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 glomerulonephritis
red blood cell casts
 SLE Hepatitis B, C
Minimal Change Dz AIDS
Membranous GN Amyloidosis
FSGS HSP
MPGN Cryoglobulinemia
RPGN Vasculitides
Ig A Nephropathy Poststrept/ Poststaph
Anti GBM Dz GN
Goodpastures
Wegeners
 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, Blood Abnormalities
pericarditis thrombocytopenia, lymphopenia,
Oral ulcers - painless
lymphopenia (x2),hemolytic anemia
Renal casts, proteinuria,
Arthritis 2 or more
peripheral joints hematuria
ANA positive
Photosensitivity
Immune Abnormalities ANA, Anti
DS DNA, Smith Ag, false (+) syphilis
Neurologic - seizures, psychosis
SOAP
Malar Rash- spares nasolabial folds
BRAIN Discoid Rash scaling,scaring
MD
 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.
 totalincidence 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 Diffuse proliferative
glomerulonephritis
V 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 by active and/or chronic lesions:
Class III (A):
active lesions
Class III (A/C):
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
 sclerosisof 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: NSAIDs
Cyclooxygenase-2 specific inhibitor
may induce thrombotic risk in patients with
antiphospholipid antibodies
Low dose hydroxychloroquine
200mg twice a day
 Manifestations not often responsive to
glucocorticoids
Thrombosisincludes 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 or other immunosuppressive
drugs
 Activeand 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 612 months to work well
13 mg/kg/day(initial dose)
12 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 216 weeks to work well
Initial dose:1-3 mg/kg/day orally or 820
mg/kg intravenously once a month
plus mesna
Maintenance dose:0.52 mg/kg/day orally or 8
20mg/kg intravenously every 412 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
selectivetransient depletion of the CD20+ B-
cell 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 glomerulonephritis
red blood cell casts
 autoimmune disorder
multisystem microvascular inflammation
defined by clinical picture and generation of
autoantibodies
mostly against double stranded DNA
 Serositis pleuritis, Blood Abnormalities
pericarditis thrombocytopenia, lymphopenia,
Oral ulcers - painless
lymphopenia (x2),hemolytic anemia
Renal casts, proteinuria,
Arthritis 2 or more
peripheral joints hematuria
ANA positive
Photosensitivity
Immune Abnormalities ANA, Anti
DS DNA, Smith Ag, false (+) syphilis
Neurologic - seizures, psychosis
SOAP
Malar Rash- spares nasolabial folds
BRAIN Discoid Rash scaling,scaring
MD
Morphological Classification of Lupus Nephritis
(modified WHO Classification)

Class Biopsy finding

I Normal glomerulus
II Pure mesangial alteration
III Focal proliferative glomerulonephritis
IV Diffuse proliferative
glomerulonephritis
V Membranous glomerulopathy
VI Advanced glomerulosclerosis
Happy Thanksgiving !