarized in

230
Q

avaliacao receptor

A
231
Q

sistema imune

A

consists of mainly two subdivisions: innate (natural) and adaptive (humoral) immunity.

Innate immunity is non-specific and has no memory. It is the first-line protection against foreign antigens.

Adaptive immunity is antigen-specific and has memory function.

Cytokines are

crucial for development and differentiation for immune cells. Both type of immunities can activate each other and play role in transplant rejection.

For example, ischemia-reperfusion injury during transplantation can cause expression of damage-associated molecular patterns (DAMPs) and activate innate system which cause further tissue damage and release of donor antigens. This process may result in allorecognition by B and/or T lymphocytes and subsequent allograft rejection. Similarly, allograft rejection risk increases in sepsis or infection.

232
Q

Cells of Innate Immunity

A

Local macrophages or dendritic cells: Both drives from monocytes. They produce the first response to foreign antigens by phagocytosis and attracts neutrophils. Dendritic cells remain local and are the most important APCs. Hence, they have a crucial role in allograft rejection. They phagocyte donor antigens and present to T-cells in lymphoid organs.

Neutrophils: They damage microorganisms and infected cells. They don’t have antigen presenting abilities.

Natural Killer (NK) cells: They kill the viral infected cells and tumor cells. Their killing function does not need priming by APCs. Absence of MHC-1 molecule is a signal for NK cell-induced death (which may occur in tumor cells or stressed cells) which is called “Self-missing hypothesis”.

Other cell types include eosinophils (anti-parasitic actions), basophils / mast cell (allergic reactions, anti-helminthic) and epithelial cells.

233
Q

cels do sist imune adaptativo

A

T and B lymphocytes are main adaptive immune cells.

They develop into self-tolerant status in the central lymphoid organs including thymus (T lymphocytes) and bone marrow (B-cells) and then migrate into peripheral lymphoid organs including lymph nodes and spleen.

B-cells: Naïve B-cells has IgD on their surface which recognize alloantigens and undergo class switching (switch into IgG/IgE/IgA/IgM) to become a memory B-cell. This process also requires T-helper cells (Th).

T cells: Naïve T cells differentiate into either helper T-cell (CD4+) or cytotoxic T-cell (CD8+) in the thymus. All T-cells have T-cell receptor (TCR) and require antigen presentation by APCs to develop into memory cells. For this interaction, two signals are required: Signal 1 and signal 2 (co-stimulation). Signal 1 is the binding of TCR to MHC-antigen complex. Signal 2 is the binding of other surface molecules for activating or inhibitory co-stimulation (Figure-1).

Cytotoxic T-cells: Naïve CD8 T-cells maturate into memory T-cells in the peripheral lymphoid organs when their TCR binds to MHC-I / antigen complex on APCs. Then, they migrate into the end-organ (allograft) and induce apoptosis of target cells by perforin/granzyme B transfer or Fas/Fas ligand binding.

T-helper (Th) cells: There are various subtypes of T-helper cells. All of them carry CD4 molecule. Naïve CD4 cells recognize antigens in the secondary lymphoid organs when their TCR binds to MHC-II / antigen complex on APCs and differentiate into specific T-helper cells. Th1 cells activates cytotoxic T-cells and macrophages with IL-2 and IFN . Th-2 and follicular Th cells interact with B-cells and induce memory B-cell formation. Regulatory T cells (Treg) suppress the immune response and maintain self-tolerance which is important to prevent autoimmunity and transplant rejection.

234
Q

rejeicao mediada por anticorpo

Os achados de Necrose Tubular Aguda, C4d positivo em capilares peritubulares e “cross match” positivo, apontam para o diagnóstico de Rejeição Aguda Mediada por Anticorpo.

A

As atuais terapias para prevenir ou tratar a rejeição, incluindo anticorpos anticélulas-T, inibidores de calcineurina, micofenolato, sirolimus e prednisona, têm como alvo o linfócito T.

Foram elas que aumentaram a sobrevida do enxerto em até 88-95% no primeiro ano.

No entanto, episódios de rejeição aguda ainda acontecem, e está cada vez mais evidente a participação de anticorpos nestes processos (a chamada “rejeição humoral”).

