IN THE NAME OF GOD

RENAL PATHOLOGY

DR. Z. VAKILI

Glomerular Syndromes and Disorders

Nephrotic Syndrome
a) massive proteinuria (> 3.5 g/day)
b) hypoalbuminemia
c) generalized edema
d) hyperlipidemia and lipiduria

Nephrotic Syndrome
Initial event is derangement of GBM
increasing permeability and progressive
loss of plasma proteins hypoalbuminemia decrease in
plasma volume plasma colloid osmotic pressure
aldosterone ANP, GFR edema
water and solute retention by
;kidney exacerbation of edema (anasarca
(; massive amounts of edematous fluid
hypoalbuminemia lipoprotein production
by the liver

Nephrotic Syndrome
In children < 15 yrs, nephrotic syndrome
almost always caused by primary renal
disease (~ 98 %)
In adults nephrotic syndrome may often
be associated with secondary renal
disease

Minimal change disease

(Lipoidnephrosis; Epithelial cell disease)
a) major cause of nephrotic syndrome in
children < 15 yrs;
b) peak 2-6 yrs
i) also in adults with nephrotic
syndrome
(~ 20 %)
c) effacement of foot processes
d) glomeruli show only minimal changes

Minimal change disease

(Lipoidnephrosis; Epithelial cell disease)
e) most patients are boys who usually
present prior to 6 yrs of age
i) selective proteinuria (albumin)
ii) history of recent Ag exposure ??

f) idiopathic (sometimes follows respiratory

infection or routine immunizations)

Minimal change disease

(Lipoidnephrosis; Epithelial cell
g) T cell involvement
suggested
disease)

i) patients present w/ similar S & S

ii) epithelial cell diseases have altered T ell

function
h) loss of lipoproteins through the glomeruli
accumulates lipids in proximal tubule cells
foamy cytoplasm ,together with lipids in the urine
LIPOID NEPHROSIS
i) remission w/in 8 weeks with use of corticosteroid use
(very dramatic response is one hallmark of this disease)

Minimal change disease

(Lipoidnephrosis; Epithelial cell disease)
j) relapses do not tend to progress to chronic renal
failure
k) development of azotemia should suggest
incorrect diagnosis of minimal change disease
l) in absence of complications, outcome of
patients with epithelial cell disease is
same as general population

Minimal Change Dis

:Minimal Change Disease

Loss of Foot processes

Membranous Glomerulopathy
(epithelial cell and BM disease)
a)most common cause of nephrotic
syndrome in adults (C5-C9 cytotoxic)
b)diffuse thickening of glomerular capillary wall !!
c) most cases are idiopathic
i) most believed to be autoimmune
d) most glomeruls are normocellular or only
mildly hypercellular

Membranous Glomerulopathy
(epithelial cell and BM disease)
e) believed to be caused by
i) deposition of immune complexes
w/in capillary wall
- IgG and C3
ii) formation of in situ immune
complexes
iii) refer to Heymans nephritis
iv) classified as non inflammatory
since
there is NO cellular

Membranous Glomerulopathy
(epithelial cell and BM disease)
f) In adults, a frequent association is with
carcinoma !! (i.e., melanocarcinoma, lung and
colon Cancer)
g) associated with systemic infections and disease
i) HBV
ii) SLE
h) associated with certain drug treatments
i) gold, penicillamine, NSAID

Membranous Glomerulopathy
(epithelial cell and BM disease)
Clinical

a) variable
i) spontaneous remission
ii) renal failure w/in 10-15 yrs
b)persistent proteinuria w/ normal
function
c) better response to corticosteroids
in children vs. adults

Membranous Glomerulopathy
(epithelial cell and BM disease)
d) Progression of disease
i) stage I: small granular subepithelial
deposits
i) stage II: spikes of BM protrude
between deposits of electron
dense material (e.g., IgG,
C3)
iii) stage III: deposits of electron dense
material are incorporated into
GBM
iv) stage iv: GBM very distorted and

:Membranous GN

:Normal Kidney

Normal Glomerulus (PAS)

Focal segmental glomerulosclerosis

(epithelial cell and BM disease)
a) some glomeruli exhibit segmental
areas
of sclerosis whereas others are
normal
b) nephrotic
i) most commonsyndrome
cause of nephrotic syndrome in
USA

