肾小球疾病
Glomerular Diseases
丁小强
复旦大学附属中山医院
Pathological changes
-- glomerular injury
Clinical manifestations
--proteinuria / hematuria
A group of diseases
Complicated causes & mechanisms
Various clinical manifestations
Different prognosis
Multiple treatment
? primary glomerular diseases
? secondary glomerular diseases
? hereditary glomerular diseases
Immune mechanisms
Humoral
Cell-mediated
Non-immune
mechanisms
Inflammation
Glomerular diseases
A,Immune mechanisms
(A)deposits of Circulating Immuno-Complex
(CIC)
circilation antigen+ antibody
CIC
kidney CIC/deposits
antigen
extrinsic
drugs--nonhomologous serum,penicillin
foods—xenogenic protein
pathogen—specific serotypes streptococci,
HBV,HCV
intrinsic
nucleus（ SLE)
cytoplasm（ ANCA）
cellular membrane
antigen of tumor
antigen of thyroid
Why does CIC deposit in the
glomeruli?
? Large area of glomerrular capillaries
--more chances to contact
? Net structure of CIC
--easy to deposit and settle down
? Clearance dysfunction of mesangial cells,
disability of mononuclear macrophage,
component or function defect of complements
Decrease clearance of CIC
(B)in situ Immunocomplex
1,Native renal antigen
glomerular basement membrane
+ anti- glomerular basement membrane
antibody
(anti- glomerular basement membrane
glomerulonephritis)
2,Antigens trapped or planted
DNA+ anti-DNA antibody
(Lupus Nephritis)
Balance between the deposit and
clearance of IC determines the
situation of the diseases
? Persistence of antigen
? Clearance dysfunction of mesangial cells
? disability of mononuclear macrophage
? component or function defect of
complements
IC deposit > clearance
B,Cell-mediated immune
mechanisms
minimal change glomerulopathy?
C,Non –immune mechanisms
? glomerular hypertension
? hyperlipidemia (LDL- Cho)
? advanced glycosylation end products
(protein)
glomerulosclerosis
Inflammation
? Mediators of inflammation
– A group of molecules which act as mediators
of inflammation and complicated biological
function
? Origin of inflammation mediators in
kidney
– Extrinsic Cells in kidney
? infiltrative neutrophil,lymphocyte,mononuclear
macrophage,platelet
– Intrinsic cells in kidney
? Mesangial cells,tubular cells,endothelial cells
Mediators of inflammation
- active oxygen and active nitrogen
- lipids
- complements
- cytokines
- chemotatic factors
- adhesion molecules
- growth factors
- vasoactive substances
To arouse or promote
- proliferation of cells
- accumulation of extracellular matrix
- changes of histological structure
- expression of immunomodulating
molecules and adhension molecules
Effects of the inflammation mediators
Mechanisms of Primary GN
immune non-immune
inflammation
Inflammatory cells
Extrinsic cells Intrinsic cells
neutrophil,lymphcyte mesangial cells
mononuclear macrophage epithelial cells
platelet,tubular cells endothelial cells
Inflammation mediators
cytokines TNF?,IL-1?
growth factors TGF?,PDGF
chemotatic factors MCP-1,IL-8
complements,vasoactive substances
active oxygen and active nitrogen
Coagulation and fibrolysis system,enzyme
Glomerular injuries
Essential in
the initiation
Essential in the
progressive period
immune non-immune
initiation end stage
Primary GN
Sites of pathological changes
Mesangium
Mesangial cell
Mesangial matrix
Basement membrane
Podocyte
Foot process
Endothelial cell
The peripheral
portion of a
glomerular
lobule
Pathological changes
? LM – Mesangial cells,matrix of mesangium
– Epithelial cells
– Endothelial cells
– Basement membrane
– Loops of glomeruli
? EM
– Foot process
– Basement membrane
– Hyperplasy of mesangium
(electron-dense deposits )
? IF
– Sites,appearances and types of the deposit
(Ig or C)
Basical changes
?Proliferation
?Fibrosis and sclerosis
?Necrosis
?Infiltration of inflammatory cells
Extents of Injuries
primary GN glomerular injuries—only
or dominating changes
secondary GN glomerular injuries— a
part of systematic diseases
diffuse impaired glomeruli>50%
focal impaired glomeruli <50%
global impaired capillary loops of
a glomerule >50%
segmental impaired capillary loops of
a glomerule <50%
Pathological types of primary GN
? Minimal change glomerulonephritis
? Focal segmental lesions
? Diffuse glomerulonephritis
? Unclassified glomerulonephritis
1,Minor Lesions of glomeruli
No specific lesions
LM—mild proliferation of mesangial cells
and accumulation of ECMS
? minimal change disease,MCD
? mild mesangial proliferative GN
? recovery stage of endocapillary GN
? others
MCD (left)normal,(right) fusion & effacement of foot processes
2,Focal and Segmental Lesions
1) focal and segmental proliferative
glomerulonephritis
2) focal and segmental glomerulosclerosis
segmental glomerulonephritis
3,Diffusive glomerulonephritis
