Dwi Lestari PartiningrumNephrology and Hypertension Division,

Internal Medicine DepartmentMedical Faculty Diponegoro University/ Kariadi HospitalMedical Faculty Diponegoro University/ Kariadi Hospital

IntroductionIntroduction Glomerulonephritis (GN)o Initially coined by Klebs.oA group of diseases occuring either as primaryoA group of diseases occuring either as primary

renal disorders or a secondary manifestation of a sistemic disease statesistemic disease state.

o Inflammation within the glomerulus.oRenal manifestation of hematuria, proteinuria

and impaired glomerular filtrationp goUnpredicteble disease course make clinical

management problematicmanagement problematic

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DEFINITION

Glomerulonephritis: (GN) injury withGlomerulonephritis: (GN) injury with evidence of inflammation such as l k t i filt ti tib d d itileukocyte infiltration, antibody deposition, and complement activation.

GN primary: pathology is confined to the kidney.p y p gy y GN secondary: when part of a multisystem disorder.

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EM : Normal glomerular capilaryEM:Normalglomerularcapilary

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NOMENCLATURE

Acute: glomerular injury occurring over days orAcute: glomerular injury occurring over days or weeks.

Sub acute or rapidly progressive (RPGN): over eeks or a fe monthsweeks or a few months.

Chronic: over many months or years.

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I j L li tiInjuryLocalization

1. Overview of slides : assesses injury and localizes to the specific anatomic compartmentlocalizes to the specific anatomic compartment(glomerular/ vascular/ tubulointerstitial).

2. Assessment of type of injury, extent of injury in h l leach glomerulus.

Terminology : diffuse, focal, global and segmental.

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Diffuse : at least 60% glomeruli involved.

Focal : some glomeruli < 60%.

Global : involved 1 glomerulus as a whole.

Segmental : part of 1 glomerulusSegmental : part of 1 glomerulus.

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P lif ti l l ll b Proliferative : glomerular cell number (intracapillary and extracapillary)

A crescent: is a half-moon shaped. Cells in Bowman`s space.

Membranous : expansion of the GBM by immune deposits.p

Sclerosis : non-fibrilar extracellular material Fibrosis : Collagens type I and III Fibrosis : Collagens type I and III

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Mechanism of Injury in Glomerulonephritis

Immuno pathogenesis

j y p

Immuno pathogenesis

G ti InflammationGeneticInfluence Genetic

Influence

Resolution ScarringResolution Scarring

Variable rateVariable rateof progression

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Immunologic Mechanism of Glomerular Injury

In situ antigen-antibody interaction (1) Exogenous planted antigens (1)

Circulating immune complexes (2)Circulating immune complexes (2) Intrinsic glomerular antigen (3)Cell mediated mechanism (?) Cell-mediated mechanism (?)

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Activation of mediators of

l lglomerular injury

Activation of di t fmediators of

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Mechanism of Immune Renal InjuryEtiologic Agent Infections

Loss of tolerance

Immune Response

IR Genes

Deposit Formation

AntibodyIgG, IgA T Cells

Deposit Formation

Mediation

In situ, complex trapping

Mediation

Eff t C ll

Complement, Chemokines Cytokines, Vasoactive

Effector CellsPMNs, macrophages Glomerular cells (mesangial prolif)

ResponseProliferation, PDGF Sclerosis, TGF - Dwi-Lestari

Complement activation

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Glomerulonephritis Classification

Clinical Presentation (5 Clinical manifestation). Histopathological Classification: (percutaneus Histopathological Classification: (percutaneus

biopsy and open biopsy).Eti l d P th i Cl ifi ti Etiology and Pathogenesis Classification.

Immunological Classification.

