Nefropatia Por IgA

Question 1

Qual é a glomerulopatia primária mais comum?

Answer 1

Question 2

Quais são os tipos de apresentações clínicas da Nefropatia por IgA?

Answer 2

40-50% hematuria macro

30-40% hematuria assintomatica + proteinuria ate 2g

5% sindrome nefrotica

<5% obs27% desses >65a

ira: nefropatia crescentica por IGA ou NTA

eskd= mais velhos com iga nao diagnosticada

Question 3

Qual principal informação clínica para suspeitar de Nefropatia por IgA? Qual é o principal Dx diferencial?

Answer 3

Question 4

Tto da nefropatia por IgA:

Answer 4

tratamento de suporte para todos= controle da pa , dieta com pouco sal , proteina adequada

ieca ou bra

se mesmo assim proteinuria >1g = considerar a imunossupressao

Question 5

Quando fazer a imunossupressão na Nefropatia por IgA?

Answer 5

nefropatia por iga com crescentes= azatioprina , cicofosfamida,rituximabe

Patients with true rapidly progressive IgAN should be offered treatment with cyclophosphamide and glucocorticoids in accordance with the guidelines for antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis

RAS blockade should be instituted irrespective of hypertension if the patient has proteinuria >0.5 g/d

Busca-se reduzir a pressão arterial para 125/75 mmHg e proteinúria para níveis £ 0,5g/dia

If proteinuria stays above 0.75–1 g/d despite at least 90 days of optimized supportive care, the patient has a high risk of progressive loss of kidney function and may be considered for a 6-month course of glucocorticoid therapy

Because the clinical benefit of glucocorticoids in IgAN is not established, they should be given with extreme caution or avoided entirely in patients with:•an eGFR <30 ml/min per 1.73 m2,diabetes,•obesity (defined as body mass index >30 kg/m2),latent infections (e.g., viral hepatitis, tuberculosis),secondary disease (e.g., liver cirrhosis),active peptic ulceration,•uncontrolled psychiatric disease, or severe osteoporosis.

Management of the patient with IgAN who remains at high risk for progression after maximal supportive care is illustrated in Figure 2. Proteinuria reduction to under 1 g/d is a surrogate marker of improved kidney outcome in IgAN, and hence a reasonable treatment target.

Question 6

Qual classe de medicamento que recentemente mostrou proteção renal na nefropatia por IgA?

Answer 6

Question 7

fatore de risco para progressao

Answer 7

tfg baixa, proteinuria e has

glomeruloesclerose segmentar, fibrose intersticial, e proliferacao endocapilar =fatores de risco para a progressao (histologicos)

quase 50% dos pacs apos 20anos de dc irao evoluir para eskd

Question 8

fisiopatologia IgA

Answer 8

GLICOSILACAO ANORMAL DA IGA

clearance hepatico de igA diminuido devido a essas alteracoes

4 hits da igA

1) produçao de igA anomala= IgA1 anomala =deficiencia de galactose na regiao de dobradiça- galactose-deficient-igA
2) formacao de c=anticorpos circulantes contra a iga anomala=formacao de igG contra
3) formacao de complexos antigenos-anticorpos=interacao entre a igA anomala e os anticorpos formados contra essa imunoglobulina formam complexos imunes do tipo antigeno (iga anomala)+anticorpo (igG). formacao desses complexos dificulta o clearance sistemico (normalmente nos macrofagos hepaticos)

eventualmente esses complexo imune inclui ptns do complemento C3 e podem formar polimeros circulantes

4)formacao de polimeros mesangiais que incluem a IgA=complexo é filtrado pelo rim, escapa pelos capilares pelas fenestras do endotelio e no mesangio ativacao da inflmacao mesangial.leva a producao de citocinas e quimiocina inflamatorias que irao afetar a dinamica glomerular determinando formas de acometimento glomerular e fibrose tecidual.

a presença do composto mesangial estimula a proliferacao do mesangio (aumento da matriz) e expansao das cels mesangiais

i

Question 9

Algumas situações merecem comentários à parte, quadros de síndrome nefrótica com lesões histológicas mínimas e depósitos imunes de IgA no mesângio, respondem ao corticóide com 80% de remissão semelhante a nefropatia de lesões mínimas idiopática

Question 10

diagnostico so c bx

Determine the MEST-C score (mesangial [M] and endocapillary [E] hypercellularity, segmental sclerosis [S], interstitial fibrosis/tubular atrophy [T], and crescents [C]) according to the revised Oxford Classification.