A identificação do C4d na biópsia renal é uma ferramenta importante no entendimento da resposta aloimune e, em particular, no diagnóstico de RAMA. O C4d é um dos produtos da quebra do C4 pela via clássica do complemento. Tem como característica a capacidade de ligação covalente com a membrana basal endotelial e colágeno, reduzindo a sua chance de remoção e aumentando a possibilidade de servir como uma “pista imunológica” da ativação de complemento e atividade dos anticorpos.

A RAMA ocorre pela presença de anticorpos contra o HLA do doador, antígenos do sistema ABO ou outros componentes mais recentemente identificados (endotélio, MICA, vimentina, receptor de angiotensina II).

Os anti-HLA podem ser identificados pela prova cruzada. No caso do teste da reatividade contra painel, a percentagem de reatividade indica o grau de sensibilização àquele pool de antígenos, e quanto mais alto maior a chance de rejeição. Normalmente fazemos o painel por técnica de Elisa.

. Na prova-cruzada (PC), são utilizados os linfócitos T e B do doador, sendo considerados doador-específicos (diferente do painel). A positividade da PC para células-T sugere anticorpos classe I específicos ao doador, sendo uma contra-indicação absoluta ao transplante.

Já uma PC positiva para células-B com reação negativa para célula-T pode indicar baixos títulos de anticorpo classe I (existentes mas não detectados pelo método) e presença de anticorpo classe II ou autoanticorpos/anticorpos não-HLA, e seu efeito no transplante é determinado de acordo com o caso específico.

A paciente apresentada tinha prova cruzada por CDC negativa para linfócitos T e B, e assim permanecendo em todos os momentos. No entanto, quando realizada por técnica mais sensível num segundo momento (após a primeira biópsia, utilizando soro histórico), no caso por citometria de fluxo (FACS), tanto o soro pré-transplante do receptor quanto os subseqüentes eram positivos para linfócitos B; para linfócitos T a prova ficou positiva após o transplante, negativando depois com o tratamento. Isso indica provavelmente a presença de anticorpos pré-formadas em baixos títulos, talvez devido as transfusões, não detectados pelas técnicas habituais, e que aumentaram com a nova exposição aos antígenos do aloenxerto.

Os atuais critérios diagnósticos para RAMA são:
1. Evidência morfológica: neutrófilos e/ou monócitos/macrófagos em capilares peritubulares e/ou glomerulite; necrose fibrinóide arterial ou trombo em capilares glomerulares, arteríolas e/ou pequenas artérias; lesão tubular aguda.
2. Evidência imuno-histológica: deposição de C4d em capilares peritubulares; imunoglobulina e/ou complemento na necrose fibrinóide.
3. Evidência sorológica: anticorpos circulantes contra o HLA do doador ou outro anticorpo antidoador no momento da biópsia.
Ao menos um item de cada uma das três categorias acima deve estar presente para o diagnóstico de RAMA. Pelo NIH (National Institutes of Health), há também necessidade de haver disfunção renal. Observação: uma pequena porção dos casos de RAMA (<10%) demonstra apenas lesão tubular aguda como alteração morfológica.
O tratamento inclui a utilização de imunoglobulina – IVIG ou imunoglobulina anti-CMV, plasmaférese, troca da imunossupressão para esquema contendo MMF e FK. A realização da plasmaférese parece ser superior ao uso de imunoglobulina em dose alta isolada, e o número de sessões depende da negativação da PC (em geral 6 a 9 sessões). O rituximab parece conferir também benefício adicional. O uso de ATG junto ao esquema deve ser considerado principalmente nos casos com histologia parecida com RCA.

Evolução do caso:
A primeira biópsia foi realizada numa sexta-feira, 23/6, e no mesmo dia foi iniciada pulsoterapia com metilprednisolona 500mg/dia, por 3 dias, pela suspeita de rejeição celular aguda. Na terça-feira seguinte, com o resultado de NTA e presença de C4d 3+ na biópsia, a hipótese de RAMA também foi considerada. Nesse momento foram coletadas novas amostras para prova cruzada em busca de evidência sorológica e iniciada imunoglobulina humana (IVIG) na dose de 2g/kg em 2 dias. A técnica utilizada para as novas provas cruzadas, incluindo soro histórico, foi a citometria de fluxo (FACS), que resultou positiva para linfócitos B (mesmo a amostra pré-trasplante). A PC por FACS para linfócitos-T tornou-se positiva no pós-transplante, chegando a altos títulos. Uma segunda biópsia foi realizada, seguida de 8 sessões de plasmaférese, até a negativação do crossmatch (por FACS) para linfócitos T. A melhora da função renal acompanhou tal tratamento, sendo que após a última plasmaférese a creatinina atingiu o valor de 1,5 e dois meses após o transplante estava 1,2 (consulta ambulatorial).

