1. Staci Smith DO Nephrology Grandview Hospital
Lupus neprhitis
Staci Smith DO
Nephrology Grandview Hospital

2. Today’s objectives Overview of Lupus Common manifestations
Types of lupus
History
Common manifestations
SLE Nephritis
WHO classification
Biopsy Indications
Biopsy Findings
Treatment

3. Differential Diagnosis
hematuria
proteinuria glomerulonephritis
red blood cell casts

4. DDx : Glomerulonephritic Dz
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                                               
         

5. Red Blood Cell Casts red cell casts
virtually diagnostic of glomerulonephritis or vasculitis
only one needed
absence does not exclude diagnosis

6. 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

7. What is Systemic Lupus Erythematous?
autoimmune disorder
multisystem microvascular inflammation
defined by clinical picture and generation of autoantibodies
mostly against double stranded DNA

8. 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

9. 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

10. SLE Manifestations

11. SLE Dermopathy

12. Serological Tests to Aid Diagnosis of SLE
% positive in SLE
ANA
95%
Anti-nDNA
60%
Anti-nRNP
80%
Anti-Sm
20%
Anti-Ro
30%
Anti-La
10%

13. ANA Antibodies
Rim
Diffuse
Speckled
Nucleolar

14. Lupus Criteria American College of Rheumatology
presence of 4 of 11 criteria can establish SLE Dx
96% sensitive and specific
updated 1995

15. 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

16. 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.

17. 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

18. Lupus and the Kidney ‘Silent’ lupus nephritis
normal urinalysis
no proteinuria
normal serum creatinine levels
However, renal biopsy reveals pathological changes

19. 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

20. 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

21. (modified WHO Classification)
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

22. 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

23. Mesangial Proliferative Lupus Nephritis: Class II
segmental areas of increased mesangial matrix and cellularity
light micrograph
Can also be seen in Ig A nephropathy

24. 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

25. Focal Proliferative Nephritis (Class III)
usually associated with subendothelial deposits
areas of cellular proliferation
thickening of glomerular capillary
“wire loop”
Long arrow= cellular proliferation….short arrows are wire loops

26. Diffuse Proliferative Nephritis Class IV
subendothelial deposits
deposition of immunoglobulins and complement
results in thickening of the glomerular capillary wall
subsets
segmental = < 50% of glomeruli
diffuse = >50% of glomeruli

27. Diffuse Proliferative Nephritis: Class IV
subendothelial deposits
thickening of glomerular capillary wall

28. 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

29. 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

30. severe or progressive membranous lupus (class V)
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

31. Therapy for lupus patients with arthritis
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

32. Manifestations not often responsive to glucocorticoids
Thrombosis—includes strokes
Glomerulonephritis
Resistant thrombocytopenia or hemolytic anemia

33. 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

34. 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

35. Use of Cytotoxic Drugs in SLE : Azathioprine
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
zathioprine; requires 6–12 months
to work well
1–3 mg/kg/day
1–2 mg/kg/day
Probably reduces flares, reduces renal
scarring, reduces glucocorticoid dose
requirement
Bone marrow
suppression
<5
Leukopenia 15
Infections (herpes
zoster) 10
Malignancies
Infertility
Early menopause
Hepatic damage

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

37. Use of Cytotoxic Drugs in SLE: Cyclophosphamide
requires 2–16 weeks to work well
Initial dose:1-3 mg/kg/day orally or 8– 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

38. 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

39. 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

40. 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

41. 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

44. (modified WHO Classification)
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

45. Happy Thanksgiving !