Sindroma Nefrotik - Dr.chandra

8/9/2019 Sindroma Nefrotik - Dr.chandra

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Sindroma Nefrotik Sindroma Nefrotik

Kuliah Semester VII – FKUA

Ilmu Penyakit Dalam - Nefrologi

Divisi Nefrologi & Hipertensi – Lab-SMF Penyakit Dalam

FK Unair – SU Dr! Soetomo" S#rabaya


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AsymptomaticProteinuria 150 mg to 3 g per day

Hematuria > 2 red blood cells per high-power field (>1010! cells"#$

in spun urine (red blood cells usually dysmorphic$

Macroscopic hematuria%rown " red painless hematuria (no clots$& typically

coincides with intercurrent infection

'symptomatic hematuria proteinuria between attac)s

Nephrotic SyndromeProteinuria * adult >3+5g"day& child

>,0mg"hour per m2

Hipoalbuminemia 3+5g"d#

.dema

Hipercholesterolemia

#ipiduria

Nephritic syndrome/liguria

Hematuria* red cell casts

Proteinuria * usually 3g"day

.dema

Hypertension

'brupt onset usually self-limiting

Rapidly progressive glomerulonephritisenal failure oer days " wee)s

Proteinuria * usually 3g"day

Hematuria * red cell casts

%lood pressure often normal

ay hae other features of asculitis

Chronic GlomerulonephritisHypertension

enal 4nsufficiency

Proteinuria > 3g"day

hrun)en smooth )idneys

Clinical Presentations of Glomerular Disease

Feehally J, Johnson RJ,;2000


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O’Callaghan C, Brenner BM; 2000


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Droste C, von Planta M; 1992


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%asement membrane

.pithelial 6ell 7oot Process

.ndothelial 6ell

esangial 6ell

esangial atri

Schematic Representation of a Normal Glomerular Loe

Cotran RS, K!ar ", Ro##$ns S%; 199&


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Nephrotic SyndromeDefinition

' clinical entity of multiple causes

characteri8ed by *

Proteinuria > 3+5 gram " day

Edema

Hypoalbuminemia ( 3+0 g"dl$ Hypercholesterolemia

+ #ipiduria (oal fat bodies$


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Nephrotic SyndromeCauses

Primary causes

Minimal change

disease

Membranous

nephropathy

Focal segmentalglomerulosclerosis

Proliferative

4g' 9ephropathy

#. Post infectie

(H%: H6: H4:

typhoid malaria

etc$

Secondary causes

Diabetes Mellitus

Systemic / vascular diseases (immune

complex diseases$ * SLE , Periarteritis Nodosa , Amyloidosis

Drugs * NSAIDs, α -interferon, pencillamine, gold(membranous nephropathy, phenytoin ! dilantin,

lithium (chronic interstitial nephritis

Allergy * pollen, house dust, insect! sna"e bites,immuni#ation, tetanus, smallpo$

Malignancy * %odg"in&s disease, mycosisfungoides, 'L (membranous )N

enal !ein "hrombosis

Pregnancy


8/53Minimal Change DiseaseCotran RS, K!ar ", Ro##$ns S%; 199&


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SKEMA!"ME#U!US

#o$$ins an% &otran Pathologi' (asis of Dise,.


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!"ME#U!US

ww.marvistavet.com


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GLOMERULUS

Electron micrograph

"/for% 0e/t$ook of &lini'al Ne1hrology) 3rd


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Normal Po%o'yte Stru'ture+ Scanning electron microscope SEM! micrograph o" aglomer#lar podoc$te as seen "rom the #rinar$ space. %he large cell &od$ sends o#tthic' primar$ processes that "#ther rami"$ into (ne secondar$ "oot! processes thatinterdigitate with "oot processes "rom ad)acent podoc$tes. Under the "oot processes

is the glomer#lar &asement mem&rane that s#rro#nds the glomer#lar capillar$ notvisi&le in this view!.