235
Q

como a rejeicao ocorre

A

Donor’s MHC molecules are very immunogenic and are the main antigen responsible from rejection.

They are captured by donor’s or recipient’s APCs and carried into the lymphoid organs.

APCs present the processed antigen to cytotoxic or helper T-cells. This antigen presentation stimulates naïve T-cells to develop into memory T-cells.

They migrate into graft tissue as well as secrete cytokines to recruit other inflammatory cells like macrophages to cause acute cellular rejection.

Moreover, Soluble alloantigens are captured by naïve B-cells in the peripheral lymphoid organs. This induces class switching and memory B-cell formation. Memory B-cells secrete antibodies against donor’s antigens (mainly anti- MHC antibodies). Secreted antibodies opsonize the graft cells.

Finally, cells with antibody-dependent cellular cytotoxicity capability (NK cells, macrophages, neutrophils, and eosinophils) and complement system attack the opsonized cells. That process causes antibody mediated rejection (Figure-2).

236
Q

How are the alloantigens presented to host immune cells?

A
237
Q

Alloantigens can be delivered and presented to T-cells through 2 different pathways (figure-3):

Direct pathway: The transplanted organ carries number of passenger APCs in the form of interstitial dendritic cells. Direct pathway occurs when these donor’s APCs directly present their own antigens to recipient T-cells. As donor-origin APCs are depleted over time, the contribution of the direct pathway to the alloimmune response may decrease.

A

Alloantigens can be delivered and presented to T-cells through 2 different pathways (figure-3):

Indirect pathway: This occurs when host APCs capture and present donor’s antigens to recipient T-cells.

238
Q

imunossupressao

A
239
Q
A
240
Q

hypercalemia pos tx

A

Although the exact mechanism is unclear, calcineurin inhibitors (CNI), such as tacrolimus and cyclosporin, have been hypothesized to cause hyperkalemia through inhibitory effects on the Na/K ATPases in the distal tubules and luminal potassium channels as well as over activation of the distal sodium-chloride symporter (NCC).

Several non-immunosuppressive medications can also contribute to increases in potassium. These medications include angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), direct renin inhibitors, and potassium-sparing diuretics. Excretion of potassium declines due to inhibition of the RAAS pathway or a decrease in aldosterone levels leading to a reduction in the number of sodium channels and Na/K ATPase enzymes in the collecting tubules. Other medications, such as sulfamethoxazole-trimethoprim and pentamidine, are often used post-transplant and can contribute to hyperkalemia by competitively inhibiting sodium channels in the distal nephron.

241
Q

What is the likelihood of maternal complications if I do decide to get pregnant? apos tx

A

There is a 6 fold higher likelihood of preeclampsia in women who have a kidney transplant and a reported incidence of 15-25%. There is a also 5 fold higher risk of needing a cesarean section. However, there is no increased risk of maternal mortality.

242
Q

: Will I have a live healthy baby? gravidez e tx

A

: Likely Yes, having had a kidney transplant does not increase fetal mortality, especially if the timing is right and adequate precautions are taken (see below). However there is a 12 fold high likelihood of preterm and low birth weight babies; and a 3 fold higher likelihood of having small for gestational age babies.

243
Q

What are the risk factors associated with poor maternal and fetal outcomes?

A

The two most important risk factors are serum creatinine > 1.4 mg/dl, presence of hypertension during pregnancy and proteinuria > 500 mg/24h. It is advisable to become pregnant sooner than later – younger age at conception is associated with better outcome.

244
Q

Will pregnancy affect my allograft function?

A

Likely No, the kidney allograft is able to adapt normally to physiological changes of hyperfiltration in pregnancy. An uncomplicated pregnancy does not increase the risk of kidney loss. However it may affect graft function if you have risk factors like higher pre-pregnancy creatinine (or lower kidney function) or develop hypertension during pregnancy.

