24 glomerular disease

Department of Nephrology, the First Affiliated Hospital Department of Nephrology, the First Affiliated Hospital Sun Yat-sun UniversitySun Yat-sun University

Qiongqiong Yang Qiongqiong Yang 杨琼琼杨琼琼

Glomerular disease

Glomerular diseaseGlomerular disease

a group of diseases characterized by similar clincal manifestations ：Proteinuria Hematuria Edema

Hypertension Etiology Pathogenesis Prognosis

： Different

outlineoutline

Anatomy and functionGeneral pathogenesisClinical syndromes and presentationSpecific glomerular diseases

Anatomy and functionAnatomy and function

Anatomy

•Retroperitoneally posterior part of the abdomen

•Either side of the vertebral column

•Right kidney is one vertebral body lower than the left.

Anatomy

Renal FunctionRenal FunctionRenal FunctionRenal Function

Remove wastesMaintain homeostasisSecrete EPO

Diagram of a bisected kidney

Anatomy-nephron

•Functional unit of kidney

•Renal corpuscle( 肾小体 ): Glomerulus, Bowman’s Capsule

• Renal tubule (Proximal tubule, Loop of Henle, Distal tubule, Collecting duct)

Three-dimensional schematic drawing of the glomerulus

Afferent arteriole

Efferent arteriole

Bowman’s Capsule

Basement membrane

Visceral Epithelium(Podocyte)

Parietal Epithelium

Capillary loops

Bowman’s Space

Endothelial cells

Stucture of renal glomerulus

Stucture of renal glomerulus

Mesangial matrix and cell

Ultramicroscopic Stucture of glomerullar Capillaries

Filtration Mem

Light micrograph of glomerulus

•Normal celluarity;

•Patent capillary lumens

Glomerular AnatomyGlomerular Anatomy

Capillary Lumen

Endothelial cell

Glomerularbasementmembrane

Epithelialcell

Podocytes

Electron micrograph

Capillary Lumen毛细血管腔

Endothelial cell内皮细胞

Ultrastructure of normal glomerular capillary

系膜细胞系膜基质

内皮细胞

上皮细胞足突

General pathogenesisGeneral pathogenesis

What causesglomerular disease ?

Most are of immunologic origin, and

caused by immune complexes !

• metabolic stress: DN

• mechanical stress:

• hypertension

Antibody mediated GN -Antibody mediated GN - Circulating Immune complex Circulating Immune complex

Location: Mesangial and sub-endothelial

Antibody mediated GN -Antibody mediated GN -

In-situ Immune complex In-situ Immune complex

Location: GBM sub-epithelial

• circulating auto antibodies with intrinsic autoantigens (component of normal parenchyma)

Antibody mediated GN - In-situ Immune Antibody mediated GN - In-situ Immune complex (trapped Ag)complex (trapped Ag)

Location: GBM sub-epithelial

Extrinsic antigens planted within the glomerulus

PathogenesisPathogenesis

In situ immune complex

Circulating immune complex

Activation of T lymphocytes

Acitvation of complements

cytokinesC5b-9 C5a,C3a

Epithelial, mesangial,

Endothelial cells

Macrophagepolynuclear leucocyte, platelets

polynuclear leucocyte, platelets

Mesangial cells

oxidative stress, protease, matrix accumulations

Glomerular Disease

Characterizations of glomerular Characterizations of glomerular diseasedisease ？？

Glomerular Filtration BarrierGlomerular Filtration Barrier

Glomerular Filtration Barrier InjuryGlomerular Filtration Barrier Injury

Fusion of foot process : ProteinuriaGBM Injury : Hematuria/ Proteinuria

Characteristics of Glomerular Diseases

Parameter Glomerular Tubulointerstitial

Proteinuria

MW of Protein

Renal morphology

RBC Morphology

Massive>++

>1.5~2.0g/d

Large/Medium/Small

Symmetry

dysmorphic

Small amount<2+

<1.0g/d

Small

Asymmetry

normal

HematuriaHematuria

Isomorphic nonglomerular erythrocytes. The arrows indicate the so-called crenated erythrocytes皱缩红细胞 , which are a frequent finding in nonglomerular hematuria.