(1) membranous nephropathy
－－ MN
(lesions in GBM)
MN (left) normal,(right)subepithelial deposits of IC(D),thickening
of GBM,formation of spikes (S),fusion of foot processes
(2) proliferative glomerulonephritis
? mesangial proliferative GN
( lesions in mesangium)
– IgA nephropathy
– Non-IgA nephropathy
? domonating IgG deposit
? IgM nephropathy
MsPGN (left)normal,(right)proliferation of mesangial cells
and matrix and electron-dense deposits (D)
? endocapillary proliferative GN
( lesions in mesangium &
endothelial cells)
endocapillary proliferative GN (left) normal,(right)
endothelial(E) & mesangial(M) cell proliferation and subepithelial
humplike dense deposits(D)
? mesangiocapillary GN
or
membranoproliferative GN
(lesions in mesangium & GBM)
? dense desposit GN
(electron-dense deposits)
MmPGN (left) normal,(right) proliferation of mesngium
(M),electron-dense deposits(D),and subendothelial mesangial
cytoplasm interposition（ I）
? crescentic GN
or
extracapillary GN
Crescentic GN (left) normal,(right) splitting of GBM,leakage of
fibrin(F),proliferation of epithelial cells,(E),infiltration of
mononuclear macrophages(P),formation of crescents
(3) sclerosing GN
4.unclassified glomerulonephritis
Characters of lesions in GN
Proliferative changes
MsPGN
IgAN
IgMN
Others
Including segmental proliferative GN
MmPGN
Crescentic GN
Endocapillary proliferative GN
Non- proliferative changes
FSGS
MCD
MN
?Proliferation of mesangium can
presents in varied types of GN
?Proliferation and subsequent
stiffness of mesangium may be the
results of varied types of GN
FSGS
? primary--later-phase of the disease
itself
? secondary-- later-phase of other
types of GN
?Crescents can presents in different
types of GN
Clinical manifestations
Proteinuria
– Urinary protein test — positive
– Urinary protein excretion rate
?150mg/d
Charge barrier of glomerule
1.Epithelial cells 2,GBM 3,Endothelial cells
4,Filtrated substances
Filtration barrier
mechanisms of production of proteinuria
机 制 性 质
肾小球滤过 肾小管重吸收 中、高分子 低分子
肾小球性
蛋白尿
肾小管性
蛋白尿
Moderate/high
MW molecules
mechanisms molecular wieghts
filtration from
Glomeruli
Readsorption
from tulules
Low MW
molecules
Glomerular
proteinuria
Tubular
proteinuria
filtration barrier
properties charge- size-
selective selective
Selective albumin impaired normal
proteinuria (moderate MW molecules)
Non-selective albumin &
proteinuria high MW proteins impaired impaired
* Mixed proteinuria,moderate/high MW or moderate/low
MW;glomerular &tubular proteinuris
quantity
Mild < 1.5g/d
Moderate 1.5-3.5g/d
severe > 3.5g/d或 50mg/kg/d
hematuria
? RBC >3个 /HP
(fresh,10 ml sample,1500rmp centrifuge
for 5 min,sediment observation)
? gross hematuria
Red color of urine,1ml blood /1L urine
hematuria
RBC from glomeruli
squeezing
through GBM
dismorphic RBC
Phase-contrast
microscopy
? dismorphic RBC>50％
Hypothesis:glomerular bleeding
? dismorphic RBC>70%
Final diagnosis:glomerular bleeding
Urinary RBC volume
distribution curve
?dissymmetry curve
?MCV of urinary
RBC<that in blood
changing when passing
tubules with different
osmosis
edema fluid retention in tissue spaces
peripheral edema
fluid retention in serous cavity
glomerular diseases
GFR? large amount of urinaryprotein lost
Intrinsic RAS & Aldosterone ? hypoalbuminemia
water & sodium filtration ? colloid osmotic pressure ?
water & sodium readsorption?
primary water & sodium retention secondary water & sodium retention
Effective circulation blood volumn?
edema
Effective circulation blood volumn ?
Hypertension
glomerular diseases
primary water & stimulus,such asischemia
sodium retention
Volumn-dependent vessoconstrictive vessodilatory
substances? substances?
RAS,Ald PGI2,PGE2
vessoactive substances-dependent
Hypertension
Clinical types of GN
? Glomerulonephropathy
? Confined concept
? leading manifestation,proteinuria,
with/without hematuria
? Extensive concept
? glomerular diseases ( disorders )
? Glomerulonephritis
? leading manifestation,hematuria,with/without
proteinuria
Nephrotic syndrome
1,Large-amount proteinuria > 3.5g/d
2,hypoalbuminemia < 30g/L
3,edema
4,hyperlipidemia
1+2 ---essential
severe edema hyperlipidemia
hypoalbuminemia
Large-amount
proteinuria
Center
key
Essential for
diagnosis
Intake of protein
Ingestion from GI
synthesis in liver
lost through urine
NS
consumption
Mechanisms of hypoalbuminemia
Clinical manifestation of GN
m a n i f e s t a t i o n
i n i t i a t i o n h e m a t u r i a p r o t e i n u r i a e d e m a,h y p e r t e n s i o n r e n a l f a i l u r e
急性G N 综合征 a c u t e 100% 100% f r e q u e n t resumable
急进性G N 综合征 a c u t e 100% 100% f r e q u e n t A R F
慢性G N 综合征 l a t e n t f r e q u e n t f r e q u e n t f r e q u e n t CRF