245
Q

What are the changes in immunosuppression that are made if I wish to become pregnant?

A

Mycophenolic acid (cellcept) and sirolimus are teratogenic, and must be stopped 6 weeks prior to conception. Cellcept has shown to be associated with limb and facial anomalies tacrolimus/cyclosporine (class C), azathioprine (class D) and low dose maintenance prednisone (< 20 mg/day) (class B) are safe to be used during pregnancy. Even though azathioprine is listed as class D, it is to safe to be used during pregnancy because the fetal liver lacks the enzyme inosinate pyrophosphorylase that converts it to active metabolite 6 mercaptopurine; and fetus is protected from its adverse effect.

246
Q

alvo dos imunossupressores

Agentes farmacológicos que induzem imunossupressão

A

Fase de indução da terapia imunossupressora •

Agentes biológicos

Tratamento de rejeição

Inibidores da calcineurina

Drogas anti-proliferativas

Inibidores da mTOR

Corticoides

247
Q

drogas imunossupressoras

A
248
Q

hiperuricemia e gota

A
  • Hyperuricemia is very common in KTRs. It increases the incidence of gout and other complications in KTRs, and it may be associated with loss of kidney function and CVD.
  • Suggest treating hyperuricemia in KTRs when there are complications, such as gout, tophi, or uric acid stones.
  • Suggest colchicine for treating acute gout, with appropriate dose reduction for reduced kidney function and concomitant CNI use.

Recommend avoiding allopurinol in patients receiving azathioprine.

• Suggest avoiding NSAIDs and COX-2 inhibitors whenever possible

249
Q

sindrome da intolerancia ao enxerto

A

Doença na qual os linfócitos T do doador reconhecem como estranhos os antígenos do receptor. Para que isto aconteça, algumas condições são necessárias: a)O implante deve conter células imunocomponentes; b)O receptor deve ter aloantígenos que diferem do doador, ou reconhecer autoantígenos de forma inadequada.

250
Q

BELATACEPT

A

The potential of targeting costimulatory molecules (e.g., CD40, CD80, CD86) has been one area of ongoing investigation. These costimulatory inhibitors target molecules that play central roles in T cell activation. One such agent, belatacept (Nulojix®, Bristol-Myers Squibb), was Figure 1: Incidence of first acute rejection among adult kidney transplant recipients, 2007-20112 3 approved by the US Food and Drug Administration (FDA) in 2011 for use in kidney transplantation in combination with other maintenance agents. Belatacept is a monoclonal fusion antibody that binds to CD80 and CD86. Studies have shown that belatacept is associated with higher risk of early acute rejection than a cyclosporine-based treatment combination, although longer term, comparable outcomes in patient and graft survival, as well as possible improvements in longer-term kidney function, and a more positive cardiometabolic profile have been noted.8, 10, 11, 12An increased incidence of post-transplant lymphoproliferative disease (PTLD), which is associated with Epstein-Barr virus (EBV), has been observed with the use of belatacept.11, 12 Therefore, the FDA approved belatacept only for use in EBV-seropositive kidney transplant recipients, and has issued a black box warning regarding PTLD. ASKP1240 (Astellas Pharma), another costimul

251
Q

imunossup

A
252
Q

VACINA E TX

A
253
Q

banff

A
254
Q

aumentam os niveis de ciclosporina

A

Eritromicina Azitromicina Claritromicina Cefalosporinas Cetoconazol Itraconazol Fluconazol Metronidazol Prednisona Cimetidina Verapamil Diltiazen Danazol Doxiciclina Nicardipina Tiazídicos Furosemida Contraceptivos orais

255
Q

interacao idiossincratica ciclosporina

A

Anfotericina B Tobramicina Aminioglicosídeos Altas doses de SMX + TMP Vancomicina Ranitidina Diclofenaco Indometacin

256
Q

diminuem os niveis de ciclosporina

A

rifampicina

isonizaida

nafcilina

Rifampicina Fenitoína Fenobarbital Carbamazepina Isoniazida Cotrimoxazol Sulfamida

257
Q

diminuem os niveis de tacrolimus

A

Rifampicina Fenitoína Fenobarbital Carbamazepina Barbitúricos Glicocorticoides

258
Q

posttransplantation lymphoproliferative disease (PTLD)

A

belatacept is an infusion that blocks the costimulatory signal between CD28 on T cells and antigen-presenting cells.