Dysmorphic glomerular erythrocytes. The dysmorphism consists mainly in irregularities of the cell membrane. Inset, Acanthocytes 棘红细胞 with their typical ring-formed cell bodies with one or more blebs水泡 of different sizes and shapes.

Examination of the urine sediment by a phase constrast microscope

Dysmorphic glomerular erythrocytes>8000/ml,Acanthocytes>5%

Classification of Glomerular Classification of Glomerular DiseaseDisease

EtiologyEtiology

PathologyPathology

ClinicalFeaturesClinical

Features

Clinical syndromes and Clinical syndromes and presentationpresentation

Clinical syndromes and Clinical syndromes and presentationpresentation

Latent GN

(asymptomatic urinary

abnormalities)

Nephrotic

syndrome

Acute GN RPGN Chronic GN

microscopic or

Macroscopic hematuria

Proteinuria

Dysmorphic

Glomerular

erythrocytes

Proteinuria>3.5g/d

Hypoalbuminemia

Hyperlipidemia

Edema

Proteinuria>3.5g/d

Hypoalbuminemia

Hyperlipidemia

Edema

Hematuria

Proteinuria

(1-3g/d)

ARF

Edema

Hypertension

Red cell casts

•Rapidly deterioration of renal function

•Hematuria, Proteinuria

• oliguria or anuria

Red cell casts

•With or without systemic symptom

•Hematuria, Proteinuria

•Hypertension

•Reduced GFR

How are glomurular diseases diagnosed ?

Usually by history, physical findings,

Urinalysis and other laboratory data.

Occasionally a renal biopsy must be

performed !

Renal Biopsy ProcessingRenal Biopsy Processing

• performed by nephrologists using real-time ultrasound guidance and disposable automated biopsy needles.

• 16-gauge needles

• lower pole of the kidney


• Ultrasound scan demonstrating the deepness of needle entering the lower pole of the left kidney (centimeter)


• Needle is guided into the probe pore

• passed under ultrasonic guidance to kidney capsule.


• The trigger mechanism is released with the pt stopping the breath

•firing the needle into the kidney

• Needle is immediately withdrawn

renal biopsy material

PathologyPathology

PAS MASSON H&E PASM

Pathological classification of GN

minimal change glomerulonephritis 轻微病变性肾小球肾炎

focal segmental lesions 局灶节段性病变 diffuse glomerulonephritis 弥漫性肾小球肾炎

membranous nephropathy 膜性肾病 proliferative glomerulonephritis 增生性肾炎

sclerosing glomerulonephritis 硬化性肾炎 unclassified glomerulonephritis 未分类性肾小球肾炎

proliferative glomerulone-phritis 增生性肾炎 mesangial proliferative GN 系膜增生性肾小球肾

炎 endocapillary proliferative GN 毛细血管内增生性

肾小球肾炎 mesangial capillary GN 系膜毛细血管内增生性肾

小球肾炎 crecentic GN 新月体肾炎 Dense deposit glomerulonephritis

Pathological classification of GN

Clinical syndromes of Clinical syndromes of glomerular diseasesglomerular diseases

Asymptomatic hematuria/ or proteinuria

Nephrotic syndrome Acute glomerular nephritis Rapidly progressive glomerular

nephritis Chronic glomerular nephritis

Dysmorphic glomerular erythrocytes

Asymptomatic hematuria/ or Asymptomatic hematuria/ or proteinuriaproteinuria

Latent nephritis

• Mild chronic GN or recovery phase of

acute GN

• Isolated microscopic hematuria

(Dysmorphic RBC)

• Isolated proteinuria

• No HBP, edema or Azotemia

• Treatment is similar to chronic GN

CASE ICASE I CASE ICASE I

11 year-old male History: Intermittent hematuria x 1 year

Hx of recurrent pharyngitis Physical: tonsillitis

Urinalysis: 15 RBC/HPF

1 protein RBC casts

Lab Data: dysmorphic RBC

red blood cells per high-power field

H&EH&E

Light microscopy: diffuse mesangial hypercellularity

PASPAS

mesangial hypercellularity

IgAIgA

Immunofluorescence microscopy: diffuse mesangial IgA

Electron microscopy: mesangial electron-dense deposits.

