Lupus neprhitis

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Lupus neprhitis

• Staci Smith DO
• Nephrology Grandview Hospital

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Todays objectives

• Overview of Lupus
• Types of lupus
• History
• Common manifestations
• SLE Nephritis
• WHO classification
• Biopsy Indications
• Biopsy Findings
• Treatment

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Differential Diagnosis

• hematuria
• proteinuria glomerulonephritis
• red blood cell casts

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DDx Glomerulonephritic Dz

• SLE
• Minimal Change Dz
• Membranous GN
• FSGS
• MPGN
• RPGN
• Ig A Nephropathy
• Anti GBM Dz
• Goodpastures
• Wegeners

• Hepatitis B, C
• AIDS
• Amyloidosis
• HSP
• Cryoglobulinemia
• Vasculitides
• Poststrept/ Poststaph GN                      
                         
•          

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Red Blood Cell Casts

• red cell casts
• virtually diagnostic of glomerulonephritis or
  vasculitis
• only one needed
• absence does not exclude diagnosis

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Types Of Lupus

• 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

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What is Systemic Lupus Erythematous?

• autoimmune disorder
• multisystem microvascular inflammation
• defined by clinical picture and generation of
  autoantibodies
• mostly against double stranded DNA

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Pathogenesis of SLE

• autoantibodies
• mostly against double stranded DNA and the Smith
  antigen
• Ab to Smith (Sm) antigen is very specific for SLE
• 25 of patients

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History of SLE

• 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

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SLE Manifestations
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SLE Dermopathy
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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
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ANA Antibodies
Rim
Diffuse
Speckled
Nucleolar
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Lupus Criteria

• American College of Rheumatology
• presence of 4 of 11 criteria can establish SLE Dx
• 96 sensitive and specific
• updated 1995

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American College of Rheumatology Criteria for
Diagnosis of SLE

• Serositis pleuritis, pericarditis
• Oral ulcers - painless
• Arthritis 2 or more peripheral joints
• Photosensitivity

• 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

SOAP BRAIN MD
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Lupus and the Kidney

• 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.

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Lupus and the Kidney

• 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

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Lupus and the Kidney

• Silent lupus nephritis
• normal urinalysis
• no proteinuria
• normal serum creatinine levels
• However, renal biopsy reveals pathological changes

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Lupus Nephritis

• 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

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Indications for Renal Biopsy with SLE Patients
Proteinuria of gt1g/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
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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
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Normal Glomerulus

• 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

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Mesangial Proliferative Lupus Nephritis Class II

• segmental areas of increased mesangial matrix and
  cellularity
• light micrograph

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Focal Proliferative Nephritis (Class III) Subsets

• 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

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Focal Proliferative Nephritis (Class III)

• usually associated with subendothelial deposits
• areas of cellular proliferation
• thickening of glomerular capillary
• wire loop

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Diffuse Proliferative NephritisClass IV

• subendothelial deposits
• deposition of immunoglobulins and complement
• results in thickening of the glomerular capillary
  wall
• subsets
• segmental lt 50 of glomeruli
• diffuse gt50 of glomeruli

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Diffuse Proliferative NephritisClass IV

• subendothelial deposits
• thickening of glomerular capillary wall

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Membranous Nephritis

• 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

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Sclerosing Nephritis Class VI

• 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

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• 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

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Therapy for lupus patients with arthritis

• 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

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• Manifestations not often responsive to
  glucocorticoids
• Thrombosisincludes strokes
• Glomerulonephritis
• Resistant thrombocytopenia or hemolytic anemia

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Therapy for patients with lupus nephritis

• 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

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The indications of cytotoxic drugs use in the
treatment of lupus nephritis

• 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

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Use of Cytotoxic Drugs in SLE Azathioprine

• requires 612 months to work well
• 13 mg/kg/day(initial dose)
• 12 mg/kg/day(maintenance dose)
• Advantageprobably 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

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• Advantage
• reduces flares, reduces renal
  
  
  
  scarring, reduces
  glucocorticoid doses
• Side effects
• bone marrow suppression, leukopenia, infection,
  malignancy, nausea,etc

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Use of Cytotoxic Drugs in SLE Cyclophosphamide

• requires 216 weeks to work well
• Initial dose1-3 mg/kg/day orally or 820
  
  mg/kg intravenously once a month
  
  plus mesna
• Maintenance dose0.52 mg/kg/day orally or
  820mg/kg intravenously every 412 wks
• Mesna

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• 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

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Rituximab

• 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 B-cell
  subpopulation

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Other management principles in the treatment of
lupus patients

• 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

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Differential Diagnosis

• hematuria
• proteinuria glomerulonephritis
• red blood cell casts

42
What is Systemic Lupus Erythematous?

• autoimmune disorder
• multisystem microvascular inflammation
• defined by clinical picture and generation of
  autoantibodies
• mostly against double stranded DNA

43
American College of Rheumatology Criteria for
Diagnosis of SLE

• Serositis pleuritis, pericarditis
• Oral ulcers - painless
• Arthritis 2 or more peripheral joints
• Photosensitivity

• 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

SOAP BRAIN MD
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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
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Happy Thanksgiving !