隐匿性G N 综合征* l a t e n t f r e q u e n t < 1 g / d (-) (-)
Linkage of clinical manifestation and
pathological changes (1)
Pathological proliferative non-proliferative
changes MsPGN MCD
MmPGN MN*
Endocapillary PGN FSGS
Crescentic GN
Clinical hematuria－ proteinuria－
certain certain,sometimes
Manifestation nephritis syndrome nephrotic syndrome
proteinuria－ hematuria－
possible occasional *
Linkage of clinical manifestation and
pathological changes (2)
clinical pathological
AGN endocapillary PGN
possible NS
RPGN crescentic GN
possible NS
CGN
nephritis syndrome MsPGN 2
MmPGN 2
nephritis syndrome FSGS 2
+nephrotic syndrome MN2
NS MCD 1
Acute Glomerulonephritis
Etiology
? Streptococcus ?-hemolytic streptococcus,
group A,type XII,nephritogenic strains
?antigen
?components of cytoplasm & membrane
?frequently CIC,sometimes ‘planted
antigen’
? Others
? other bacteria,such as staphylococcus epidermidis
? viruses
? parasites
Pathological changes
? Endocapillary Proliferative GN
? Acute phase
? Proliferation of endothelial &
mesangium
? Recovery phase
? Only mesangium proliferation,
sometimes minor lesion
Clinical Manifestation
1.Epidemiology,primarily children,
sometimes adults & the aged
2,Preliminary infection
? frequently tonsillitis,upper respiratory
infection
?Latent period:1-3 w
? occasionally skin infection
?Latent period:longer,but less than 4w
3.Nephritis syndrome
(1)hematuria
100%,40% are gross hematuria
(2)proteinuria
frequent,<20% are nephrotic syndrome
(3)edema >90%
(4)hypertension 80%
(5)renal failure
mild,acute renal failure
4.Laboratory findings
(1) acute phase of infection of Strep,
?elevated ASO titer (some Strep,No hemolysin O)
?only the marker of infection,not
nephritis
(2) acute phase of immune reactions
?serum C3 & total complements?,return to
normal within 8w
?blood CIC?
Natural History
? edema and hypertension
– disappear in one month
? hematuria,proteinuria
– usually reduce in one month,resolve within
2 to 3 months
– some resolve within 6 to 12 months
? C3
– return to normal in two months
Diagnosis
Points
? preliminary infection &latent period
? acute onset
? surely hematuria,frequently edema and
hypertension
? ASO ?,C3 ? —— dynamic change
? Self-limitation
Differential Diagnosis
Diseases presented with acute nephritis
syndrome
? GN secondary to infection of other pathogens
– other bacteria,viruses (Varicella-zoster virus,EB,
influenza virus)
– Climax of infection or within 5 days
– Mild abnormal of urine examination
– Hypertension and edema are unusual
– Normal blood complement level
? rapidly progressive GN
? CGN
? systemic diseases
lupus nephritis
Sch?nlein-Henoch purpura
Indications of kidney biopsy
? Oligouria > 1w,except ECBV
insufficient,urinary tract obstruction,etc
? Progressive renal failure
? Unresolved in 2 months
? untypical manifestation,or with
nephrotic syndrome
Treatment
1.Supportive treatment
? Rest
? Food & water
?Restrictive intake of
?NaCl <5 g/d
? if moderate to severe edema or hypertension
?Water
? if decreased urine volume
?Protein
? Renal failure,but not dialysis yet
2.Treatment of infection
? Penicilin for 2 w
? Tonsillectomy– if recurrent attacks
of tonsillitis
1) patient’s condition is stable,
Upro<1g/d,URBC < 10/HP
2) Penicilin for 2 wks before and after
the surgery
3,Symptomatic treatment
? Diuresis
? Antihypertension
? Dialysis
Prognosis
? hematuria,proteinuria
–usually reduce in one month,resolve
within 2 to 3 months
–some resolve within 6 to 12 months
? 1%ARF ? Death
? 6%-18% ? CGN?
Rapidly progressive glomerulonephritis
RPGN
?Rapidly progressive nephritis syndrome
?Some induced by respiratory infection
?Acute onset,rapidly progressive
?Renal failure within a few weeks to a few
months
1.primary RPGN Crescentic GN
2.other primary GN other pathological
changes with lots
of crescents
3.secondary RPGN SLE,SHP,etc
RPGN
Type I Type II Type III
anti-GBM IC Pauci-immune
IF linear GBM Granular GBM （ -）
deposits & mesangium
deposits
anti-GBM AB（ +） C3?,CIC? 70%-80%
small vessel vasculitis
ANCA （ +）
the young & the middle-aged the middle-aged
middle aged & aged & aged
Most frequently in China
Diagnosis
? Acute onset
? Rapidly progressive
? Renal failure within a few weeks to a few
months
? Acute renal failure Chronic renal failure
Differential Diagnosis
Rapidly progressive nephritis syndrome
——not primary RPGN
- other primary GN
AGN,IgAN,etc
- secondary GN
Goodpasture Syndrome,
LN,SHP
* accompanied by crescentic GN
* severe pathological changes
Diseases with ARF
? ATN
? AIN
- definite etiology
-obsolete proteinuria and hematuria
- specific manifestation
ATN—— large quantity of renal tubular
epithelial cells in urine
AIN—— hypersensitiveness (rashes,fever,
arthralgia)
Treatment EARLY!!!