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Clinical Presentations of glomerular diseaseAsymptomatic

Proteinuria 150mgto3g/dayHematuria > 2 red blood cellsHematuria >2redbloodcells

Perhighpowerfield(>10x106 cells/LInspunurine(redbloodcells

Usuallydysmorphic

NephriticsyndromeOliguriai d ll

Nephrotic syndromeProteinuria;adult>3,5g/day

Hematuria :redcellscastsProteinuria;usually40mg/hperm2

EdemaHypercholesterolemia

Lipidemia

Chronic glomerulonephritis

OedemaAbruptonset

Lipidemia

RapidlyprogressiveglomerulonephritisRenal failure over days/weeksChronic glomerulonephritis

HypertensionRenalinsufficiensy

Proteinuria >3g/day

Renalfailureoverdays/weeksProteinuria usually

Definition of Clinical Syndrome

AcuteNephritic Nephrotic RPGNSyndrome Syndrome

Acute onset of : Insidious onset of : RPGN Hematuria Hypertension Oliguria

Proteinuria (severe) Edema (severe/ anasarca)

Hematuria w/ RBC cast Oliguria (variable) Oliguria

Edema (moderate) Proteinuria (mild-

) Hypoalbuminemia Hypercholesterolemia

Lipid ia

g ( ) Proteinuria (variable) Hypertension (unusual)moderate)

Azotemia

Lipiduria Hypercoagulability

(unusual)

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Moderatehypertension

Mildhypertension

BPnormalBPnormalBloodpressure

HAEMATURIAmild

PROTEINURIAmild

PROTEINURIA3 5g +

PROTEINURIA3 5g +

Urinedipstick mildmild

Moderaterenal

Mildrenal

3.5g+3.5g+

GFR normalGFR normal

dipstick

GFR renalimpairment

impairmentGFRnormalGFRnormalGFR

Nephrotic syndrome Nephritic syndrome

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Nephrotic and Nephritic PresentationNephroticandNephriticPresentation

Nephrotic Nephritic

Minimal change ++++Minimal changeMembranous nephropathy

++++++++

-+

Diabetic glomerulosclerosisAmyloidosis

++++++++

++y

FSGSMPGN

+++++

+++++MPGN

Acute post streptococcal GN+++

+++++++

Cresentic glomerulonephritis + ++++Dwi-Lestari

Gl l DiGlomerular Diseases

Nephritic Nephrotic Syndrome

Primary renal Post Infectious Minimal changeIg A nephropathy Focal SclerosisRPGN Membranous

nephropathyMembrano proliferative

Systemic Disease Vasculitis Diabetes MellitusWegeners Amyloid

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Nephrotic Syndrome

Clinical features of nephrotic syndromeProteinuria (>3.5g/24h)

HypoalbuminaemiaOedema

+/- Hypercholesterolaemia

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Nephrotic Syndrome PathophysiologyDiagnostic triadDiagnostic triadProteinuria > 3.5g/dLSerum Albumin < 30g/LOedema

Disease of glomerular capillary wallUrinary protein lossLow plasma oncotic pressureOedema Low plasma oncotic pressureSalt and water retention by kidneys

ComplicationsH h l t l i I d h ti th i d d dHypercholesterolemia Increased hepatic synthesis and reduced

metabolism of lipoproteinsThrombosis Venous obstruction caused by oedema

Increased hepatic synthesis of clotting factorsurinary loss of anti thrombotic protein (prot C,prot S, ATIII)

Infections Urinary loss of immunoglobulins and other defence protein

Renal Failure Intravascular volume depletion (acute)Renal Failure Intravascular volume depletion (acute)Intrarenal oedema (acute)Primary renal disease causing glomerular damageProteinuria causing interstitial inflamationProteinuria causing interstitial inflamation

Malnutrition Severe protein loss

Underfill OverfillFormation of nephrotic edema

Underfill

Proteinuria

Overfill

TubularDefect causing

Sodium retentionHypoalbuminemia

Sodium retention

Plasma colloidOncotic pressure Normal/raised

Plasma volume

Reducedplasma volume

Vasopresin Atrial natriureticPeptide (ANP)Normal/low

Renin angiotensinSystem activated

Aldosteron Vasopressin

normalANP Aldosteron

Waterretention

Sodiumretentionretention

Edema

retention

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Lipid abnormalities VLDL deposition inVLDL deposition inin nephrotic syndrome