+ormal ,odoc$te Str#ct#re


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!N"AC" P#D#C$"%S


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%&&AC%D P#D#C$"%S


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Differentiation 'et(een Nephrotic

and Nephritic Syndrome

"ypical

features #ephrotic #ephritic

/nset 4nsidious 'brupt

.dema

%lood pressure 9ormal aised

;ugular enouspressure

9ormal " low aised

Proteinuria

Hematuria

ay" may not

occur

ed-cell casts 'bsent Present

erum albumin #ow9ormal" slightly

reduced

Feehally J, Johnson RJ,;2000


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Common Glomerular Disease Presenting as Nephrotic Syndrome in Adults

Disease Asso'iation Serologi' tests

inimal change disease 'llergy atopy 9'4


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Age)Associated Prevalence of Nephrotic Syndrome *P+A,

AD$%"&H'%DE

#

10@

1!

1!

A@

1AB

11@

22

5A

10 20 30 50 !0 B0,0 @00

10

20

30

50

!0

B0

,0

@0

100

A0

M'#'MA%

&HA#(ES

FS(S

MEM)A#*$S

M&(#

*"HE

P*%'FEA"'!E

D'A)E"ES

AM+%*'D%$P$S

*"HE

A%%

AD$%"SA(E A" *#SE" *F #S

5

,251B

B!

A%%

&H'%DE#

% %%

Cohen '(, )lasso*+ RJ; 1999


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Nephrotic Syndrome

Diagnosis - Prognosis

Primary GN

Adults &hildren, of

&ure/ESD

-., .,

M&D 15C @0C 100"0

FS(S 20C 15C ,0-!0"50

M(# 30C 50"25

'gA# 10C 33"50

Cattran DC, 1999


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Nephrotic Syndrome

Diagnosis - Prognosis(cont.)

Primary GN

(cont.)

Adults &hildren , of&ure/ESD

MP(# 3-5C 1C 33"20

&rescentic 1-2C 1C 33",0

Secondary GN 0., ., B0"30

Cattran DC, 1999


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PR#"%!N.R!A


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PR#"%!N.R!A

•ar)er of 4ncreased 6ardioascular is)

•is) factor for progressie renal disease *


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#*M* 1 M'&* 2 MA&*A%)$M'#$'A

"otal $rinary Protein

3 .44 mg/day

'A Micral test Albustix5positive

mg/day

mc6g/min

74 84 844

- 04 044

.$ll$a!s ), P$*+/ JC;1999

Nephrotic

Syndrome

Micro

Albuminuria

Normal

Range

Macro

Albuminuria


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Normo- Mi'ro- Ma'ro-23

Al$uminuria

Al$uminuria

Al$uminuria

Al$uminE/'retion

#ate

mg4%ay - 30 30300 / 300

g4minute - 20 20200 / 200

Al$umin

0otal UrineProtein

1 221 501

Al$usti/#ea'tion

+eg +eg ,os

Mi'ral 0est +eg ,os ,os

D$ 6linical 'lbuminuria


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.$ll$a!s ), P$*+/ JC;1999


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Proteinuria in Adults

Presentation y Severity of Proteinuria

9 864 g/day

asymptomatic

: 86. g/daysymptomatic

swelling of feet " face

shortness of breath(in aged heart " lier disease$

gross hematuria features of hypertension

Cattran DC, 1999


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/#0 PR#"%!N.R!A MA$ CA.S% R%NAL !N1.R$/#0 PR#"%!N.R!A MA$ CA.S% R%NAL !N1.R$

Pro$imal %ellPro$imal %ell %ell n'#ry%ell n'#ry Progressive enal DamageProgressive enal Damage