There are no validated diagnostic serum or urine biomarkers for IgAN.
Assess all patients with IgAN for secondary causes.

Answer 10

Prognosis
Practice Point 2.2.1: Considerations for the prognostication of primary IgAN:
Clinical and histologic data at the time of biopsy can be used to risk stratify patients.
The International IgAN Prediction Tool is a valuable resource to quantify risk of progression and inform shared
decision-making with patients.
B Calculate by QxMD
The International IgAN Prediction Tool incorporates clinical information at the time of biopsy and cannot be used to
determine the likely impact of any particular treatment regimen.
There are no validated prognostic serum or urine biomarkers for IgAN other than eGFR and proteinuria.

Question 11

imunocomplexos patogenicos

Answer 11

resultados

injuria dos podocitos e cels do tubulo proximal

piora da funcao com progressao para drc

que pode levar a eskd

Question 12

potential new diagnoostic e markers

Answer 12

serum level galactase deficient iga

Question 13

A Nefropatia da IgA

Answer 13

é uma glomerulopatia primária que cursa com recorrência de hematúria microscópica ou macroscópica, associada a episódios de infecção de vias aéreas superiores.

Maioria dos casos apresenta curso benigno, sendo infreqüente a evolução com piora de função renal, associação com hipertensão ou presença de proteinúria em níveis nefróticos

. Não tem marcadores laboratoriais típicos, apresentando níveis normais de complemento. Predomina no sexo masculino, com pico de incidência na segunda e terceira décadas de vida.

Casos com piora de função renal e proteinúria em níveis nefróticos ocorrem com maior freqüência em pacientes mais velhos à apresentação, presumindo-se que sejam indíviduos em que o diagnóstico não foi feito de forma precoce devido curso com hematúria microscópica.

Question 14

glomerulonefrite MESANGIOPROLIFERATIVA

IgA

Answer 14

unlike Henoch-Schonlein nephritis, IgA
nephropathy (IgAN) is limited to the kidneys.

• Common cause of glomerulonephritis worldwide.
• Mesangioproliferative lesions with predominant IgA deposition by immunofluorescence.

Question 15

IgA -CLÍNICA

Answer 15

Clinical Features
• Gross hematuria is often the first presenting symptom 24-48 hours following a pharyngeal or gastrointestinal infection, vaccination, or strenuous exercise

.
• Asymptomatic cases present with microscopic hematuria during a routine physical.

• Varied array of presentations – ranging form intermittent gross
hematuria to persistent microhematuria.

• Constitutional symptoms (fever, muscle aches, malaise, fatigue, and flank/abdominal pain) often manifest.
• Others may present with associated diseases such as alcoholic cirrhosis,celiac disease, dermatitis herpetiformis, ankylosing spondylitis, and human immunodeficiency virus infection.

Question 16

PATOLOGIA

Answer 16

Light Microscopy – findings may range from normal findings to focal or diffuse mesangioproliferative glomerulonephritis. There may be focal ordiffused mesangial hypercellularity and endothelial proliferation with leukocyte infiltration.

As the disease progresses, there will be apparent glomerular sclerosis with tubular atrophy, interstitial fibrosis, and
interstitial infiltration by mononuclear leukocytes

• Immunofluorescence – diffuse glomerular IgA immune deposits, which are deposited in a diffuse granular pattern located primarily within the mesangium. Some IgG or IgM staining may be observed but is less prominent. Unlike other glomerular immune complex diseases, the lambda light chains will be more intensely stained than the kappa light chains. Among patients with severe disease, substantial capillary wall
staining will occur but subepithelial deposits are not commonly observed.
C3 deposits may also be observed in the same pattern as the IgA
deposits

• Electron Microscopy – Electron-dense deposits correspond to the immune deposits. There is mesangial matrix expansion and hypercellularity corresponding to the light microscopic findings. Epithelial foot process effacement is present in those patients with substantial proteinuria.

Question 17

DEPÓSITOS MESANGIAIS

Answer 17

dépositos granulares difusos de IgA

90% C3

40% IGM

40%IGG

PODE TER KAPPA E LAMBDA

Question 18

tto

Answer 18

MEST-C classificacao de Oxford

M=hipercelularidade mesangial = >4 cels em qualquer area do mesangio no glomerulo

M0 <50% do glomerulo com hipercelularidade mesangial

M1 = >50% do glomérulo

E=hipercelularidade endocapilar=aumento do numero de celulas dentro do lumem capilar

E0= sem hipercelularidade capilar

E1= qualquer glomerulo mostrando hipercelularidade capilar

S=segmentar glomeruloesclerose=GESF=adesao ou esclerose de parte do tufo glomerular

S0=SEM

S1=presente em qualquer glomerulo

T=atrofia tubular ou fibrose intersticial

T0 =até 25% T1=26-50% T2>50%

C=crescente celulares ou fibroticas

C0=sem

C1= ate 25%

C2=>35%

Question 19

considerar causas secundarias

Answer 19

• vasculite por Iga
• igA secundaria a hiv hepatites

cirrose

dç inflamatoria intestinal

dc autoimune

GN relacionada a infeccao igA dominante

Question 20

estratificacao de risco usando igA predicition tool

Answer 20

determina o risco de queda da tfg em 50% ou evolucao para eskd em 6-7 anos

Question 21

TRATAMENTO

Patientshould receive a 6 month course of corticosteroid with persistent proteinuria>1g/24hr, despite 3-6 month of optimized supportive care

Answer 21

PROTEINURIA >1G mesmo depois de 3 meses de medidas de suporte otimizadas=

inicio de bra/ieca =dose max tolerada

mudancas no estilo de vida

manejo da pa

ALVO PS <120

se tfg> 30 avaliar o risco beneficio do uso de corticoides

riscos nao fazer: obesidade, indeccao latente, diabetes, cirrose, ulcera peptica ativa, dc psiquiatrica , osteoporose,idade avancada, sindrome metabolica

predinisona >0,5mg/kg/dia fazer profilaxia de oneumonia por pneumocisto, protecao gastrica e ossea

tonsilectomia nao deve ser feito de rotina em caucasianos

Question 22

estudos

Answer 22

obs: populacoes especificas

japoneses= considerar tonsilectomia

chineses= considerar micofenalota como poupador de corticoide

Question 23

dapa ckd inclui pacs com iga

Answer 23

Question 24

variantes da apresentacao da igA

Answer 24

IgA Rapidamente progressiva=piora de >50% da TFG em menos de 3 meses onde outras causas e causas reversiveis foram excluidas

biopsia com hipercelularidade mesangial e crescente em mais de 50% do glomerulo

tratemento com CICLOFOSFAMIDA E CORTICOIDE

igual vasculite assoc a ANCA

obs - se tiver crescente na bx mas n tiver progressao da dr nao é gnrp

Question 25

variantes da apresentacao da iga

Answer 25

ira por hematuria macica

pode ser biopsiado 2 semanas apos a hematuria

igA com SN=raramente se apresenta assim , me pode ser consistente com dlm e deve ser tratado como tal

igA com proteinuria nefrotica mas sem SN=mais associada a GESF

Question 26

VASCULITE POR IGA

Henoch-Schonlein Purpura (Anaphylactoid purpura or Rheumatoid
purpura)

Answer 26

Classic triad of (1) palpable purpura, (2) arthralgias, (3) gastrointestinal manifestations, and associated glomerulonephritis.

• Renal involvement of HSP is similar to that IgA nephropathy.
• IgA-containing immune complexes deposit in the skin, kidney, and other organs with associated inflammatory reaction of the vessels.

crianças entre 4-7anos, mais em meninos

Question 27

vasculite por igA

Answer 27

About 30-50% of the cases may have preceding upper respiratory infection before presentation.

o Reports of allergies, insect bites, foods, other vial illnesses,
trauma, and drugs may be associated but most of the cases do
not have any links to specific exposure.

• Constitutional symptoms are common, fever and weight loss is also seen.
• Bleeding and hemorrhage seen in some patients.
• Only about half of the patients may present with the classic triad listed above.
• Virtually all patients will have the skin lesions.

o Red-violet urticarial macular and papular lesions that do not
blanch with pressure will commonly appear symmetrically on the lower extremities and buttocks but may be present anywhere
(e.g. elbows).

• Edema may be present even without proteinuria.
• Arthralgia occurs mainly joints of the extremities, commonly knee and ankles.
o May be migratory in nature and may have associated swelling of the joint.

• Gastrointestinal manifestations – vomiting, diarrhea, colicky pain,melena, and hematochezia. Laparotomy will show punctate hemorrhages in the bowel wall.

o Symptoms may lead to rare complications such as
intussusception and necrosis, which eventually causes
perforation.

• Renal disease is not always present in HSP and may appear weeks after initial presentation. Patients with renal involvement typically have microscopic hematuria, active urinary sediment, and proteinuria.

o Approximately 50% of the cases will have nephrotic syndrome
that appears within days to weeks of the initial symptoms.
Severity of the disease does not correlate with the severity of
the renal involvement.

Question 28

patogenese

Answer 28

Like IgA nephropathy, the pathogenesis of this disease is unknown.
• Appears to be a systemic immune complex disease with IgA-containing circulating immune complexes (CICs), which are associated with a small- vessel vasculitis and capillary damage.

• IgA-containing complexes and antibodies; complement activation; platelet activation and coagulation; and vasoactive prostanoids, cytokines, and growth factors may all play a role.

Question 29

patologia vasculite por iga

Answer 29

Light microscopy – Findings of HSP are similar to those of IgA
nephropathy.

• Mesangioproliferative glomerulonephritis +/- crescents.

o There is mesangial cellularity with focal or diffused matrix
expansion.
o Immunofluorescence – IgA deposits are seen with IgG, IgM, and C3 located in the mesangial and paramesangial regions. The IgA deposits are of IgA1 that may contain polymeric J chains.

o Electron microscopy –Characteristic immune-type electron-
dense deposits are found in the mesangial region,accompanying an increased in matrix and cellular proliferation.
Patients with severe crescent formation, capillary walls may be disrupted and damaged causing lysis of the basement
membranes seen on EM.

Question 30

vasculite por igA

diagnostico

Answer 30

geralmente o diagnostico é clinico mas pode biopsiar em casos de

• proteinuria >1g
• gnrp
• falencia renal

em adultos tem que investigar causas secundaria

plasmaferese pode ter lugar+ corticoide

Question 31

aconselhamente pre concepcional

Answer 31

otimizar antihas

parar bra e ieca

avaliar imunossupressao naquelas q tem risco d eprogredir

antes de tentar engravidar pra diminuir a proteinuria

Question 32

iga

Answer 32

IgAN- Proteinuria ismore than 1 g/d

long-tern ACE-1 or

ARB•

Blood pressuretarget- 125/75

IgAN -Proteinuria is morethan 1 g/d despite 3-6months ARB/ACE and BP 125/75and GFR more than 50ml/min

•

6-months course ofcorticosteroid therapy ontop of ACE/ARB

•

Crescentic IgAN

•

Steroids andcyclophosphamide

analogous to the

treatment of ANCA

vasculitis