ThePatient Has

IgA nephropathy!

IgA Nephropathy

• Most common GN• Mesangioproliferative or

other pathological types• Predominent mesangial IgA

deposit• Persistent or episode of

hematuria• Exacerbate on infection• 1/3 have elevated serum

IgA



Nephrotic syndrome Acute glomerular nephritis Rapidly progressive glomerular


Nephrotic SyndromeNephrotic Syndrome

Insidious onset Manifestations

Proteinuria > 3.5g/d Hypoalbuminemia alb < 30 g/l Edema Hyperlipidemia

Nephrotic syndrom-Nephrotic syndrom-etiology(1)etiology(1)

Primary Nephrotic syndrom

minimal change disease FSGS(focal segemental glomerular

disease) membranous nephropathy membranoproliferative GN IgAN

Nephrotic syndrom-Nephrotic syndrom-etiology(2)etiology(2)

Secondary Nephrotic syndrom Autoimmunity:SLE,

Infection: Hepatitis B or C,HIV Tumor: solid carcinoma, lymphoma Metabolic: DM, Amyloidosis Drugs: NSAIDS

Nephrotic syndrom-Nephrotic syndrom-epidemiologyepidemiology

Children Yong people Old people

Primary MCD FSGS,MsGN MN MPGNSecondary HSP SLE DN Hepatitis B HSP Tumor Inherited NS Hepatitis B MM , AL Henoch-Schönlein Nephritis Multiple myeloma , Amylosis

14 year-old, male, high-school student History: No significant medical history

Fatigue x 3 weeks Edema x 1 week

Physical: Mild generalized edema Urinalysis: 4 protein

Many hyaline casts

Few granular casts

No RBCs or RBC casts Lab Data: proteinuria 4g/d , alb 20g/l,normal renal

function, Hepatitis (-), Auto-immunity Ab (-) Renal biopsy

CASE CASE IIII

Electron Microscopy: effacement and fusion of foot processes

The patient hasMinimal change

disease!

Introduction

Incidence:

Etiology:

Clinical Features:

ClinicalCourse:

Loss of net negative charge on capillary basement membrane.

Nephrotic syndrome. Prominent proteinuria & edemaNo hypertension

Sensitive to steroid, relapse may occur.

80% of nephrotic syndrome in children

Minimal Change DiseaseMinimal Change Disease

CASE IIICASE III

65 year-old, male, Smoke for 40 years History: Fatigue x 3 months

Cough and chest pain x 2 months Facial edema x 1 week Physical: edema, Urinalysis: protein ++++ Lab Data: proteinuria 8g/d , alb 24g/l, normal renal function,

Hepatitis (-), Auto-immunity Ab (-)

Why is a thorough Clinical evaluation

important in patients with the nephrotic

syndrome !

Many such patients have

an occultmalignancy !

CASE IIICASE III

Lung Carcinoma

SilverSilver

PASPAS

CASE IIICASE III

LM-PASM:”spikes” along the GBM

CASE IIICASE III

IF: IgG deposition along GBM

CASE IIICASE III

EM: subepithelial electron dense material

It’s Clearly a case Of carcinoma related

Membranous nephropathy !

CASE II-MNCASE II-MN

Commonly occurred in middle&old-aged peopleEtiology ： Primary Secondary ： Tumor-related,

Hepatitis B related , Drugs - related Presentation: HT & Renal failure, Thrombosis

Introduction

Membranous Nephropathy

Incidence:

Etiology:

Path:

ClinicalCourse:

Immune complex disease. May associated with carcinomas, infections, drugs, and heavy metals.

Some adults develop ESRD.

Diffuse, uniform basement membrane thickening with subepithelial projections (“spikes”).

Commonly occurred in middle&old-aged people

How to treat the Nephrotic

Syndrome?