Protein

Mole(#les

Protein

Mole(#les FibroblastsFibroblasts Ma(rop)agesMa(rop)ages

%ytokines

L-*

PD+F-,NF." ot)ers

%ytokines

L-*

PD+F-,NF." ot)ers

Matri$ ProteinsMatri$ Proteins %ollagen%ollagen

%)emokines/

M%P-

0-

%)emokines/

M%P-

0-

oto RD; 199- oto RD; 199-

Fibrosis

nflammation

Patients ;ith P*"E'#$'A


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Patients ;ith P*"E'#$'A

2,-hr urine protein 150 mg"day2,-hr urine protein > 150 mg"day

P'H/#/?46

Erine protein electrophoresis 2,-hr collection

Probably normal

History Physical

.aminationErine dipstic) test

: 86. g/day < #ephrotic Syndrome 3+5 g"day 'bnormal proteins

.clude *

CHF

Hypertension

Nephritis

FeverATN

.clude *

Causes of Nephrotic

Syndrome

6onsider * Transient proteinuria Benign persistent proteinuria Orthostatic proteinuria

6onsider *

Amyloidosisor

Light-chain isease

.clude *

!ultiple

!yeloma?lucose

4ntolerance9o ?lucose

4ntolerance

6onsider *


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%valuation of !solated Asymptomatic Proteinuria

ecumbent oernight

4f ?7 or %P abnormal if

proteinuria increases

'symptomatic proteinuria

Iuantitatie protein ecretioneasure glomerular filtration rate (?7$


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Patients ;ith

P*"E'#$'AHistory Physical

.amination Erine dipstic) test

: 7.4 mg/day 150 mg"day

PA"H*%*('&Probably normal

$rine protein electrophoresis

0>5hr collection

0>5hr urine protein

'l(a$ary ', van .y*+ DB; 199


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> 3+5 g"day 3+5 g"day 'bnormal proteins

#ephrotic

Syndrome

$rine protein electrophoresis

0>5hr collection

Exclude <

CHF

Hypertension

NephritisFever

ATN

Exclude <

Causes of

nd Nephrotic

Syndrome

&onsider Transient proteinuria Benign persistent

proteinuria Orthostatic proteinuria

&onsider

Amyloidosis

Or

Light-chain isease

Exclude <

!ultiple

!yeloma

'l(a$ary ', van .y*+ DB; 199


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:86. g/day

#ephrotic Syndrome

(lucose 'ntolerance #o (lucose

'ntolerance

&onsider <


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E?AM'#A"'*# SE*%*(+

Elevated

A#A

%o;

&81 &>

Positive

A#&A

Positive

anti5(M)

antibody

Serologic

examination

#E(A"'F

Hepatitis )

or

H'!

antigenemia

&onsider

L#p#s +N

&onsider

L#p#s +N#ost $nfectious "N

Cryoglo%ulinemia

or

!em%rano

proliferative "N

&onsider

Systemicvasculitis

or

&egener's

granulomatosis

&onsider

"oodpature'sSyndrome

&onsider

Focal sclerosis!inimal change

disease

rugs

&onsider

Hepatitisor

A$S related

nephropathy

E#A% )'*PS+

0/ UND0L1N+ DS0/S0

P020N S0%3ND/1 P3+0SS3N 'l(a$ary ', van .y*+ DB; 199


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N%P/R#"!C S$NDR#M%

&ormation of Nephrotic %dema


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Underfill Overfill

Proteinuria

Hypoalbuminemia

Plasma colloid

oncotic pressure

Plasma olume

:asopressin

'trial 9atriureticPeptide ('9P$

normal"low

enin-angiotensin

system actiated

'ldosterone

Jater

retentionEdema

odium

retention

Primary tubular

defect causing

odium retention

Plasma olume

normal"

:asopressin

normal '9P

'ldosterone

Starling forces

D* +he "idney is relatiely resistant

to ANP in this setting, so it has

little effect in countering retention

&ormation of Nephrotic %dema

Feehally J, Johnson RJ;2000


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Coagulation Anormalities in Nephrotic Syndrome

