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BAB I

PENDAHULUAN

Systemic lupus erythematosus (SLE) is a generalized autoimmune disorder

characterized by T and B cell hyperactivity with autoantibodies against numerous

cell components and deposition of immune complexes The disease has a

multifactorial pathogenesis with genetic! hormonal and environmental

components"!# $n autoimmune diseases! infiltration with T cells or deposition of

autoantibody%containing immune complexes in target organs! such as &idneys!

causes early inflammatory lesions The early immune mediated in'ury is believed

to trigger a series of events! including complement activation! chemo&ine

production! further inflammatory cell infiltration! and inflammatory cyto&ine

release! eventually resulting in deposition of extracellular matrix (abdel salam)

in'al merupa&an organ yang sering terlibat pada pasien dengan SLE Lebih

dari *+, pasien SLE mengalami &eterlibatan gin'al sepan'ang per'alanan

penya&itnya (re&omendasi lupus)Lupus nephritis is a common and serious complication of systemic lupus

erythematosus (SLE) and most severe in -frican%-merican female adolescents

Thirty to fifty percent of patients will have clinical manifestations of renal disease

at the time of diagnosis! and .+, of adults and /+, of children develop renal

abnormalities at some point in the course of their disease(harrison)

0ephritis in SLE causes morbidity and mortality 1ne%third of patients with

systemic lupus erythematosus (SLE) nephritis have flares despite the best

treatment and still progress to end%stage renal disease"#!" T2%3" plays a dual

role during the development and progression of immune%mediated inflammatory

diseases The enhanced T2%3" production in tissues induces local fibrogenesis

and ultimately causes fulminant organ damage (abdel salam)

Lupus nefritis memerlu&an perhatian &husus agar tida& ter'adi perburu&an

dari fungsi gin'al yang a&an bera&hir dengan transplantasi atau cuci darah Bila

tersedia fasilitas biopsi dan tida& terdapat &ontra indi&asi! ma&a seyogyanya

"

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biopsi gin'al perlu dila&u&an untu& &onfirmasi diagnosis! evaluasi a&tivitas

penya&it! &lasifi&asi &elainan histopatologi& gin'al! dan menentu&an prognosis

dan terapi yang tepat (re&omendasi lupus)

#

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# Etiologi

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$mmune complex formationdeposition in the &idney results in intra%

glomerular inflammation with recruitment of leucocytes and activation and

proliferation of resident renal cells (figure ?) (sample)

(Sample)

#:

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$L%# receptors! $L%.! interferons ($20%H and I)! T02%H and transforming

growth factor (T2%J) are upregulated resulting in chronic inflammation

and chronic oxidative damage with clinical manifestations of the disease

(:# L5enal

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*

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(re&omendasi)

(sample! #+"#)

(re&omendasi)

/

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Bila biopsi tida& dapat dila&u&an oleh &arena berbagai hal! ma&a

&lasifi&asi lupus nefritis dapat dila&u&an penilain berdasar&an panduan K;1

(lihat tabel ?)

#? Aanifestasi linis

>enal disease can be asymptomatic especially in patients with class $ and

$$ and renal symptoms appear when patients are in nephritic stage or develop

nephrotic syndrome 6linical features generally correlate with disease activity

and class of L0 (Table $$$) (:# lupus)

The most common clinical sign of renal disease is proteinuria! but

hematuria! hypertension! varying degrees of renal failure! and an active urine

sediment with red blood cell casts can all be present -lthough significant

renal pathology can be found on biopsy even in the absence of ma'or

abnormalities in the urinalysis! most nephrologists do not biopsy patients

until the urinalysis is convincingly abnormal The extrarenal manifestations

of lupus are important in establishing a firm diagnosis of systemic lupus

because! while serologic abnormalities are common in lupus nephritis! they

are not diagnostic (harrison)

#"+ 4iagnosis

5rinalysis

?

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$t is the most important test for detection as well as

monitoring of L0 -n early morning! midstream! clean catch

and non refrigerated specimen is analysed for evidence of

proteinuria and active urinary sediments The characteristic

findings on urinalysis are shown in Table $M

NTelescopic urine sedimentsO ie all types of cells and casts

in urine are found in severe proliferative glomerular and

tubular disease

>enal biopsy

$nformation about K;1 class! disease activity and prognosis

can be obtained by this investigation -tleast "+ glomeruli

should be examined for conclusive results

$ndications of renal biopsy are

- 0ephritic urinary sediments

B lomerular hematuria with P +: gm day proteinuria

6 lomerular hematuria with D +: gm day proteinuria

with reduced 6 and

4 positive -nti%ds40-

E

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4 eduction in levels of 6 and 69 on serial

monitoring predict flare

-SSESSAE0T 12 4$SE-SE -6T$M$TQ

Treatment of L0 depends upon the severity of disease and

K;1 class of L0 The assessment of disease activity is as

shown in Table M

(:# lupus)