? Aim to humoral immune mechanisms
1.plasmapheresis discard the antibodies
plasm exchange
immoadsorption
type I,III
2.drugs glucocorticoid +cytotoxic drugs
MP0.5-1.0g/d?3,repeat if necessary
CTX
type II,III
symptomatic treatment
? renal failure
– balance of fluid,electrolytes and acid-base
– dialysis
? infection
? hypertension
Prognosis
Hardly relieve
most?CRF or death
Risk factors
Type I-worst,II-worse,III-bad
Treatment not progressive & prompt
Age the aged
Chronic Glomerulonephritis
Manifestation chronic nephritis syndrome
Pathological changes except MCD,MmPGN,
Crescentic GN
Clinical manifestation
1.age any age,frequently young
2.preliminary infection
upper respiratory tract,
intestinal tract
latent period < 1 wk
3.nephritis syndrome
Hematuria,proteinuria,edema
Hypertension,renal failure
uremia
4.Prognosis factors
(1)pathological properties
(2)treatment
(3)hypertension
(4)infection,prerenal factors
(hypotension etc)
(5)nephrotoxic drugs
Points of Diagnosis
? chronic onset
? proteinuria and/or hematuria
? protracted and progressive
Differential
Diagnosis
CGN
Differential Diagnosis
1,AGN
AGN CGN
age children young&middle-aged
preliminary infection
frequently sometimes
latent period 1-3w <1w
onset acute chronic,insidious
hematuria 100% sometimes no
edema frequently sometimes no
hypertension frequently sometimes no
ASO frequently ? normal
blood C3 frequently ?,persistent?/normal
return within 8wks
prognosis resolved within 1yr protracted and
progressive
pathology MmPGN/MsPGN
2.Essential hypertensive nephrosclerosis
EHT CGN
first present hypertension abnormal urine
function injury in advance
tubule glomerule
hematuria occasionally frequently
nephrotic proteinuria
occasionally frequently
systemic hypertension manifestation
heart,eyeground compared with kidney
equal milder
pathology arteriolar sclerosis
3.secondary GN
SLE
(1)systemic presentation
(2)immune abnormolity(C,self-AB)
(3)pathological changes
SHP
(1)purpura
(2)stomach,joint
Chronic pyelonephritis
CPN CGN
mechanisms infection immune
sites pelvis,calices,tubule glomerule
presents of infection + ?
Upro excretive /tubular glomerular
URBC non-glomerular glomerular
hypertension infrequently frequently
edema infrequently frequently
kidney lesions tubule glomerule
dysmorphosis one side two side
Treatment
Target inhibit immune reaction
halt the progression of disease
1.restrictive intake of protein
<0.5-0.8g/kg/d
protein of high biological value
?pressure in glomeruli
2.Antihypertension
less than 140/90mmHg,
ideal target 125/83mmHg
dialation of efferent glomerular
arteriole > dialation of afferent
glomerular arteriole
pressure in glomeruli? Upro?
postpone glomerulosclerosis
ACEI/ARB
3.anti-platelet
4.immunosupression
Clinical manifestation
1.Characteristics
(1)large quantity of Upro
(2)severe edema
(3)hypoalbuminemia
(4)hyperlipidemia
Nephrotic Syndrome
2.Others
(1) thrombosis & embolism
renal veins or inferior vena cava 25%
(2)infection
(3)acute renal failure
?Blood volume??perfusion of kidneys?
?ischemia of kidneys,tubule necrosis
?Severe glomerular lesions
?crescent formation
?Severe proliferation of mesangium
?Necrosis of capillary loops
?Nephrotoxic drugs
?idiopathetic
1.among varied types of pathology
2.between secondary GN
（ 1） SLE
（ 2） SHP
（ 3） DN history,hematuria,pathological changes
（ 4） amyloidosis
history of chronic infection,systemic lesions (heart,
liver,GI,tongue),pathological changes (kidney,
tongue,rectum)
（ 5） MM
Middle-aged/aged,ostalgia,osteonecrosis(X-ray,
isotope scanning),abnormal protein (blood single-
peak protein,blood and urine light chain
protein,urine BJ protein)
Diagnosis & Differential Diagnosis
1,Supportive treatment
1,rest
2,Food and water
(1) water & sodium
restriction when with severe edema
(2) protein 1-1.2g/kg/d
(3) lipid restriction when with hypoalbuminemia
(4) energy 30-35 Kal/kg/d
TREATMENT
2,symptomatic treatment
1,diuresis
osmotic diuretics
plasma colloid osmotic pressure ? tubule fluid osmotic pressure?
fluid transmit from tissue readsorption of water ?
space to blood vessels
blood volume ?
diuretics
mannitol,dextran,albumin
diuresis
2,Aim to proteinuria
ACEI/ARB
3,Major treatment
1,glucocorticoid
mechanisms (1)immuosupression
(2)anti-inflammation
principles (1)sufficient dose when initiation
0.8-1.2g/kg/d
reduce 2wks after Upro is negative
*if Upro doesn’t reduced apparently
in 8-12wks?ineffective
(2) reduce the dose slowly
?10%/2-3wks
(3) sustaining treatment
minimal dose:10-15mg/d,>6m-1y
Sensitivity of glucocorticoid
1mg/kg/d ? 8w
negative Upro positive
relapse when reduce to some dosage
sensitive
dependent
ineffective
2,immunosuppressive agents
? cytotoxic drugs
alkylating agent—CTX,chlormethine,CB1348
inhibit duplication of DNA
? Aza,MMF
inhibit synthesis of RNA
inhibit proliferation of B lymphocyte
? CyA inhibit synthesis of L-2
inhibit proliferation of T lymphocyte
indications
? glucocorticoid dependent or ineffective
? glucocorticoid untolerated
4,Treatment of complications
? anticoagulation,thrombolysis
? anti-infection
? balance of electrolyte
Glomerular Diseases
丁小强
复旦大学附属中山医院
Pathological changes
-- glomerular injury
Clinical manifestations
--proteinuria / hematuria
A group of diseases
Complicated causes & mechanisms
Various clinical manifestations
Different prognosis
Multiple treatment
? primary glomerular diseases
? secondary glomerular diseases
? hereditary glomerular diseases
Immune mechanisms
Humoral
Cell-mediated
Non-immune
mechanisms
Inflammation
Glomerular diseases
A,Immune mechanisms
(A)deposits of Circulating Immuno-Complex
(CIC)
circilation antigen+ antibody
CIC
kidney CIC/deposits
antigen
extrinsic
drugs--nonhomologous serum,penicillin
foods—xenogenic protein
pathogen—specific serotypes streptococci,
HBV,HCV
intrinsic
nucleus（ SLE)
cytoplasm（ ANCA）
cellular membrane
antigen of tumor
antigen of thyroid
Why does CIC deposit in the
glomeruli?