Focal segmental
glomerulosclerosis
(epithelial
cell
and BM disease)
c) occurs
in the following
setting:

i) associated with other conditions

- HIV
)
- heroin addiction
- sickle cell disease
- morbid obesity
ii) secondary event
- IgA nephropathy
iii) adaptive process to loss of kidney
- renal ablation
- advanced stages of other renal diseases
(e.g.hypertension)
iv) primary disease (e.g., idiopathic focal segmenta
glomerulosclerosis)

Focal segmental glomerulosclerosis

(epithelial cell and BM disease)
d) differs from minimal change disease
i) higher incidence of hematuria,
reduced GFR, and hypertension
ii) poor response to corticosteroids
iii) proteinuria is non selective
iv) progression to chronic
glomerulosclerosis
v) IgM and C3 trapping on sclerotic
segments

Focal segmental glomerulosclerosis

(epithelial cell and BM disease)

vi) whether this is a specific disease or

is an evolution of minimal change disease is
unresolved !!
- degeneration of visceralepithelial cells
hallmark
of FSGN
- similar cell damage as seen in minimal
change disease

Focal segmental glomerulosclerosis

(epithelial cell and BM disease)

vii) genetic basis

-NPHS1 gene
-encodes nephrin
- several mutations of this gene give rise to
congenital nephrotic syndrome of the Finnish type (CNF)
-NPHS2 gene
- encodes to podocin
- mutations give rise to steroid resistant nephrotic
syndrome in children

Focal segmental
glomeruloscleros

Membranoproliferative GN
a) characterized by GBM thickening (i.e., membrano) +
mesangial cell proliferation (proliferative )
b) two major groups: Types I and II (+ III)
i) Type I: majority of cases are idiopathic.
Associations with
- HBV
- HCV
- bacterial endocarditis
- strep infections
- granular deposition of Ig (IgG, IgM)
and complement (C3) and C1q and C4

Membranoproliferative GN

ii) type II (and III)

- circulating C3 Ab (C3 nephritic factor)

C3 (hypocomplementemia)
- characteristic ribbon-like zone of
cellularity on thickened GBM
(dense deposit disease)

Membranoproliferative GN

c) Clinical:
i) occurs primarily in older children and
young adults
ii) nephritic or nephrotic syndrome
iii) low levels of C3
iv) do not have postinfectious GN
v) no systemic inflammatory condition
vi) most progress to end-stage renal
failure, regardless of treatment !!

Membranoproliferati
Type I

NEPHRITIC SYNDROME

hematuria
oliguria
BUN and creatinine
hypertension
proteinuria (< 3.5 g/day); edema

Glomerulornephritis - INFLAMMATORY
Acute GN (post infectious GN)
a) sudden onset of nephritic syndrome
b) diffuse hypercellularity og glomeruli
c) most often associated with
i) group A -hemolytic streptococci
- S. pyogenes
ii) others less frequently
- staph
- spirochetes
- viruses
d) most often affect children
i) one of most common renal

Acute GN (post infectious GN)

e) latent period of ~ 10-14 days
f) diffuse enlargement and hypercellularity
of glomeruli, hypercellularity due to:
i) proliferation of endothelial and
mesangial cells and infiltration of
neutrophils and monocytes
g) characteristics:
i) subepithelial humps of GBM
ii) granular IgG and C3 along GBM
in association with humps

Acute GN (post infectious GN)

h) Clinical:
i) most resolve but in rare occasions can
progress to develop many crescents and renal
failure
ii) primary infection in pharynx or skin
iii) nephritic syndrome (abrupt)
- hematuria
- oliguria
- facial edema
- hypertension
iv) serum C3

Acute GN
(post infectious G

Clinical Features: G.Nephritis

Hypertension
Skin Infections
Congestive Cardiac Failure

Laboratory Features: G.Nephritis

Inflammation
Decreased filtration
Damage to filtration unit

:Diffuse Proliferative GN

Hyperplasia of epithelium

& endothelium.
Cell Swelling.
Inflammatory cells.
Obstruction to flow.
Enlarged hypercellular
glomeruli.