VLDLVLDL

Catabolism

VLDL deposition in vascular tissues VLDL deposition in vascular tissues

IDLIDLHepatic synthesis

Catabolism Endhotelial

lipoprotein lipase

O idi dLDLLDL

OxidizedLDL

Ath i itAth i itHepatic

secretionHDLHDL AtherogenicityAtherogenicity

Urine clearance

secretion HDL

HDL3HDL3Urine clearance of smaller HDL3

Cholesterol removal from tissue to liver

Lecithin cholesterol

acyltransferase

Lipoprotein( )

Lipoprotein( )

HDL2HDL2from tissue to liver

impaired

AtherogenicityAtherogenicity

y(LCAT) activity

(a)(a) AtherogenicityAtherogenicity

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Coagulation abnormalities in Nephrotic Syndrome

Coagulation proteins

Raised: fibrinogen, Hepatic

synthesis

g ,factors V, VII, von Willebrand factor, protein C 1 -

l b liUrine

Unchanged/reduced:Prothrombin factors

IX X XI XII

macroglobulin clearance Hyperlipidemia

Accelerated IX, X, XI, XII, antithrombin III

Platelets aggregability

Accelerated atherogenesis

Platelets aggregability

Volume concentrationHemoconcentration

Immobility

A t i l th b i VenousArterial thrombosis Venous thromboembolism

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asymptomatic proteinuriaasymptomatic proteinuriay p py p p

Quantitate protein excretionQuantitate protein excretionMeasure glomerular filtration

rate (GFR)Measure glomerular filtration

rate (GFR)Normal GFR

Non-nephrotic proteinuria

Normal GFRNon-nephrotic

proteinuria

Reduced GFR

Reduced GFR

Dipstick negative

Orthostatic proteinuria

Dipstick negative

Orthostatic proteinuria

Recumbentovernight

SerologictestsUltrasoundIfGFRorbloodproteinuria

No further action

proteinuriaNo further

actionPersistent

fixed proteinuria

Persistent fixed

proteinuriaConsider

renal biopsyConsider

renal biopsy

pressure(BP)abnormal,ifproteinuriaincreasesproteinuriaproteinuria

Reassess at 6-12 th

Reassess at 6-12 th

renal biopsyrenal biopsyincreases

Evaluation of isolated

12 monthsUrine protein

GFRBlood pressure

12 monthsUrine protein

GFRBlood pressure

If normal GFR and BP persist:

reassess

If normal GFR and BP persist:

reassess Evaluation of isolated asymptomatic proteinuria

pp reassess annuallyreassess annually

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Glomerular Disease that causedGlomerular Disease that caused Nephrotic Syndrome

Mi i l h h ti d (MCNS) Minimal change nephrotic syndrome (MCNS) Focal segmental glomerulosclerosis (FSGS) Membranous nephropathy (MN) Membrano proliferative glomerulonephritis Membrano proliferative glomerulonephritis

(MPGN) Dense deposit disease Dense deposit disease Immunotactoid glomerulopathies (Amyloidosis)

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LM EM IF

Histopathological Manifestation

LM EM IF

MCNS ( ) Foot proceses fusion ( )MCNSMN

Focal Sclerosing

(-)Thick GCW without glmhypercellularity

Foot proceses fusion

Subepithelial EDD (lumps)

(-)

Finely granular,CWg

GNMPGN

P t t GN

FSGSThick GCW with glmhipercelullarityHypercellular glms

Foot proceses fusionSubendothelial EDD, mesangial interposition.S b ith li l EDD (h )

IgM (segmental)CW Ig and C

Poststrep GNIgAN

DM

Hypercellular glmsMesangial proliferation

Glomerulo Sclerosis

Subepithelial EDD (humps)Mesangial EDD

Thick GBM mesangial

CW Ig and C3Mesangial IgA

CW pseudolinearDM

Amyloidosis VariableCongo red stain (+)

Thick GBM, mesangial expansion.Amyliod fibrils

CW pseudolinear

(-)

SLE

RPGN

Various patterns

crescents

EDD- multiple sites

variable

CW and mesangial Ig, C3, C1qCW (-) or granular or linearlinear

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MINIMALCHANGENEPHROTICSYNDROME(MCNS)

Histopathology

LM : glomerular structure mainly normal IM IM : -EM : diffuse effacement of foot processes (podocytes).