? Large area of glomerrular capillaries
--more chances to contact
? Net structure of CIC
--easy to deposit and settle down
? Clearance dysfunction of mesangial cells,
disability of mononuclear macrophage,
component or function defect of complements
Decrease clearance of CIC
(B)in situ Immunocomplex
1,Native renal antigen
glomerular basement membrane
+ anti- glomerular basement membrane
antibody
(anti- glomerular basement membrane
glomerulonephritis)
2,Antigens trapped or planted
DNA+ anti-DNA antibody
(Lupus Nephritis)
Balance between the deposit and
clearance of IC determines the
situation of the diseases
? Persistence of antigen
? Clearance dysfunction of mesangial cells
? disability of mononuclear macrophage
? component or function defect of
complements
IC deposit > clearance
B,Cell-mediated immune
mechanisms
minimal change glomerulopathy?
C,Non –immune mechanisms
? glomerular hypertension
? hyperlipidemia (LDL- Cho)
? advanced glycosylation end products
(protein)
glomerulosclerosis
Inflammation
? Mediators of inflammation
– A group of molecules which act as mediators
of inflammation and complicated biological
function
? Origin of inflammation mediators in
kidney
– Extrinsic Cells in kidney
? infiltrative neutrophil,lymphocyte,mononuclear
macrophage,platelet
– Intrinsic cells in kidney
? Mesangial cells,tubular cells,endothelial cells
Mediators of inflammation
- active oxygen and active nitrogen
- lipids
- complements
- cytokines
- chemotatic factors
- adhesion molecules
- growth factors
- vasoactive substances
To arouse or promote
- proliferation of cells
- accumulation of extracellular matrix
- changes of histological structure
- expression of immunomodulating
molecules and adhension molecules
Effects of the inflammation mediators
Mechanisms of Primary GN
immune non-immune
inflammation
Inflammatory cells
Extrinsic cells Intrinsic cells
neutrophil,lymphcyte mesangial cells
mononuclear macrophage epithelial cells
platelet,tubular cells endothelial cells
Inflammation mediators
cytokines TNF?,IL-1?
growth factors TGF?,PDGF
chemotatic factors MCP-1,IL-8
complements,vasoactive substances
active oxygen and active nitrogen
Coagulation and fibrolysis system,enzyme
Glomerular injuries
Essential in
the initiation
Essential in the
progressive period
immune non-immune
initiation end stage
Primary GN
Sites of pathological changes
Mesangium
Mesangial cell
Mesangial matrix
Basement membrane
Podocyte
Foot process
Endothelial cell
The peripheral
portion of a
glomerular
lobule
Pathological changes
? LM – Mesangial cells,matrix of mesangium
– Epithelial cells
– Endothelial cells
– Basement membrane
– Loops of glomeruli
? EM
– Foot process
– Basement membrane
– Hyperplasy of mesangium
(electron-dense deposits )
? IF
– Sites,appearances and types of the deposit
(Ig or C)
Basical changes
?Proliferation
?Fibrosis and sclerosis
?Necrosis
?Infiltration of inflammatory cells
Extents of Injuries
primary GN glomerular injuries—only
or dominating changes
secondary GN glomerular injuries— a
part of systematic diseases
diffuse impaired glomeruli>50%
focal impaired glomeruli <50%
global impaired capillary loops of
a glomerule >50%
segmental impaired capillary loops of
a glomerule <50%
Pathological types of primary GN
? Minimal change glomerulonephritis
? Focal segmental lesions
? Diffuse glomerulonephritis
? Unclassified glomerulonephritis
1,Minor Lesions of glomeruli
No specific lesions
LM—mild proliferation of mesangial cells
and accumulation of ECMS
? minimal change disease,MCD
? mild mesangial proliferative GN
? recovery stage of endocapillary GN
? others
MCD (left)normal,(right) fusion & effacement of foot processes
2,Focal and Segmental Lesions
1) focal and segmental proliferative
glomerulonephritis
2) focal and segmental glomerulosclerosis
segmental glomerulonephritis
3,Diffusive glomerulonephritis
(1) membranous nephropathy
－－ MN
(lesions in GBM)
MN (left) normal,(right)subepithelial deposits of IC(D),thickening
of GBM,formation of spikes (S),fusion of foot processes
(2) proliferative glomerulonephritis
? mesangial proliferative GN
( lesions in mesangium)
– IgA nephropathy
– Non-IgA nephropathy
? domonating IgG deposit
? IgM nephropathy
MsPGN (left)normal,(right)proliferation of mesangial cells
and matrix and electron-dense deposits (D)
? endocapillary proliferative GN
( lesions in mesangium &
endothelial cells)
endocapillary proliferative GN (left) normal,(right)