It typically supplants the use of CNIs and is used in conjunction with MMF or mTOR inhibitors and steroids.

There is an increased risk of PTLD with belatacept compared to cyclosporine, particularly in EBV negative patients. As a result, it is contraindicated in patients who are EBV negative or whose EBV status is unknown.

259
Q

gravidez pos tx

A

Women who wish to conceive are encouraged to discuss this with their physicians. The optimal scenario for conception is for the patient to (1) Substitute azathioprine for mycophenolate 3 months before conception (2) Be at least 1 year posttransplantation (3) Have a stable eGFR with SCr < 1.5 mg/dL with no recent rejection episodes (4) Have no significant proteinuria (5) Have well-controlled blood pressure without using an ACE-I or ARB

260
Q

diminuem os niveis de inib da calcineurina

A

Carbamazepine Phenytoin Phenobarbital INH Rifampin

261
Q

What is PRA?

A

PRA (PercentReactive Antibody) is the amount of HLA antibody present in a patient’s serum. As stated before, the patient could haveHLAantibody as a result of transfusions, prior transplants, and/or pregnancies. ThePRA is determined by testing the patient’s serum to a panel of 60 different types of HLA. If, for example, the patient’s serum reacts with 30 out of 60 HLA, then the patient’s PRA is 50% (1/2 of 60). The PRA is calculated for each monthly serum sample.

262
Q
A
263
Q

Declaration of Istanbul.

A

The Declaration of Istanbul published in 2008 emphasized that transplant tourism should be prohibited due to ethical considerations and to protect potential donors. There are exceptions; for example, if a donor and recipient are genetically related, they should be allowed to undergo the transplant in a country of their choice. Transplant tourism is legal in China and in Iran. China has a history of procuring organs from executed prisoners, which has been seen as a violation of the Declaration of Istanbul. In Iran, kidney sales are regulated.

264
Q

sistema abo

A

The donor and recipient generally must be ABO compatible. This can occur under one of the following circumstances: the donor and recipient are ABO identical, the donor has blood type O (universal donor), or the recipient is blood type AB (universal recipient). Given the distribution of blood group antigens in the United States, the waiting time on the deceased donor list is prolonged for patients with blood group O and B. A recipient with blood type B and a low anti-A Ag IgG titer can potentially receive a transplant from a donor with blood type A2B or A2 (

265
Q

Explain why organs from an individual with blood type A2 or A2B can be transplanted into a blood type B recipient?

A

A2 kidneys and A2B kidneys express little A antigen on their surface. If the potential candidate has a low anti-A Ag IgG titer (,4), they are able to receive an A2 or A2B kidney transplant. If the titer is high, then the candidate can only be eligible for a kidney from a donor with a B blood type. This allows for greater access to deceased donor kidneys for those with blood type B. This strategy is not limited to deceased donor kidney transplantation, but can also be used in living donor kidney transplantation.

266
Q

What is the potential use of Apolipoprotein L1 (APOL 1) gene variant testing in African American (AA) donors?

A

APOL1 is located on chromosome 22 and is associated with non-diabetic CKD in AAs. There are two kidney risk variants of APOL1 associated with CKD: 40% of AAs have one variant and 13% have two variants. Those with one variant have a 1.3-fold higher risk and those with two variants have a 7.3-fold higher risk of CKD. The role of APOL1 in evaluating kidney donors is not settled, but given the emerging data, it may be prudent to advise potential donors with APOL1 risk variants to avoid living donation.

267
Q

What is the recurrence of primary glomerulonephritis and the graft survival if a recurrence occurs at 5 years?

A

Focal segmental glomerulosclerosis recurrence rate of 35% with a 5-year graft survival of 73% •

Membranous nephropathy recurrence rate of 55% with a 5-year graft survival of 80%

• Membrano-proliferative glomerulonephritis recurrence rate of 40% with a 5-year graft survival of 54% •

IgA nephropathy recurrence rate of 51% with a 5-year graft survival of 81%

268
Q

What is a “sensitized” potential recipient?