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EM : Fusion foot processes

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FocalandSegmentalGlomerulosclerosis

LM : glomeruli may appear normal in early disease, later lesion show segmental areas of sclerosis and hyalinosislesion show segmental areas of sclerosis and hyalinosis of the glomerular tuft, expansion of mesangial matrix and interstitial fibrosis with tubular atrophy.interstitial fibrosis with tubular atrophy.

IF : negative, except for IgM and C3 in sclerotic lesion.EM :EM :

Idiopathic FSGS : diffuse effacement of foot processes and degeneration of podocytesand degeneration of podocytes

Secondary FSGS : patchy effacement of podocyte foot processesprocesses.

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Perihilar segmentalPerihilar segmental sclerosis

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Membranous Nephropathy (MN)

LM : GBM is thickened and the capillary wall more rigid th l i d d th ill ll i iththan normal; in advanced cases, the capillary wall is with spikes of GBM extending between and around subepithelial deposits. Advanced glomerular lesions are

i t d ith t b l t h d i t titi l fib iassociated with tubular atrophy and interstitial fibrosisIF : Granular glomerular capillary wall deposits of IgG

C3 are characteristics even if light microscopy is normalC3 are characteristics even if light microscopy is normalEM : Subepithelial electron dense deposits along the

capillary loops with effacement of overlying foot With d i di GBM t i l iprocesses. With advancing disease, new GBM material is

laid down at the sides of and around the deposits.

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Stages of Membranous Nephropathy

I. Subepithelial electron deposits in GBM, no GBM projection adjacent to deposits.

GII. The are GBM projections between deposits so called Spikes.

III. The deposits become incorporated in b t bbasement membrane.

IV. The deposits start to fade away leaving luscent gaps and a thickened basement membranebasement membrane

V. Normal subepithelial zone of GBM, which has been repaired, and the disturbance has been pushed to thedisturbance has been pushed to the subendothelial zone

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MN : PAS staining

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MN : PAM staining

spikes

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Ig G

C3

wie pmDwi-Lestari

endothelendothel

Subepithelial deposits

Foot processes fusion

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MembranoproliferativeMembranoproliferative Glomerulonephritis (MPGN)

Type I : immune complex mediated. LM, EM : Mesangial hypercellularity with subendothelial and mesangialhypercellularity with subendothelial and mesangial immune complex deposits, capillary wall mesangial interposition, and monocyte infiltration. IF : granular mesangial and capillary wall IgG C3 and IgMmesangial and capillary wall IgG, C3 and IgM.

Type II : Deposition of electron dense material within capillary wall (spindle shape/ sausage) . IF : complement p y ( p p g ) pC3.

Type III : Subepithelial and subendothelial deposits associated with GBM disruption and lamina densaassociated with GBM disruption and lamina densa layering.