endothelial(E) & mesangial(M) cell proliferation and subepithelial
humplike dense deposits(D)
? mesangiocapillary GN
or
membranoproliferative GN
(lesions in mesangium & GBM)
? dense desposit GN
(electron-dense deposits)
MmPGN (left) normal,(right) proliferation of mesngium
(M),electron-dense deposits(D),and subendothelial mesangial
cytoplasm interposition（ I）
? crescentic GN
or
extracapillary GN
Crescentic GN (left) normal,(right) splitting of GBM,leakage of
fibrin(F),proliferation of epithelial cells,(E),infiltration of
mononuclear macrophages(P),formation of crescents
(3) sclerosing GN
4.unclassified glomerulonephritis
Characters of lesions in GN
Proliferative changes
MsPGN
IgAN
IgMN
Others
Including segmental proliferative GN
MmPGN
Crescentic GN
Endocapillary proliferative GN
Non- proliferative changes
FSGS
MCD
MN
?Proliferation of mesangium can
presents in varied types of GN
?Proliferation and subsequent
stiffness of mesangium may be the
results of varied types of GN
FSGS
? primary--later-phase of the disease
itself
? secondary-- later-phase of other
types of GN
?Crescents can presents in different
types of GN
Clinical manifestations
Proteinuria
– Urinary protein test — positive
– Urinary protein excretion rate
?150mg/d
Charge barrier of glomerule
1.Epithelial cells 2,GBM 3,Endothelial cells
4,Filtrated substances
Filtration barrier
mechanisms of production of proteinuria
机 制 性 质
肾小球滤过 肾小管重吸收 中、高分子 低分子
肾小球性
蛋白尿
肾小管性
蛋白尿
Moderate/high
MW molecules
mechanisms molecular wieghts
filtration from
Glomeruli
Readsorption
from tulules
Low MW
molecules
Glomerular
proteinuria
Tubular
proteinuria
filtration barrier
properties charge- size-
selective selective
Selective albumin impaired normal
proteinuria (moderate MW molecules)
Non-selective albumin &
proteinuria high MW proteins impaired impaired
* Mixed proteinuria,moderate/high MW or moderate/low
MW;glomerular &tubular proteinuris
quantity
Mild < 1.5g/d
Moderate 1.5-3.5g/d
severe > 3.5g/d或 50mg/kg/d
hematuria
? RBC >3个 /HP
(fresh,10 ml sample,1500rmp centrifuge
for 5 min,sediment observation)
? gross hematuria
Red color of urine,1ml blood /1L urine
hematuria
RBC from glomeruli
squeezing
through GBM
dismorphic RBC
Phase-contrast
microscopy
? dismorphic RBC>50％
Hypothesis:glomerular bleeding
? dismorphic RBC>70%
Final diagnosis:glomerular bleeding
Urinary RBC volume
distribution curve
?dissymmetry curve
?MCV of urinary
RBC<that in blood
changing when passing
tubules with different
osmosis
edema fluid retention in tissue spaces
peripheral edema
fluid retention in serous cavity
glomerular diseases
GFR? large amount of urinaryprotein lost
Intrinsic RAS & Aldosterone ? hypoalbuminemia
water & sodium filtration ? colloid osmotic pressure ?
water & sodium readsorption?
primary water & sodium retention secondary water & sodium retention
Effective circulation blood volumn?
edema
Effective circulation blood volumn ?
Hypertension
glomerular diseases
primary water & stimulus,such asischemia
sodium retention
Volumn-dependent vessoconstrictive vessodilatory
substances? substances?
RAS,Ald PGI2,PGE2
vessoactive substances-dependent
Hypertension
Clinical types of GN
? Glomerulonephropathy
? Confined concept
? leading manifestation,proteinuria,
with/without hematuria
? Extensive concept
? glomerular diseases ( disorders )
? Glomerulonephritis
? leading manifestation,hematuria,with/without
proteinuria
Nephrotic syndrome
1,Large-amount proteinuria > 3.5g/d
2,hypoalbuminemia < 30g/L
3,edema
4,hyperlipidemia
1+2 ---essential
severe edema hyperlipidemia
hypoalbuminemia
Large-amount
proteinuria
Center
key
Essential for
diagnosis
Intake of protein
Ingestion from GI
synthesis in liver
lost through urine
NS
consumption
Mechanisms of hypoalbuminemia
Clinical manifestation of GN
m a n i f e s t a t i o n
i n i t i a t i o n h e m a t u r i a p r o t e i n u r i a e d e m a,h y p e r t e n s i o n r e n a l f a i l u r e
急性G N 综合征 a c u t e 100% 100% f r e q u e n t resumable
急进性G N 综合征 a c u t e 100% 100% f r e q u e n t A R F
慢性G N 综合征 l a t e n t f r e q u e n t f r e q u e n t f r e q u e n t CRF
隐匿性G N 综合征* l a t e n t f r e q u e n t < 1 g / d (-) (-)
Linkage of clinical manifestation and
pathological changes (1)
Pathological proliferative non-proliferative
changes MsPGN MCD
MmPGN MN*
Endocapillary PGN FSGS
Crescentic GN
Clinical hematuria－ proteinuria－
certain certain,sometimes
