Staci Smith DO
Nephrology Grandview Hospital
 Overview


of Lupus
Types of lupus
History
 Common
manifestations
 SLE Nephritis




WHO classification
Biopsy Indications
Biopsy Findings
Treatment
 hematuria
 proteinuria
 red
blood cell casts
glomerulonephritis
SLE
 Minimal Change Dz
 Membranous GN
 FSGS
 MPGN
 RPGN
 Ig A Nephropathy
 Anti GBM Dz



Goodpasture’s
Wegener’s
Hepatitis B, C
 AIDS
 Amyloidosis
 HSP
 Cryoglobulinemia
 Vasculitides
 Poststrept/ Poststaph
GN

 red
cell casts
virtually diagnostic of
glomerulonephritis or
vasculitis
 only one needed
 absence does not exclude
diagnosis

Systemic Lupus:
 most common and affects major organs
 Discoid Lupus:
 affects only the skin
 not fatal, but can cause severe scarring
 Drug-induced Lupus:
 is systemic Lupus caused by medications
 when the medicine is stopped, the disease
goes away

 autoimmune
disorder
 multisystem microvascular inflammation
 defined by clinical picture and generation of
autoantibodies

mostly against double stranded DNA

autoantibodies

mostly against double stranded DNA and the Smith
antigen
 Ab to Smith (Sm) antigen is very specific for SLE
 25% of patients



not known when Lupus first appeared
 Hippocrates noted similar diseases in Ancient Greece
facial rash that resembles the markings of a wolf
1851 French-man named Pierre Cazenave


first clinical records
more than 1.4 million Americans are affected by SLE
Serological Tests to Aid Diagnosis of SLE
Test
% positive in SLE
ANA
95%
Anti-nDNA
60%
Anti-nRNP
80%
Anti-Sm
20%
Anti-Ro
30%
Anti-La
10%
Rim
Diffuse
Nucleolar
Speckled
 American



College of Rheumatology
presence of 4 of 11 criteria can establish SLE Dx
96% sensitive and specific
updated 1995

Serositis –pleuritis,
pericarditis
 Oral ulcers - painless
 Arthritis – 2 or more
peripheral joints
 Photosensitivity
SOAP
BRAIN
MD

Blood Abnormalities –
thrombocytopenia, lymphopenia,
lymphopenia (x2),hemolytic anemia
 Renal – casts, proteinuria,
hematuria
 ANA positive
 Immune Abnormalities – ANA, Anti
DS DNA, Smith Ag, false (+) syphilis
 Neurologic - seizures, psychosis
Malar Rash- spares nasolabial folds
 Discoid Rash – scaling,scaring

 Lupus


nephritis
one of the most serious manifestations of SLE
typically arises within 5 years of diagnosis

commonly within the first 6 to 36 months
 Renal
failure rarely occurs before American
College of Rheumatology classification
criteria are met.
 total
incidence of renal involvement among
patients with SLE exceeds 90 %
 abnormal urinalysis




with or without an elevated Cr
in approximately 50% at diagnosis time
proteinuria present in 80%
40% have hematuria and/or pyuria
 ‘Silent’



lupus nephritis
normal urinalysis
no proteinuria
normal serum creatinine levels
 However,
renal biopsy reveals pathological changes
 Six
types of renal involvement with SLE
 Why do renal biopsy?


to determine stage of disease
histological evidence is present in most SLE pts
even if they do not have clinical manifestations of
renal disease
 Pattern


of glomerular injury
related to the site of formation of the immune
deposits
is primarily due to anti DS DNA
Indications for Renal Biopsy with SLE Patients
Proteinuria of >1g/day
conventionally 1-2g/day
Less proteinuria does not preclude biopsy if major serologic abnormalities,
especially hypocomplementemia
At the other extreme, the presence of full-blown nephrotic and nephritic syndromes
Progressive azotemia
Decreasing renal function in assocation with active urinary sediment
Ambiguity or inconsistency of data
Lupus nephritis of indeterminate duration, severity and potential responsiveness
Overlapping clinical features
Situations where clinical and laboratory data are compatible with different classes
of lupus nephritis, for which different approaches to management are warranted
Redirection of therapy
Partially treated or incompletely responsive lupus nephritis
Morphological Classification of Lupus Nephritis
(modified WHO Classification)
Class
Biopsy finding
I
Normal glomerulus
II
Pure mesangial alteration
III
Focal proliferative glomerulonephritis
IV
V
Diffuse proliferative
glomerulonephritis
Membranous glomerulopathy
VI
Advanced glomerulosclerosis
light micrograph
 capillary lumens open
 glomerular capillary wall thickness



similar to that of the tubular basement membranes
mesangial cells and matrix are located in the
central or stalk regions of the tuft
segmental areas of
increased mesangial
matrix and cellularity
 light micrograph