All types have double-contoured GBM or Tram track/ rail road appearanceroad appearance

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IgG MPGN type Iyp

C3Dwi-Lestari

EM : tram track appearance GBMEM : tram track appearance

GBM (blue)

GBM

GBMdeposits

GBM

Mesangial hypercellularity

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MPGN type II : C3

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MPGN type II : Dense Deposit Disease

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Glomerular Disease that caused H t i / N h iti S dHematuria / Nephritic Syndrome

Post streptococcal glomerulonephritis/ Acute glomerulonephritisAcute glomerulonephritis Ig A Nephropathy

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Ig A Nephropathy

LM : global or segmental mesangialLM : global or segmental mesangial hypercellularity; mesangial deposits may be seen with trichromet t c o e

IF : mesagial IgA and C3, co-deposition of mesangial IgG or IgM frequent. Deposits may

i ll d i l h GBMoccasionally extend to involve the GBM.EM : mesangial deposits often with clustering at

the paramesangial basement membranethe paramesangial basement membrane

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Ig A

C3

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Erythrocytes in urinary space

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Post streptococal glomerulonephritis

LM : glomerular tufts are enlarged, hypercellular,LM : glomerular tufts are enlarged, hypercellular, with leucocytes in glomerular capillaries. Hypercellularity maybe global or segmental.Hypercellularity maybe global or segmental.

IF : Large, irregular subepitelial, and some mesangial and/or subendothelial depositsmesangial and/or subendothelial deposits, usually with Ig G, Ig M, and complement.EM b ith li l H h d it EM : subepithelial Hump shape deposits some mesangial and subendothelial deposits.

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S d Gl l DiSecondaryGlomerularDisease

Disease associated with Nephrotic SyndromeDisease associated with Nephrotic Syndrome Amyloid nephropathy

Di b t N h th Diabetes Nephropathy

Disease associated with nephritic nephrotic syndrome or RPGNy

Lupus nephritis Anti GBM antibody Anti GBM antibody

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AmyloidNephropathy

LM : pale acellular eosinophilic material infiltrates mesangial areas and peripheral capillary loops,

t i l ll t i d it b larterioles, small arteries, and peritubular interstitium may also be involved, Congo stained positivepositive

IM : no depositsEM d l i t d fib il f 10 t 12EM : randomly oriented fibrils of 10 to 12 nm

diameter replace the mesangium and GBM

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DiabeticNephropathy

LM : diffuse or nodular mesangial expansion with thickened GBMsthickened GBMs

IF : pseudolinear deposition of albumin and IgG along GBM non-spesific IgM and complementalong GBM, non spesific IgM and complement may be present.

EM : diffuse or nodular mesangial expansionEM : diffuse or nodular mesangial expansion, thickened GBM

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Ig GIg G

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Lupus NephritisLupusNephritisLM : WHO classificationLM : WHO classification

I : Normal LM II : Mesangial proliferative glomerulonephritis ( with immune

l li it d t i )complex limited to mesangium) III : Focal proliferative glomerulonephritis IV : Diffuse proliferative glomerulonephritisp g p V : Membranous glomerulonephritis VI : Sclerosing

IF A f ll h f i l b li d l t IF : A full house of immunoglobulins and complements.EM : dense deposits in

II : mesangial II : mesangial III and IV : mesangial, subendothelial, occasional subepithelial V : subepithelial

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IF : Full house

Ig GIg M

Ig AIg A

C3 C1qDwi-Lestari

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Fingerprints pattern

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Rapid Progressive GlomerulonephritisRapidProgressiveGlomerulonephritis(RPGN)

Synonym Goodpastures syndrome/ anti GBM

LM : glomerulonephritis without tuft hypercellularity crescents frequenthypercellularity, crescents frequent.

IF : continuous linear IgG and C3 along GBMEM : No deposits

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IgG linear staining

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GlomerulonephritisTreatment

General Management (symptomatic therapy)therapy)

Therapies for spesific glomerular diseases (therapy spesific)(therapy spesific)

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GeneralManagement(symptomatictherapy)

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S t ti ThSymtomatic Therapy

EdemaEdema

Proteinuria

Hypertension

Hyperlipidemia

Hypercoagulable stateHypercoagulable state

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Edema

Focus on sodium restriction and diuretics.Focus on sodium restriction and diuretics. Thiazides are a reasonable treatment choice for

patients with mild edema and normal renalpatients with mild edema and normal renal function.

most patients will require a loop diuretic such as furosemide for adequate sodium balance.