Manifestation nephritis syndrome nephrotic syndrome
proteinuria－ hematuria－
possible occasional *
Linkage of clinical manifestation and
pathological changes (2)
clinical pathological
AGN endocapillary PGN
possible NS
RPGN crescentic GN
possible NS
CGN
nephritis syndrome MsPGN 2
MmPGN 2
nephritis syndrome FSGS 2
+nephrotic syndrome MN2
NS MCD 1
Acute Glomerulonephritis
Etiology
? Streptococcus ?-hemolytic streptococcus,
group A,type XII,nephritogenic strains
?antigen
?components of cytoplasm & membrane
?frequently CIC,sometimes ‘planted
antigen’
? Others
? other bacteria,such as staphylococcus epidermidis
? viruses
? parasites
Pathological changes
? Endocapillary Proliferative GN
? Acute phase
? Proliferation of endothelial &
mesangium
? Recovery phase
? Only mesangium proliferation,
sometimes minor lesion
Clinical Manifestation
1.Epidemiology,primarily children,
sometimes adults & the aged
2,Preliminary infection
? frequently tonsillitis,upper respiratory
infection
?Latent period:1-3 w
? occasionally skin infection
?Latent period:longer,but less than 4w
3.Nephritis syndrome
(1)hematuria
100%,40% are gross hematuria
(2)proteinuria
frequent,<20% are nephrotic syndrome
(3)edema >90%
(4)hypertension 80%
(5)renal failure
mild,acute renal failure
4.Laboratory findings
(1) acute phase of infection of Strep,
?elevated ASO titer (some Strep,No hemolysin O)
?only the marker of infection,not
nephritis
(2) acute phase of immune reactions
?serum C3 & total complements?,return to
normal within 8w
?blood CIC?
Natural History
? edema and hypertension
– disappear in one month
? hematuria,proteinuria
– usually reduce in one month,resolve within
2 to 3 months
– some resolve within 6 to 12 months
? C3
– return to normal in two months
Diagnosis
Points
? preliminary infection &latent period
? acute onset
? surely hematuria,frequently edema and
hypertension
? ASO ?,C3 ? —— dynamic change
? Self-limitation
Differential Diagnosis
Diseases presented with acute nephritis
syndrome
? GN secondary to infection of other pathogens
– other bacteria,viruses (Varicella-zoster virus,EB,
influenza virus)
– Climax of infection or within 5 days
– Mild abnormal of urine examination
– Hypertension and edema are unusual
– Normal blood complement level
? rapidly progressive GN
? CGN
? systemic diseases
lupus nephritis
Sch?nlein-Henoch purpura
Indications of kidney biopsy
? Oligouria > 1w,except ECBV
insufficient,urinary tract obstruction,etc
? Progressive renal failure
? Unresolved in 2 months
? untypical manifestation,or with
nephrotic syndrome
Treatment
1.Supportive treatment
? Rest
? Food & water
?Restrictive intake of
?NaCl <5 g/d
? if moderate to severe edema or hypertension
?Water
? if decreased urine volume
?Protein
? Renal failure,but not dialysis yet
2.Treatment of infection
? Penicilin for 2 w
? Tonsillectomy– if recurrent attacks
of tonsillitis
1) patient’s condition is stable,
Upro<1g/d,URBC < 10/HP
2) Penicilin for 2 wks before and after
the surgery
3,Symptomatic treatment
? Diuresis
? Antihypertension
? Dialysis
Prognosis
? hematuria,proteinuria
–usually reduce in one month,resolve
within 2 to 3 months
–some resolve within 6 to 12 months
? 1%ARF ? Death
? 6%-18% ? CGN?
Rapidly progressive glomerulonephritis
RPGN
?Rapidly progressive nephritis syndrome
?Some induced by respiratory infection
?Acute onset,rapidly progressive
?Renal failure within a few weeks to a few
months
1.primary RPGN Crescentic GN
2.other primary GN other pathological
changes with lots
of crescents
3.secondary RPGN SLE,SHP,etc
RPGN
Type I Type II Type III
anti-GBM IC Pauci-immune
IF linear GBM Granular GBM （ -）
deposits & mesangium
deposits
anti-GBM AB（ +） C3?,CIC? 70%-80%
small vessel vasculitis
ANCA （ +）
the young & the middle-aged the middle-aged
middle aged & aged & aged
Most frequently in China
Diagnosis
? Acute onset
? Rapidly progressive
? Renal failure within a few weeks to a few
months
? Acute renal failure Chronic renal failure
Differential Diagnosis
Rapidly progressive nephritis syndrome
——not primary RPGN
- other primary GN
AGN,IgAN,etc
- secondary GN
Goodpasture Syndrome,
LN,SHP
* accompanied by crescentic GN
* severe pathological changes
Diseases with ARF
? ATN
? AIN
- definite etiology
-obsolete proteinuria and hematuria
- specific manifestation
ATN—— large quantity of renal tubular
epithelial cells in urine
AIN—— hypersensitiveness (rashes,fever,
arthralgia)
Treatment EARLY!!!