Erine

6learance

&oagulation proteins *

7ibrinogen factors : :44 on

Jillebrand factor protein 6α1-macroglobulin

Enchanged " reduced *

Prothrombin factors 4G G G4

G44 antithrombin 444

Platelet aggregability

:olume contraction

Hemoconcentration

4mmobility

Hepatic

synthesis

Hyperlipidemia

'cceleratedatherogenesis

:enous thromboembolism 'rterial thrombosisFeehally J, Johnson RJ; 2000


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Lipid Anormalities in Nephrotic Syndrome

#ecithin cholesterol

acyltransferase (#6'$

actiity

Hepatic

synthesis

Hepatic secretionH


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!ndications for Renal 'iopsy in Adults

a Diagnosis K what is it L

b Prognosis K what is going to happen L

c "herapy K what is the treatment L

Cattran DC, 1999


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Nephrotic Syndrome"reatment

(eneral


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Frusemide

can be used aloneincrease the dose till diuresis occurs

F supplement often reMuired

Spironoloactonehould be aoided if serum F is high " patients with

renal impairement

&hlorthia@ide

synergistic action with frusemide and spironolactone

'ombination of agents aboe

Diuretic "reatment

hye .K; 1999

Management of %dema in Nephrotic Syndrome


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Management of %dema in Nephrotic Syndrome

/ral loop diuretic e+g+ Furosemide ,0 mg bid

)umetanide 1 mg bid


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Correction of Aluminemia4nfusion of 9a free albumin → induces diuresis

benefit L

"reatment of !nfectionsEse appropriate antibioticsDipyridamole and 0arfarin Plus Regimen

P and W + regimen /&oo 0eng Thye1

Dipyridamole

anti-platelet N anti-P


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"reatment

of /ypertension

Reducing

Proteinuria

'ngiotensin 6onerting .n8yme 4nhibitor

CA&E ' 'ngiotensin 44 eceptor 'ntagonist

CA)6alcium 6hannel %loc)er K 9on


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• #ower blood pressure

• #ower glomerular capillary pressure

• 4mproe glomerular permeability to plasma proteins

(protein$

• 4nhibit hypertrophy in glomerular and tubular cells

AC% !nhiitors 2Renal Protective %ffects

oto RD; 199-


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R%D.C!NG PR#"%!N.R!A 0!"/ AC% !N/!'!"#RS

MA$ SL#0 PR#GR%SS!#N #& R%NAL D!S%AS%

• educe mesangial inOury and proliferation

• educe ris) of tubulointerstitial damage

• 4mproe hyperlipidemia K reduce glomerular

and tubular inOury


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AC% !nhiition and Glomerular &unction

EA

Filtered

Proteins

)o;mans

&apsule

(lomerulusAfferent

Arteriole

)P

(&P

Efferent

Arteriole

%e;is E6 6ontrib 9ephrol 1AA!&77*20!-213+


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Steroid

/i t l i P tt d St id R i i


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/istologic Patterns and Steroid Responsiveness in

Diseases Causing Nephrotic Syndrome

Mesangial

hypercellularity

Focal segmental

glomerulosclerosis

CFS(S

Minimal change

disease CM&D

'gM Dense

Deposit

disease

Steroid

responsive

Mason PD; 2000


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Cytoto3ic Agents 2

6yclophosphamide

6hlorambucil

6yclosporine

ycophenolate mofetyl

others


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Summary

' clinical entity of multiple causes

characteri8ed by *

Proteinuria > 3+5 gram " day

EdemaHypoalbuminemia ( 3+0 g"dl$

Hypercholesterolemia

+ #ipiduria (oal fat bodies$

&auses


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Summary (cont.)

"reatment of #ephrotic Syndrome

(eneral


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0E#IMA KASI50E#IMA KASI5

Divisi Nefrologi & Hipertensi – Lab-SMF Penyakit Dalam

FK Unair - SU Dr! Soetomo

Kuliah Semester VII – FKUA ,64,7

Ilmu Penyakit Dalam – Nefrologi


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Sindroma Nefrotik - Dr.chandra

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