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P t i iProteinuriaThe cornerstone management of proteinuria

inhibition of the renin-angiotensin system (ACEIinhibition of the renin angiotensin system (ACEI or ARBs)

R d d i t l l d dReduced intraglomerular pressure reduced protein filtration.

Evidence in diabetes of ACEi and ARBs Proteinuria may also be reduced by loweringProteinuria may also be reduced by lowering

patients mean arterial pressure (MAP)

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H t iHypertension The underlying pathophysiology of hypertension in

primary glomerular disease :primary glomerular disease :oPrimary renal NaCl retention volume

iexpansiono Intrarenal activation of renin-angiotensin systemg yoActivation sympathetic nervous systemo vasoconstrictor (thromboxane, endothelin) and vasorelaxant (NO, prostaglandins)

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MDRD Study Hypertension control improves proteinuria & GFR

0

Hypertension control improves proteinuria & GFR

-3

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Protein Excretion-9

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1.0 g/d

Protein Excretion

-1280 85 90 95 100 105 110

Mean Follow Up MAP (mmgHg)Mean Follow-Up MAP (mmgHg)

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G lMaintain SBP of 120-130 mmHg and DBP of 70-80 mmHg. Do not ll di t li BP t f ll b ll 70 80 H if t tiGoals : allow diastolic BP to fall bellow 70-80 mmHg if symptomatic coronary

artery disease is presentACEi or ARB preferredACEi or ARB preferred

Use NaCl restriction and/or diuretic (thiazides, loop acting, spironolactone oreplerenone) to augment effectiveness

Agents :p p ) g

Direct renin inhibitors may also be used selectively

Adjunctive therapy with calcium channel blockers (CCB) may beAdjunctive therapy with calcium channel blockers (CCB) may be used for optimal BP controlFor mono therapy with ACEi or ARB, the maximum tolerated dosage

Dosage :

should be used, preferably to assure both daytime and night-time control of BP to desire goals. Ambulatory monitoring of 24-h BP may be neededDosage : be needed.For combination ACEi & ARB therapy the maximum recommended dosage of each agent should be used, with monitoring of serum g g gpotassium levels.

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H perlipidemiaHyperlipidemia Low in total cholesterol and saturated fat; vegetarian/ soy diet

Stop smooking

Modest exercise

Avoid excessive alcohol

HMG co reductase inhibitors (lovastatin simvastatinHMG co-reductase inhibitors (lovastatin, simvastatin, pravastatin, atorvastatin, resuvastatin, flufastatin)

Probucol (may lower HDL )Probucol (may lower HDL2)

Bile acid sequestering agent (cholestyramine, cholestipol, lli ll id)psyllium colloid)

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Hypercoagulable stateHypercoagulablestateIncreased (prothrombotic)Increased (prothrombotic)

FibrinogenPlatelets (and platelet adhesiveness)Plasma viscocity (cholesterol, lipid)Lipoproten (a)Plasminogen activator inhibitorPlasminogen activator inhibitor

Decreased (antithrombotic)

Active protein CActive protein CActive protein SAnti thrombin III

Long term anticoagulation is recommended for patients with documentedrecommended for patients with documented thrombotic episodes.

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Specific Therapies forSpecific Therapies for Glomerulonephritis

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1. Minimal change glomerulopathy.1. Minimal change glomerulopathy.

Hi h d d i (1 k i 80 ) i High-dose prednisone (1 mg per kg, maximum, 80 mg) is used as primary therapy for at least 12 weeks.

F l i d t id d d dditi For relapsing and steroid dependence cases addition of cytotoxic agents (e.g., cyclophosphamide or chlorambucil) cyclosporine A or possiblychlorambucil), cyclosporine A, or possibly mycophenolate mofetil, may be effective.

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2 Membranous nephropathy2. Membranous nephropathy.

This disease is often slowly progressive and patients may have spontaneous remissions.

Certain patients high risk for progressive renal injury.