Normal

Proliferative
Post streptococal

IF- Diffuse Proliferative GN

Crescentic GN
a) ominous morphological pattern
i) majority of glomeruli are surrounded
by accumulation of cells in
Bowmans
capsule (parietal
epithelial cells)
ii) indicative of fulminant glomerular
damage and always leaves
scarring
iii) does not denote a specific etiologic

Crescentic
GN

b) most patients with substantial (~ 80%)

crescents progress to renal failure
c) Fibrin in Bowmans capsule is important
for the formation of glomerular
crescents
i) Tx with anticoagulants
d) associated with areas of segmental
necrosis within glomeruli

Crescentic GN
e) Types:
i) Type I anti-GBM antibody disease
(GOODPASTURE SYNDROME) or
idiopathic
-plasmapheresis to remove
circulating Ab is helpful in this type
of RPGN (i.e., crescentic)
-- etiology unknown

Crescentic GN
e) Types:
ii) Type II immune-complex mediated
disease
- can be complication of any of
the immune complex nephritides
SLE, IgA nephropathy,
HS Purpura
all these show granular pattern
(characteristic of immune complex)
- not helped with plasmapheresis

Crescentic GN
e) Types:
iii)

Type III pauci-immune type

- lack of anti-GBM Ab or immune complexes
- patients do have ANCA (~90%)
either c or p patterns
- in some cases, is a component of
vasculitides
(i.e., Wegener Granulomatosis)
f) clinical:
i) hematuria with red cell cast in urine
ii) transplant or chronic dialysis in most
patients

Crescentic GN

Crescentic GN - (RPGN)

Crescentic GN - (Trichrome Stain)

:Goodpasture Syndrome

Focal GN

a) only some of the glomeruli are involved

i) or to segments of the glomerulus
b) different from focal & segmental
glomerulosclerosis which is a
noninflammatory disease
i) glomeruli essentially
normocellular
c) many conditions produce this defect
i) primary renal disease or
systemic
diseases such as IgA
nephropathy
and Henoch-Schnlein

Focal GN
d) IgA nephropathy (Berger Disease)
i) association with chronic liver disease
- impaired capacity to remove circulating immune
complexes
ii) IgA and fibronectin found in > 70 % of IgA
nephropathy
patients.
iii) Ag involve bacterial, viral and dietary
- infectious agents is suggested from data
showing hematuria following upper respiratory or GI
infection !!
- dietary agents milk proteins in
mesangium; gluten-sensitivity

Focal
GN
d) IgA nephropathy (Berger Disease)

iv) C3 and properdin (via activation of

alternate pathway) usually present
together with IgA in mesangium
- C1q and C4 (classic pathway activation) are
typically absent
v) IgA nephropathy is a mesangial proliferative
lesion (granular deposits)

Focal
GN

d) IgA nephropathy (Berger Disease)

vi) clinical:
- common in young men (15-30)
- presents with hematuria
- nephrotic type proteinuria is uncommon
(may indicate more severe glomerular
damage)
- ~ 20 % of IgA nephropathy patients
progress to end-stage renal failure !!
- most common type of 1 GN in several
parts of the world (France, Italy, Japan,
Singapore and Austria) ~ 20 %.

Focal
GN
e) Henoch-Schnlein (HS) Purpura
i) close relationship with IgA
nephropathy
- differentiate: IgA purely renal;
HS is a systemic disease, etc.

IgA nephropathy
(Berger Disease

:Focal Segmental Gl. Sclerosis

Hereditary nephritis (Alport

syndrome)
a)most often present as recurrent
hematuria
b) structural defects in GBM
i) specific molecular defect affecting
type IV collagen
c) usually does not present with nephrotic
syndrome and proteinuria
d) more severe in men
i) die by age 40
e) progressive hearing loss (high
frequencies)
f) ocular defects most often the lens

Benign familial hematuria

(thin GBMdisease)
a) presents as recurrent hematuria in
childhood or young adults (similar to Alport
syndrome)
b) no progression to renal failure (unlike
Alport syndrome)
c) reduced thickness of GBM (capillary site)
d) one of most important causes of
asymptomatic
hematuria
e) IgA nephropathy and this disease are two
most
major diagnostic considerations of

The only place success

comes before work is in a
dictionary!