A

A “sensitized” potential recipient is an individual who has detectable preformed HLA antibodies that pose considerable future risk to the allograft survival. Patient sensitization is classically reported as the percent panel reactivity antibody (PRA). PRA is defined as the percentage of donors expected to react with a patient’s serum based on known antibody. Highly “sensitized” patients often cross-match positive to multiple potential donors and require a zero antigen mismatch allograft to increase success. Consequently, these “sensitized” patients are less likely to be transplanted or will spend an extended time on the waitlist pending the availability of a suitable donor. The new allocation system, however, does give “points” for these individuals to increase their transplant rate.

269
Q

What are some methods to desensitize potential recipients who possess preformed HLA antibodies?

A

Intravenous immunoglobulin • Plasmapheresis • Rituximab • Splenectomy

270
Q

Induction

A

involves the use of powerful immunosuppressive agents to provide a high degree of immunosuppression immediately post-transplant. This prevents acute rejection and allows time for maintenance immunosuppression to be titrated to appropriate levels.

271
Q

recurrence uncommon, but can be severe immediately post-transplant

A

FSGS

272
Q

Maintenance immunosuppression’s objectives are to prevent rejection and safely preserve the function of the kidney allograft. These agents are used for the life of the transplant.

A

’s objectives are to prevent rejection and safely preserve the function of the kidney allograft. These agents are used for the life of the transplant.

273
Q

What are desensitization protocols?

A

Desensitization for the highly sensitized patients involves decreasing preformed antibody levels. This occurs prior to induction. There are several different methods that include various medications, including rituximab, bortezomib, intravenous immunoglobulin, plasmapheresis, and early initiation of maintenance immunosuppression weeks before transplantation. The outcomes have been equivocal. In addition, there is a significant financial cost as well as increased malignancy and infectious risk for the patient.

274
Q

What are the methods of induction therapy?

A

Induction strategies can be classified according to the mechanism of the agent used.

The two mechanisms that define these agents are lymphocyte-depleting and non-lymphocyte-depleting agents.

The lymphocyte-depleting agents used today are rabbit or equine anti-thymocyte globulin (thymoglobulin) and alemtuzumab (humanized anti-CD52 monoclonal antibody, Campath-1H, approved to treat chronic lymphocytic leukemia).

The non-lymphocyte-depleting agent used is basiliximab (interleukin-2 receptor antibody, anti-CD25).

Large pulse doses of steroids are also commonly used at the time of induction in addition to the lymphocyte- or non-lymphocyte-depleting agent. Overall, 85% of transplant programs use induction therapy, most commonly thymoglobulin followed by campath-1H and then basiliximab.

Basiliximab is used in those individuals at lower immunologic risk (e.g., Caucasian race, first transplant, older patient, low panel reactive antibody. The benefit is a better safety profile than lymphocyte-depleting agents—in other words, less risk of infection and cancer.

Those patients who are at higher risk for rejection should receive induction with a lymphocyte-depleting agent. The most common lymphocyte-depleting agent used today is thymoglobulin.

275
Q
  1. What are the main drugs used for maintenance therapy?
A
  1. Calcineurin inhibitors (CNI): tacrolimus, cyclosporine
  2. Anti-metabolites: azathioprine, mycophenolate mofetil (MMF), and mycophenolic acid (MPA)
  3. mTOR (mammalian target of rapamycin) inhibitors: rapamycin and everolimus
  4. Corticosteroids
  5. Selective co-stimulation blockade: belatacept

The most frequently used combination today is tacrolimus, anti-metabolite (MMF or MPA), and prednisone.

276
Q

Post-transplant lymphoproliferative disorder (PTLD)

A

PTLD is group of conditions that may happen after a transplant. It involves the immune system and causes lymphocytes to multiply out of control.

The seriousness varies from an overgrowth of the lymphocytes that is not harmful, to lymphoma.

PTLD is a complication of anti-rejection medicine; many cases are associated with infection with the Epstein-Barr virus (a member of the herpes virus family).

There are four (4) main types of PTLD:

Early lesions, which may often go away if your doctor can lower the dose of immunosuppressive drugs.

Polymorphic PTLD, has a mix of different types of cells.