Pathogenesis/Complication

Liver

Edema

Hypoalbuminemia

Glom inflammation

Proteinuria ↑

Permeability↑

Lipoprotein Synthesis↑

Blood Lipid↑

Primary Secondary Causes

Blood volume↓

Thrombosis

CV disease↑

ARF

Infection

vitD deficiency

Protein malnutrition

Development↓

Treatment of NS

Liver

Edema

Hypoalbuminemia

Glom inflammation

Proteinuria ↑

Permeability↑


Blood Lipid↑


Causative TherapySteroid/CTX/CsAACEI/ARB

Diuretics

Liver

Edema

Hypoalbuminemia

Glom inflammation

Proteinuria ↑

Permeability↑


Blood Lipid↑


Treatment of Complication

Blood volume↓

Thrombosis

CV disease↑

ARF

Infection

Antithrombotic

Anti-infection

Diuretics/Dialysis

Statins

0.25mg/kg.d

Slow the speed of tapering

1mg/kg.d×8w

0.5mg/kg.d

Taper 5mg per 1-2week

How to use glucosteroids(1)

Maintenance for 1 year

0.25mg/kg.d


1mg/kg.d×8w

0.5mg/kg.d

Taper 5mg per week



Sufficient initial dose

0.25mg/kg.d


1mg/kg.d×8w

0.5mg/kg.d

Taper 5mg per week




Slow tapering

0.25mg/kg.d


1mg/kg.d×8w

0.5mg/kg.d

Taper 5mg per week

How to use glucosteroids



Slow tapering

Long maintenance



Nephrotic syndromeAcute glomerular nephritisRapidly progressive glomerular


急性肾小球肾炎急性肾小球肾炎 Acute GNAcute GN

History of streptococcus infection 2 weeks ago

Acute onset Prominent hematuria and RBC castsARF & HTLow C3 ， for 8weeksESR increased ， Anti-DNAseB（＋）

急性肾小球肾炎急性肾小球肾炎 Acute GNAcute GN

Endocapillary proliferation:A diffuse proliferative and exudative glomerulonephritis :infiltration of the glomerular tuft

by neutrophils and monocyte

cute GNcute GN

Treatment ： eliminating the streptococcal infection with antibiotics; supportive therapy

Prognosis: Spontaneous resolution(for children within 6-8 wks). Excellent prognosis, and rarely causes ESRD.

Rapid progressive GN

• Similar to acute GN on onset• Rapid deterioration of renal

function• Cr↑ , Oliguria and obvious

macroscopic hematuria• Crescent formation>50%• Need aggressive

therapy(Large dose of steroid

pulse therapy ＋ CTX ；Plasmaphoresis)

• Prognosis: poor, most require

dialysis.


Crescent

Idiopathic crescentic GN(RPGN) ： Type I : with linear deposits of Ig anti －

GBM antibody＋ Type II: with granular deposits of Ig

immune complex-mediated Type III: with few or no immune deposits

of Ig Pauci-immne ,ANCA＋ Type IV: anti － GBM antibody ＋ &

ANCA＋ Type V: Pauci-immne ， ANCA－


Chronic glomerulonephritis

• Clinical presentations:

Proteinuria(<3.5g/d);Hematuria;

Hypertension;Edema;Azotema(BUN/Cr↑)

• Pathological manifestations of all of major glomerulopathies.

• Exclusion of secondary cause :SLE etc.

• To correct the reversible factors: hypertension, infection, drug toxicity

Treatment of Chronic GN

• Reduce proteinuria• Control hypertension

• ACE-I or AT II receptor blocker/ antagonist (ARB): reducing proteinuria in addition to lowing of blood pressure

• Low protein diet for azotemia• Avoid nephrotoxic agents• Anti-platelet aggregation

TAKE HOME MESSAGE TAKE HOME MESSAGE ！！

One important clinic syndrome of glomerular disease: Nephrotic syndrome !

Diagnosis is based on thorough clinic evaluation !

Renal biopsy is critical for diagnosis !

THANKS THANKS ！！

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24 glomerular disease

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