""

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(unc)

#""

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most important and effective method to detect and monitor disease renal

activity To assure its Guality! several steps have to be ta&en These include

expeditious examination of a fresh! early morning! midstream! clean catch!

non%refrigerated urine specimen7 and flagging of specimens from patients at

substantial ris& of developing L0 to ensure careful examination at central

laboratories ;aematuria (usually microscopic! rarely macroscopic) indicates

inflammatory glomerular or tubulointerstitial disease Erythrocytes are

fragmented or misshaped (dysmorphic) ranular and fatty casts reflect

proteinuric states while red blood cell! white blood cell! and mixed cellular

casts reflect nephritic states Broad and waxy casts reflect chronic renal

failure $n severe proliferative disease! urine sediment containing the full

range of cells and casts can be found (Rtelescopic urine sediment) as a result

of severe glomerular and tubular ongoing disease superimposed on chronic

renal damage >enal biopsy rarely helps the diagnosis of lupus! but is the best

way of documenting the renal pathology (figure "+) $n the absence of renal

abnormalities! renal biopsy has nothing to offer and should not be performed

(sample! #+"#)

-ntids40- antibodies that fix complement correlate best with the

presence of renal disease ;ypocomplementemia is common in patients with

acute lupus nephritis (*+=?+,) and declining complement levels may herald

a flare >enal biopsy! however! is the only reliable method of identifying the

morphologic variants of lupus nephritis (harrison)

#"# Tatala&sana

Both 6lass $ and $$ lesions are typically associated with minimal renal

manifestation and normal renal function7 nephrotic syndrome is rare

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6lass $$$ describes focal lesions with proliferation or scarring! often

involving only a segment of the glomerulus (2ig 9%"+) 6lass $$$ lesions have

the most varied course ;ypertension! an active urinary sediment! and

proteinuria are common with nephrotic%range proteinuria in #:=, of

patients Elevated serum creatinine is present in #:, of patients

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azathioprine 0ephrologists tend to avoid prolonged use of cyclophosphamide

in patients of childbearing age without first ban&ing eggs or sperm

The 6lass M lesion describes subepithelial immune deposits producing a

membranous pattern7 this category of in'ury is treated li&e 6lass $M

glomerulonephritis Sixty percent of patients present with nephrotic syndrome

or lesser amounts of proteinuria

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(610T>E>-S)

".

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"*

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(re&omendasi)

$ndicators of remission

" $nactive urinary sediments in the absence of extrarenal

disease

# 0ormalization of complement levels for at least . months

when patients are off immunosuppressive therapy except

low dose 6S

Therapy to be continued for at least " year beyond remission

Treatment of renal flare" Aild to moderate nephritic flare%;igh dose 6S if no

remission treat as severe or 6S U-V-AA2

# Severe nephritic % Aonthly 6Q pulses plus A< or 6S U -V-

AA2

T>E-TAE0T 12 61A1>B$4 6104$T$10S

;ypertension (;T)

;T can lead to progressive renal failure F cardiovascular

morbidity Target B< should be D "#+*: mm of ;g F D ""+*+

mm of ;g in presence of proteinuria -6E inhibitors ->Bs

with diuretics are preferred as they reduce proteinuria

4yslipidemia

$t increases ris& of atherosclerosis F cardiovascular

mortality Target L4LD "++mgdl! TD ":+ mgdl

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4

$n patients with rapidly deteriorating renal functions

F nephritis pulse A< U 6Q / to "+ hrs before dialysis

$mmunosuppressive therapy to be discontinued if creatinine

P : mgdl! inactive urinary sediments F renal biopsy

suggestive of scarring F atrophy or contracted renal size

>enal transplantation

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#" enal survival is estimated between /, and ?#,at : years and

*9,=/9, at "+ years Several factors have been associated with an adverse

renal prog%nosis in patients with SLE! including demographic"#=

":clinical!biochemical! genetic! immunological and histopathological aspects

and antiphospholipid syndrome! but none aloneseems to be determinant

-mong the predictors of poor renal outcomes in the shortterm (.=#9 months)!

high titers of antibodies to double%stranded40- (anti%ds40-)! low serum

complement! age at presentation(children! adolescents and the elderly)

thrombocytopenia andhypoalbuminemia may be found ;istologically!

subendothelialdeposits are the strongest predictor! since the persistence in

thenumber of subendothelial deposits correlates with impaired renalfunction

2actors associated with poor long%term results are hyper%tension! hematuria!

duration of the disease and lac& of response totreatment Marious factors

affecting renal outcome were described -mongthe demographic variables! it

has been reported that a 'uvenilelupus onset and in young adults! those under

9+ years! havea higher number of exacerbations (S#"*! #+"9)

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9 -ntiphospholipid antibody syndrome

: 4iffuse proliferative disease

.

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