Monomorphic PTLD, has 1 type of cell and is the most common type of PTLD.

Other types, which are rare, such as Hodgkin’s disease.

277
Q

aumento do risco de doença proliferativa pos transplante

A

The use of anti-lymphocyte globulin,

recipient EBV seronegativity=Recipient EBV seronegative status carried 5 times the risk for PTLD

recipient CMV seronegativity were all found to be risk factors for PTLD.

Donor EBV seropositivity did not achieve statistical significance as a risk factor for PTLD.

The incidence of PTLD was found to be lower in African Americans and patients who received IL-2RA.

Both ages less than 35 and over 65 were found to increase the risk for PTLD compared with the group aged 35-65.

278
Q

transplante HIV +

A

CD20 >200 E CARGA VIRAL NEGATIVA POR 6 MESES

DESFECHOS DO TX HIV +

papel da co infeccao do hcv na piora de tds os desfechos

mais risco de rejeicao

menor sobrevida do enxerto em 5-10 anos

maior taxa de infeccao

maior risco cv , metaboico e de dmo

sobrevida do paciente é igual

279
Q

vacinas

A

Acceptable vaccines Contra-indicated vaccines

Influenza vaccine (injected) MMR Vaccine

Inactivated poliomyelitis vaccine (salk)Poliomyelitis vaccine – live oral type – (sabin)

Pneumococcal vaccine Oral typhoid vaccine (vivotif)

Tetanus vaccine BCG

Meningococcal polysaccharide‘Shingles’ Varicella Zoster

Polysaccharide Typhoid vaccine (Typhum Vi)Smallpox vaccine

Cholera Yellow fever vaccine

Hep A/B Nasal influenza vaccine (live, mainly used in children)

280
Q

3 complications of higher risk deceased donors

A

More complex perioperative period

Higher risk of delayed graft function (need for dialysis post op)

Inferior long term allograft survival vs lower risk deceased donors

281
Q

Glomerulonefrite membranosa “de novo”:

A

Na maioria dos casos, a glomerulopatia membranosa (GNM) no transplante renal é uma doença “de novo”, ocorrendo em pacientes que tiveram outra patologia renal primária

. A recidiva é infreqüente. A incidência acumulada é de aproximadamente 1,5 a 2%.

Acredita-se que a GNM “de novo” possa estar relacionada a rejeição crônica, visto que a biópsia mostra alterações compatíveis com rejeição, em adição aos achados clássicos da GNM (espessamento da membrana basal e depósitos imunes no espaço subepitelial). O mecanismo permanece desconhecido. O início da proteinúria ocorre por volta de 18 a 21 meses pós-Tx.

282
Q

Why do live donor kidney transplants do better than deceased?

A

Healthier donors

Planned surgery

Very short cold ischemic time

Almost always have immediate graft function

Don’t have to wait

Shortest time to transplant (compared to deceased donor wait time)
Lowest perioperative risk

Better graft longevity

283
Q

treatment for FSGS that occurs post-transplant

A

plasmapheresis

284
Q

glomerulonefrite de novo pos tx

A

DLM= ocorre precocemente apos o tx, se apresenta como SINDROME NEFROTICA, esclerose mesangial leve e hipercelularidade sao as diferencas em relacao a dlm “normal”, tratamento com corticoide e prognostico bom

GESF= apresentacao com proteinuria mas SN rara, meses ou anos pos tx, sinais de rejeicao ou toxicidade por cni na bx, remover eventos associados, prognostico geralmente ruim pricipalmente na colapsante.recorrencia da gesf é precoce a de novo é tardia

gnMembranosa= proteinuria algumas vezes nefrotica, tardia pos tx, associada com complicacoes do tx, igG1 depoisitos ao inves de igg4,sem tto especifico, progressao lenta

Na maioria dos casos é uma doença “de novo”, ocorrendo em pacientes que tiveram outra patologia renal primária.. A recidiva é infreqüente. Acredita-se que a GNM “de novo” possa estar relacionada a rejeição crônica, visto que a biópsia mostra alterações compatíveis com rejeição, em adição aos achados clássicos da GNM (espessamento da membrana basal e depósitos imunes no espaço subepitelial).. O início da proteinúria ocorre por volta de 18 a 21 meses pós-Tx.