? Aim to humoral immune mechanisms
1.plasmapheresis discard the antibodies
plasm exchange
immoadsorption
type I,III
2.drugs glucocorticoid +cytotoxic drugs
MP0.5-1.0g/d?3,repeat if necessary
CTX
type II,III
symptomatic treatment
? renal failure
– balance of fluid,electrolytes and acid-base
– dialysis
? infection
? hypertension
Prognosis
Hardly relieve
most?CRF or death
Risk factors
Type I-worst,II-worse,III-bad
Treatment not progressive & prompt
Age the aged
Chronic Glomerulonephritis
Manifestation chronic nephritis syndrome
Pathological changes except MCD,MmPGN,
Crescentic GN
Clinical manifestation
1.age any age,frequently young
2.preliminary infection
upper respiratory tract,
intestinal tract
latent period < 1 wk
3.nephritis syndrome
Hematuria,proteinuria,edema
Hypertension,renal failure
uremia
4.Prognosis factors
(1)pathological properties
(2)treatment
(3)hypertension
(4)infection,prerenal factors
(hypotension etc)
(5)nephrotoxic drugs
Points of Diagnosis
? chronic onset
? proteinuria and/or hematuria
? protracted and progressive
Differential
Diagnosis
CGN
Differential Diagnosis
1,AGN
AGN CGN
age children young&middle-aged
preliminary infection
frequently sometimes
latent period 1-3w <1w
onset acute chronic,insidious
hematuria 100% sometimes no
edema frequently sometimes no
hypertension frequently sometimes no
ASO frequently ? normal
blood C3 frequently ?,persistent?/normal
return within 8wks
prognosis resolved within 1yr protracted and
progressive
pathology MmPGN/MsPGN
2.Essential hypertensive nephrosclerosis
EHT CGN
first present hypertension abnormal urine
function injury in advance
tubule glomerule
hematuria occasionally frequently
nephrotic proteinuria
occasionally frequently
systemic hypertension manifestation
heart,eyeground compared with kidney
equal milder
pathology arteriolar sclerosis
3.secondary GN
SLE
(1)systemic presentation
(2)immune abnormolity(C,self-AB)
(3)pathological changes
SHP
(1)purpura
(2)stomach,joint
Chronic pyelonephritis
CPN CGN
mechanisms infection immune
sites pelvis,calices,tubule glomerule
presents of infection + ?
Upro excretive /tubular glomerular
URBC non-glomerular glomerular
hypertension infrequently frequently
edema infrequently frequently
kidney lesions tubule glomerule
dysmorphosis one side two side
Treatment
Target inhibit immune reaction
halt the progression of disease
1.restrictive intake of protein
<0.5-0.8g/kg/d
protein of high biological value
?pressure in glomeruli
2.Antihypertension
less than 140/90mmHg,
ideal target 125/83mmHg
dialation of efferent glomerular
arteriole > dialation of afferent
glomerular arteriole
pressure in glomeruli? Upro?
postpone glomerulosclerosis
ACEI/ARB
3.anti-platelet
4.immunosupression
Clinical manifestation
1.Characteristics
(1)large quantity of Upro
(2)severe edema
(3)hypoalbuminemia
(4)hyperlipidemia
Nephrotic Syndrome
2.Others
(1) thrombosis & embolism
renal veins or inferior vena cava 25%
(2)infection
(3)acute renal failure
?Blood volume??perfusion of kidneys?
?ischemia of kidneys,tubule necrosis
?Severe glomerular lesions
?crescent formation
?Severe proliferation of mesangium
?Necrosis of capillary loops
?Nephrotoxic drugs
?idiopathetic
1.among varied types of pathology
2.between secondary GN
（ 1） SLE
（ 2） SHP
（ 3） DN history,hematuria,pathological changes
（ 4） amyloidosis
history of chronic infection,systemic lesions (heart,
liver,GI,tongue),pathological changes (kidney,
tongue,rectum)
（ 5） MM
Middle-aged/aged,ostalgia,osteonecrosis(X-ray,
isotope scanning),abnormal protein (blood single-
peak protein,blood and urine light chain
protein,urine BJ protein)
Diagnosis & Differential Diagnosis
1,Supportive treatment
1,rest
2,Food and water
(1) water & sodium
restriction when with severe edema
(2) protein 1-1.2g/kg/d
(3) lipid restriction when with hypoalbuminemia
(4) energy 30-35 Kal/kg/d
TREATMENT
2,symptomatic treatment
1,diuresis
osmotic diuretics
plasma colloid osmotic pressure ? tubule fluid osmotic pressure?
fluid transmit from tissue readsorption of water ?
space to blood vessels
blood volume ?
diuretics
mannitol,dextran,albumin
diuresis
2,Aim to proteinuria
ACEI/ARB
3,Major treatment
1,glucocorticoid
mechanisms (1)immuosupression
(2)anti-inflammation
principles (1)sufficient dose when initiation
0.8-1.2g/kg/d
reduce 2wks after Upro is negative
*if Upro doesn’t reduced apparently
in 8-12wks?ineffective
(2) reduce the dose slowly
?10%/2-3wks
(3) sustaining treatment
minimal dose:10-15mg/d,>6m-1y
Sensitivity of glucocorticoid
1mg/kg/d ? 8w
negative Upro positive
relapse when reduce to some dosage
sensitive
dependent
ineffective
2,immunosuppressive agents
? cytotoxic drugs
alkylating agent—CTX,chlormethine,CB1348
inhibit duplication of DNA
? Aza,MMF
inhibit synthesis of RNA
inhibit proliferation of B lymphocyte
? CyA inhibit synthesis of L-2
inhibit proliferation of T lymphocyte
indications
? glucocorticoid dependent or ineffective
? glucocorticoid untolerated
4,Treatment of complications
? anticoagulation,thrombolysis
? anti-infection
? balance of electrolyte
