BAB I - BAB 3.doc
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Transcript of BAB I - BAB 3.doc
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8/11/2019 BAB I - BAB 3.doc
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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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##