GNMP= proteinuria,hematuria, sn e sedimento nefritico. meses a anos pos tx, geralmente associada com hcv e outras doencas, tto= corticoide e drogas citotoxicas se tiver crescentes , progressao lenta, ruim se tiver crecentes

igA= hematuria, proteinuria, hematuria macro nao é freq, tto= corticoide e drogas citotoxicas se tiver crescentes , progressao lenta, ruim se tiver crecentes

285
Q

recorrencia

de novo

recorrencia de novo

A

recorrencia= volta a glomerulopatia q vc ja tinha

de novo= nova glomerulopatia

recorrencia de novo= vc teve um aglomerulopatia e perdeu a funcao renal, ai transplantou e teve uma gn de novo, perde esse rim e tranplanta e tem a iga novamente

286
Q

rejeicao do enxerto

A

2 immune mechanisms of graft rejection

T cell mediated (cellular rejection - acute rejection - can treat this well)
B cell mediated (Ab mediated rejection - long term - cannot treat this well)

287
Q

fatores que afetam o perfil do doador

A

Ten factors affecting KDPI:

  • Age (very important)
  • DCD (donation after circulatory death, important)
  • Weight • Height • Race (this is being debated to be removed)
  • HTN • DM
  • Death cause • Terminal serum creatinine • HCV • 100% means worst outcome, >85% risky, but still mostly better than dialysis. • Baseline serum creatinine (look at the trend not one point in time) if not immediately posttransplant
288
Q

doenças do rim nativo que determinam recorrencia

A
  • Oxalosis 80-100%
  • Diabetic Nephropathy 80-100% (by histology)
  • HUS/TTP 50-75%
  • IgA 40-60%
  • FSGS: 20-40% (can recur within minutes after transplant)
  • MPGN-I: 30-50%, II 80-100% (mind new classification

) • Membranous 10-30%

• GPA <20% • Fabry’s <5%, ↓a-galactosidase enzyme (Tx Fabrazyme) • SLE 5% • Significant post-transplant events including return to the OR, recent biopsies, infections, treatment for rejection etc • Immunosuppressive drugs and if any hold try to find out why (commonly due to low white count or infection

289
Q

Initial immunological assessment of a potential kidney transplant candidate

A
  • History of sensitizing events (eg previous transplant, blood transfusion, and/or pregnancy).
  • HLA typing of the donor and recipient,
  • Screening for alloantibody against HLA
290
Q

rejeicao aguda celuluar

A

TIPOI=inflamacao intersticial com TUBULITE

TIPO II= ENDOTELITE NA ARTERIA OU ARTERIOLA

291
Q

rejeicao cronica humoral (anticorpos)

A

glomerulopatia do transplante

membrana basal glomerular do capilar com varias camadas multilamelar

coloracao c4d no capilar peritubular linear

presença de dsa , hla ou nao hla no soro.

glomerulopatia do transplante cg>0 na ausencia de mat cronica

292
Q

rejeiçao aguda humoral ou mediada por anticorpos

Antibody-mediated or Humoral rejection (AMR)

A

GLOMERULITE, CAPILARITE PERITUBULAR, capilar peritubular com coloracao para c4d linear

presença do DSA no soro= hla ou nao hla

anticorpo anti doador

histologia:presença de pelo menos 1 GLOMERULITE G>0

PERITUBULAR CAPILARITE PTC>0

2-intimal ou transmural arterite v>0

3-MAT sem outra causa

4- injuria tubular aguda sem utra causa

evidencia histologica de interacao do anticorpo com ENDOTELIO VASCULAR, definido pela presenca de

c4d linear peritubular capilar pelo menos 10% na IF

inflamacao microvascular

injuria endotelial

PRESENÇA DE DSA; HLA ou nao HLA no soro

293
Q

contraindicacoes relativas

A

idade 18-21

has em negros

has em jovem

pre dm em jovem

imc 30-35

microalb ou ptnuria

alt da coagulacao

hist de trombose ou embolismo

nefrolitiase

hist de malignidade c mtx

dc cardiovasc significativa

294
Q

rejeicao

A

TUBULITE-

tubulo=celular

CAPILARITE /ARTERITE-

vaso = humoral

c4d e dsa

Nefrologia PT (112 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions