A1262590213MitGc

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Frecuencias de Glomerulopatías Primarias en
cuatro períodos de ingreso al Registro
CHI-CUADRADO P lt 0.001
Figura 2
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Registro Uruguayo de Glomerulopatías HFS
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PRESENTACIÓN CLÍNICA
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Proteinuria al Ingreso
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Creatininemia al ingreso
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Tasa evolución. IRE (100 ptes/ años) RR (edad, sexo, período)
Vasculitis 33.3 9.1
Amiloidosis 25.5 5.9
MPGN 18.7 5.1
HFS 9.9 3.9
Nef. Lúpica 5.8 3.6
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FSGS ESRD rates
 
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Table 1. Etiologic Classification of FSGS

• Primary (idiopathic) FSGS
• Secondary FSGS
• 1. Familial/genetic
• A. Mutations in -actinin 4
• B. Mutations in podocin
• C. Mutations in WT-1
• D. Mutations in integrin
• 2.Virus-associated
• A. HIV-1 (HIV-associated nephropathy)
• B. Parvovirus B19
• 3. Drug-induced
• A. Heroin (heroin nephropathy)
• B. Interferon-
• C. Lithium
• D. Pamidronate

• 4. Mediated by adaptive structural-functional
  responses
• A. Reduced renal mass
• Oligomeganephronia
• Unilateral renal agenesis
• Renal dysplasia
• Reflux nephropathy
• Sequela to cortical necrosis
• Surgical renal ablation
• Chronic allograft nephropathy
• Any advanced renal disease with reduction in
  functioning nephrons
• B. Initially normal renal mass
• Hypertension
• Atheroemboli or other acute vaso-occlusive
  processes
• Obesity
• Cyanotic congenital heart disease
• Sickle cell anemia

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Tabla 2. Glosario de términos

• Adhesión Continuidad de la matriz de colágeno
  entre el ovillo glomerular y la cápsula de Bowman
• Colapso Colapso implosivo de la pared capilar
  con plegamiento de la membrana basal glomerular
  causando obliteración de la luz capilar sin
  aumento de la matriz o células intracapilares
• Confluencia de los podocitos con las células
  parietales o epiteliales tubulares en la luz
  tubular o cuello contacto celular directo de los
  podocitos con las células epiteliales parietales
  o las células tubulares epiteliales en la luz
  tubular o el cuello

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• Hipercelularidad endocapilar Oclusión de los
  capilares glomerulares por un aumento absoluto en
  el número de las células intraluminales, que
  pueden incluir células espumosas, células
  endoteliales, macrófagos, y otros leucocitos, a
  veces asociada con hialinosis, kariorrexis, y
  raramente fibrina, frecuentemente produciendo una
  lesión expansiva
• Focal Que compromete algunos pero no todos los
  glomérulos
• Global Que afecta todo el ovillo glomerular
• Glomerulomegalia Ovillo (Tuft) glomerular de
  mayor tamaño que los controles de la misma edad (
  con la medida de área glomerular gt 1.5 x normal)

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• Hialino acumulación de material proteinaceo
  eosinofílico homogéneo vidrioso (smooth and
  glassy)
• Hipercelularidad Mesangial gtde 3 células
  mesangiales rodeadas por matiz mesangial en un
  segmento glomerular intacto, observado en cortes
  de 3 µm de espesor
• Perhiliar Compromiso segmentario vecino al hilio
  glomerular
• Hiperplasia podocitaria Aumento del número de
  los podocitos, usualmente con acumulación y
  formación de multicapas a diferencia de las
  semilunas verdaderas, estas lesiones típicamente
  carecen de eje celular, matriz peri-celular,
  fibrina extracapilar o continuidad con las
  células epiteliales parietales

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• Hipertrofia podocitaria aumento del tamaño de
  los podocitos con o sin gotas de reabsorción
  proteica intracitoplasmática, vacuolas,
  agrandamiento y vesiculización nuclear y
  nucléolos prominentes
• Esclerosis Aumento de la matriz glomerular
  extracelular con obliteración de la luz capilar
  glomerular
• Segmentaria compromiso del ovillo glomerular
• lt 100 con algunos capilares glomerulares
  evidentes
• Dominio TIP porción externa del ovillo
  glomerular (25) cercana al origen del túbulo
  proximal (el polo tubular debe ser identificado)
• Ovillo (Tuft) El flóculo glomerular, no incluye
  la cápsula ni el espacio de Bowman

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Propuesta

• Clasificación morfológica
• Para profundizar en etiología debe realizarse
  inmunofluorescencia y M.Electrónica
• Inicialmente debe descartarse HFS secundaria a
  otras glomerulopatías
• Base para evaluar posibles evoluciones diferentes

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CLASIFICACIÓN

• NOS (clásica)
• Perhiliar
• Celular
• Lesión Tip
• Colapsante

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FSGS (NOS)(Not Otherwise Specified)- clásica-

• Criterios de Inclusión
• Por lo menos 1 glomérulo con aumento segmentario
  de la matriz obliterando la luz capilar
• Puede existir colapso segmentario de la pared
  capilar glomerular sin hiperplasia podocitaria
  por encima
• Criterios de exclusión
• Variante Perhiliar
• Variante Celular
• Variante Tip
• Variante Colapsante

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(A) FSGS (NOS). A low-power view shows segmental
lesions of sclerosis in all 4 glomeruli pictured.
Lesions of sclerosis are characterized by
increased matrix, causing obliteration of the
capillary lumina. Distribution of lesions within
the tuft is variable, affecting both peripheral
and perihilar segments. In some glomeruli, the
location of the sclerosis cannot be ascertained
because of the plane of section. (JMS original
magnification 100.) (B) FSGS (NOS). High-power
view of a glomerulus shows a discrete segmental
lesion of sclerosis with wrinkling and collapse
of glomerular basement membranes (stained blue)
and hyaline deposits (stained red).Overlying the
wrinkled capillaries, there is detachment of
podocytes, which form a cap, with intervening
deposition of looser neomembrane that is weakly
trichrome-blue positive. Although the capped
podocytes appear hypertrophied,there is no
podocyte hyperplasia. (Masson trichrome original
magnification400.)
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(C) FSGS (NOS). There is segmental obliteration
of the glomerular tuft by increased matrix and
hyaline material. Sclerosed segments form
adhesions to Bowmans capsule. There is no
obvious podocyte hypertrophy or hyperplasia. The
location of the sclerotic lesion within the
glomerular tuft cannot be determined because
neither the tubular nor the vascular pole are
represented in the plane of section. (PAS
original magnification250.)
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FSGS Perhiliar

• Criterios de inclusión
• Por lo menos 1 glomérulo con hialinosis perhiliar
  con o sin esclerosis
• gt50 de los glomérulos con lesiones segmentarias
  deben tener esclerosis o hialinosis perhiliar
• Criterios de exclusión
• Variante Celular
• Variante Tip
• Variante Colapsante

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(D) FSGS perihilar variant. On low-power
examination, 1 of the 3 glomeruli pictured
contains a discrete lesion of segmental sclerosis
affecting the vascular pole region. The lesion
shows both increased matrix (sclerosis) and
hyalinosis. There is adhesion of the sclerotic
segment to Bowmans capsule in the vascular pole
region. Perihilar lesions were identified in more
than 50 of glomeruli with segmental sclerosis.
Both the glomerulus with segmental sclerosis and
the 2 nonsclerotic glomeruli are hypertrophied in
this patient with morbid obesity. (PAS original
magnification 100.) (E) FSGS perihilar variant.
High-power view of the perihilar lesion in (D)
shows both the increased matrix (sclerosis) and
glassy hyalinosis deposited in the vascular pole
segment of the tuft,identified by the incoming
arteriole and macula densa. There is no obvious
podocyte hypertrophy or hyperplasia.
(PASoriginal magnification 250.)
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(F) FSGS perihilar variant. A very early lesion
illustrates the mild increase in matrix and
hyaline surrounding the glomerular hilus. There
also is hyalinosis of the adjacent preglomerular
arteriole. The glomerulus is hypertrophied in
this patient with a solitary functioning kidney.
(PAS original magnification 250.)
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FSGS Celular

• Criterios de Inclusión
• Por lo menos 1 glomérulo con hipercelularidad
  segmentaria endocapilar ocluyendo la luz con o
  sin células espumosas o kariorrexis,
  comprometiendo por lo menos 25 del ovillo
• Habitualmente existe hipertrofia e hiperplasia
  podocitaria pero no es un hecho requerido para el
  diagnóstico
• Criterios de exclusión
• Variante Tip
• Variante Colapsante

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FSGS cellular variant. (A) The defining
glomerulus in this patient with primary FSGS
shows segmental endocapillary hypercellularity.
Involved segments are engorged with endocapillary
cells, including some infiltrating mononuclear
leukocytes. (HE original magnification 250.)
(B) In the cellular variant, silver stain shows
expansion of the involved segments by
endocapillary cells (not matrix), including foam
cells and some karyorrhectic leukocytes. No
glomerular capillary wall collapse is seen. There
is hypertrophy and hyperplasia of the overlying
podocytes. (JMS original magnification 400.)
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(C) This example of the cellular lesion shows
numerous endocapillary leukocytes, mimicking a
segmental endocapillary proliferative
glomerulonephritis. There is hypertrophy and
hyperplasia of overlying podocytes. Adjacent
glomerular segments have mild mesangial
hypercellularity. (HE original magnification
400.) (D) High-power view of a cellular lesion
shows karyorrhectic nuclear debris, admixed with
foam cells and hyaline material. Overlying
podocytes are hyperplastic. (HE original
magnification 600.)
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FSGS Tip

• Criterios de inclusión
• Por lo menos 1 lesión segmentaria que compromete
  el dominio tubular (Tip) (25 externo del tuft
  cercano al origen del túbulo proximal)
• El polo vascular debe estar identificado en la
  lesión
• La lesión debe tener o una adhesión o confluencia
  de podocitos con células parietales o tubulares
  en la luz o el cuello tubular
• La lesión puede ser celular (lt50 ovillo)
• o esclerosante (lt25 ovillo)
• Criterios de exclusión
• Variante colapsante
• Cualquier lesión perhiliar

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FSGS tip variant. (A) Low-power view shows a
segmental lesion involving the tip domain at the
origin of the tubular pole. The vascular pole is
not visible in this plane of section. (PAS
original magnification 250.) (B) High-power view
of the lesion in A shows the involved segment to
contain endocapillary foam cells and form an
adhesion to Bowmans capsule at the mouth of the
proximal tubule. There is capping of the
overlying podocytes, which become confluent with
the adjacent tubular epithelium. (PAS original
magnification 600.)
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(C) Low-power view shows the portion of the
glomerular tuft involving the tip domain to be
expanded by a segmental lesion with cellular
features located at the tubular pole. (PAS
original magnification250.) (D) High-power view
of the tip lesion in C shows endocapillary foam
cells admixed with a few leukocytes. There is a
small adhesion of the tuft to Bowmans capsule at
the tubular pole. Overlying podocytes appear
confluent with the adjacent tubular epithelial
cells. (PAS original magnification 600.)
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(E) Opposite the vascular pole, the origin of the
proximal tubule is visible.In this area, there is
an early tip lesion with inframembranous
hyalinosis, a few endocapillary foam cells, and
confluence of swollen podocytes with the tubular
epithelium. (PAS original magnification
250.) (F) In this glomerulus, the tip lesion
appears to herniate into the tubular lumen and
forms a capsular adhesion. (PAS original
magnification 250.)
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FSGF Colapsante

• Criterios de inclusión
• Por lo menos 1 glomérulo con colapso segmentario
  o global con hipertrofia e hiperplasia
  podocitaria por encima
• Criterios de exclusión
• No

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FSGS collapsing variant. (A) A low-power view
shows 4 glomeruli, all of which have global
collapse of the tuft and podocyte hypertrophy and
hyperplasia. There are associated tubular
degenerative changes. (JMS original
magnification 100.) (B) On high-power view, the
lesion of collapsing sclerosis shows global
occlusion of capillary lumina by implosive
collapse of glomerular basement membranes. There
is no appreciable increase in intracapillary
cells or matrix. Overlying podocytes form a
cellular corona over the collapsed tuft. Some of
the enlarged podocytes appear binucleated and
have lost their cohesion to the tuft. (JMS
original magnification 400.)
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(C) An example of global collapse of the
glomerular tuft with marked overlying podocyte
hyperplasia, forming a pseudocrescent that fills
the urinary space. An apoptotic podocyte has
detached from the tuft and is passing into the
tubular pole. (JMSoriginal magnification 400.)
(D) Hyperplastic podocytes contain numerous
intracytoplasmic protein resorption droplets,
which appear red with trichrome stain. The
collapsed tuft, shown in blue, has no patent
capillary lumina. (Masson trichrome original
magnification 400.)
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(E) Hyperplastic podocytes form several layers of
cells over the collapsed tuft. Some of the
swollen podocytes contain intracytoplasmic
vacuoles. Podocyte nuclei have a vesicular
chromatin pattern with prominent nucleoli. (JMS
original magnification 400.) (F) A segmental
lesion of collapsing sclerosis spares more than
half the tuft. Collapsed capillaries have
prominent overlying podocyte hypertrophy and
hyperplasia, with abundant trichrome-red
intracytoplasmic protein resorption droplets.
(Masson trichrome original magnification 400.)
(G) By electron microscopy, the collapsed loop
has folded glomerular basement membranes, with
complete effacement of foot processes. Overlying
podocytes are detached from the glomerular
basement membrane with intervening layering of
neomembrane material. (Original magnification
2,500.)