 Divided

Class III (A):


active lesions
Class III (A/C):


by active and/or chronic lesions:
active and chronic pathology
Class III (C):


chronic inactive lesions with scarring
a.k.a. focal sclerosing lupus nephritis
usually associated
with subendothelial
deposits
 areas of cellular
proliferation
 thickening of
glomerular capillary
 “wire loop”

 subendothelial
deposits
 deposition of immunoglobulins and
complement

results in thickening of the glomerular
capillary wall
 subsets


segmental = < 50% of glomeruli
diffuse = >50% of glomeruli
subendothelial
deposits
 thickening of
glomerular capillary
wall

Class five
 the one form of lupus nephritis that may present with
no other clinical or serologic manifestations of SLE
 typically presents with signs of nephrotic syndrome
 microscopic hematuria and hypertension also may be
seen
 Cr concentration is usually normal or only slightly
elevated

 sclerosis
of more than 90% of
glomeruli
 represents healing of previous
inflammatory injury

as well as the advanced stage of chronic
class III, IV, or V lupus nephritis
 immunosuppressive
therapy is NOT
likely to be beneficial
 diffuse
(class IV) or severe focal (class III)
proliferative glomerulonephritis,
 severe or progressive membranous lupus
(class V)
 marked nephrotic syndrome
 rising serum creatinine
 membranous in association with class III or
class IV disease

mixed disease
 No
internal organ involvement
 First line: NSAID’s
 Cyclooxygenase-2 specific inhibitor

may induce thrombotic risk in patients with
antiphospholipid antibodies
 Low

dose hydroxychloroquine
200mg twice a day
 Manifestations
glucocorticoids



not often responsive to
Thrombosis—includes strokes
Glomerulonephritis
Resistant thrombocytopenia or hemolytic
anemia
 Previously
untreated patients
 Active lupus nephritis or severe
manifestations

decreased renal function and /or high-grade
proteinuria
 First

line: high doses of corticosteroids
about 1mg/kg/day
 Cytotoxic
drugs
drugs or other immunosuppressive
 Active
and severe GN depsit high dose
steroids
 Responded
to corticosteroids but require
an unacceptably high dose to maintain a
response.
 Side effects from corticosteroids
 Chronic damage on a renal biopsy
requires 6–12 months to work well
 1–3 mg/kg/day(initial dose)
 1–2 mg/kg/day(maintenance dose)
 Advantage:probably reduces flares,
reduces renal
scarring, reduces glucocorticoid dose
requirement
 Side effects: Bone marrow suppression,
leukopenia, infection(herpes zoster),
infertility, malignancy, early menopause,
hepatic damage, nausea

 Advantage

reduces flares, reduces renal
scarring, reduces glucocorticoid doses
 Side

effects
bone marrow suppression, leukopenia,
infection, malignancy, nausea,etc
requires 2–16 weeks to work well
 Initial dose:1-3 mg/kg/day orally or 8–20
mg/kg intravenously once a month
plus mesna
 Maintenance dose:0.5–2 mg/kg/day orally or 8–
20mg/kg intravenously every 4–12 wks
 Mesna

 mycophenoalte
mofetil may be an
alternative to cyclophosphamide as initial
therapy
 particularly among patients who refuse or
cannot tolerate cyclophosphamide
 Biggest side effect is diarrhea, also
myelosuppression
 fewer side effects than cyclophosphamide
 interferes
with the activation and
differentiation of B cells
 lysis mediated by:



Complement
Fc receptor-bearing cytotoxic cell
Inducing apoptosis
 selective
transient depletion of the CD20+ Bcell subpopulation
 Avoid
possible disease triggers-sulfa
antibiotics, sun, high estrogen-containing
birth control pills,alfalfa sprouts
 Prevent atherosclerosis
 Prevent osteoporosis
 Prevent infection
 Prevent progression of renal disease
 Prevent clots in patients with
antiphospholipid antibodies
 hematuria
 proteinuria
 red
blood cell casts
glomerulonephritis
 autoimmune
disorder
 multisystem microvascular inflammation
 defined by clinical picture and generation of
autoantibodies

mostly against double stranded DNA

Serositis –pleuritis,
pericarditis
 Oral ulcers - painless
 Arthritis – 2 or more
peripheral joints
 Photosensitivity
SOAP
BRAIN
MD

Blood Abnormalities –
thrombocytopenia, lymphopenia,
lymphopenia (x2),hemolytic anemia
 Renal – casts, proteinuria,
hematuria
 ANA positive
 Immune Abnormalities – ANA, Anti
DS DNA, Smith Ag, false (+) syphilis
 Neurologic - seizures, psychosis
Malar Rash- spares nasolabial folds
 Discoid Rash – scaling,scaring

Morphological Classification of Lupus Nephritis
(modified WHO Classification)
Class
Biopsy finding
I
Normal glomerulus
II
Pure mesangial alteration
III
Focal proliferative glomerulonephritis
IV
V
Diffuse proliferative
glomerulonephritis
Membranous glomerulopathy
VI
Advanced glomerulosclerosis
Happy Thanksgiving !