Clinical risk factors heavy proteinuria >8 mg per day, hypertension, diminished GFR, male gender, and greater than 20% tubulointerstitial fibrosis on renal biopsy.

Low Risk Steroid effective. High risk : steroids combined with a cytotoxic agent.g y g

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3 MPGN3. MPGN

5% f l l di i d lt 5% of glomerular disease in adults, tend to carry a poor renal prognosis. 60% patients will progress to ESRD in 10 years. Unfortunatel no established therapy exists for MPGNUnfortunatel, no established therapy exists for MPGN. Secondary causes must be fully evaluated, because

diseases such as chronic bacterial infection hepatitis Cdiseases such as chronic bacterial infection, hepatitis C infection, and cryoglobulinemis, as well as leukemias and lymphomas all have therapies that may lead to remission y p p yof the renal disease.

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4 F l d t l l l l i4. Focal and segmental glomerulosclerosis

20% of idiopathic nephrotic syndrome in adults FSGS FSGS and MCD within the same spectrum of

disease but the prognosis is significantly worse in FSGSFSGS.

High-dose corticonsteroid therapy 30% of patients will achieve remission

70% fail cytotoxic agents such as cyclosporin, cyclophospamide, or chlorambucil.

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5. IgA nephropathy (Bergers disease)g p p y ( g )

the most common form of primary glomerular disease, Slowly progressive renal disease ESRD in 20% to 40%

(20 years)

a minority of patients RPGN corticosteroids (? further studies needed) patientscorticosteroids (? further studies needed) patients

with proteinuria >1 mg per day (0.5 mg per kg on alternate days).

For crescentic disease, short-term, high-dose prednisone may be of benefit.

The use of cytotoxic agents , MMF sometimes employed in patients with rapidly progressive disease.p y p p y p g

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6. Lupus nephritis

Lupus nephritis is the paradigmatic immune complex disease of the kidney with widecomplex disease of the kidney with wide spectrum diseases. th f i l di t d therapy for immune complex-mediated glomerulonephritis include high-dose

ti t id t d h l tcorticosteroids, cytoxan, and mycophenolate mofetil is effective to be of benefit.

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7 Anti GBM disease and Goodpastures7. Anti-GBM disease and Goodpasture s syndrome

PA : Crescents and immunofluorescent a linear pattern staining for IgG an anti-GBM autoantibody.

Clinically, as isolated renal dysfunction (anti-GBM disease) y, y ( )or as renal disease in conjunction with pulmonary involvement (Goodpastures syndrome)

Treatment combination of high-dose steroids, cytoxan therapy, and plasmapheresis to remove the anti-GBM antibody.

Oliguric patients poor renal prognosis.

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Clinical syndrome Manifestation Major etiologies

Asymptomatic proteinuria Urinary protein excretion < 2 g/d Low-grade glomerular disease ( I A h th MN ( IgA nephropathy, MN or MPGN)Heriditary glomerular disease (Alports syndrome)Tubulointerstitial disease

Asymptomatic hematuria Urinary RBCs > 2/ HPF (spun sediment)

Low-grade glomerular disease ( IgA nephropathy, Thin basement membran disease)basement membran disease)

Nephrotic syndrome Heavy proteinuria (>3,5 g/d), edema, high serum cholesterol, urine lipids

MCNS, FSGS, MN, MPGNDiabetic nephropathyAmyloid (myeloma LCDD)Amyloid (myeloma, LCDD)Fibrillary GN

RPGN Presents as GN with ARF (oliguria, rising serum creatinin)

Anti GBM nephritis (Goodpastures)Vasculitis Syndromes (Wegeners polyangiitis, HSP, mixed cryoglobulinemia)Immune-complex associated Immune complex associated (IgAN, poststrep GN)

Nephritic syndrome RBCs, RBC cast, proteinuria, hypertension, renal disfunction.

Poststreptococcal AGNOther post infectious GN (abcess, endocarditis)IgA nephropathyLN (WHO class III/ IV)Dwi-Lestari