LECTURE 2 Management LUPUS (GLOMERULONEPHRITIS) -LN

GLOMERUNEPHRITIS 1) Plasma exchange to remove circulating GN-common feature of SLE

Rapidly progressive glomerulonephritis
= syndrome with
1) Glomerular hematuria (RBC cast /
dysmorphic RBC)
2) Rapidly developing acute kidney failure
over weeks to months
3) Focal glomerular necrosis with or without
glomerular crescent development on renal
biopsy
Particular Nephritic syndrome
1) ↑ ESR, CRP
2) Arterial hypertension infrequent
3) Mild/moderate edema
4) Untreated → end-stage kidney disease in
weeks/months … 2 years
1. LINEAR IF PATTERN RPGN
Anti-GBM antibody RPGN
1) 15 – 20% RPGN and <5% all GN
2) Linear deposit in IF
3) Fibrinoid necrosis of GBM / crescentic GN
4) Goodpasture syndrome
5) Anti-GBM disease ()renal restricted anti
GBM-RPGN
Symptomology
1) Renal manifestation
a. Oliguria
b. Hematuria
c. Proteinuria < 3.5g/24h
d. RPGN
2) Hemorrhagic alveolitis
a. Concomitant with GN or absent
b. Favorized by smoking, infection,
uremia, fluid overload
c. Frequent cause of death
anti-GBM antibodies
2) I.V pulse-therapy with steroids to suppress
inflammation from antibody already
deposited in the tissue
a. Methyl-prednisolone 0.5g/day iv
b. 3 days + cyclophosphamide iv 500-
600mg/m2 to suppress new antibody
synthesis
Prognosis is directly related to extent of
glomerular damage at the initiation of treatment
- Oliguria occurs or serum creatinine rises
> 600 – 700 mmol/l (> 8 mg/dl), renal
failure is usually irreversible
- Once active disease is treated this
condition unlike other autoimmune
diseases does not follow
remitting/relapsing course
2. GNANULAR IF PATTERN GN
IMMUNE COMPLEXES (IC) RPGN
1) Idiopathic IC RPGN
2) Secondary
a. Postinfectious
(staphylococci/streptococci)
b. Connective tissue disease (lupus)
c. Henoch-Schönlein purpura
(immunoglobulin A, systemic
vasculitis)
3) Associated with other primary GN
a. Immunoglobulin A nephropathy (no
vasculitis)
b. Mixed cryoglobulinemia
c. MPGN
*CIC positive, low serum C3/C4
- Immune complex deposition
- In situ formation
Associated with deposits
- Blood vessels
- Tubular BM
- Intestitium
Complement deposits → inflammation
Renal pathology of lupus nephritis Class I-VI
Class I - Minimal mesangial lupus nephritis
normal on light microscopy. Asymptomatic.
Class II – Mesangial proliferative LN,
Clinically, there is mild renal disease.
Class III – Focal LN (involving <50% of
glomeruli) Clinical ~hematuria+proteinuria;~
20%LN
Class IV – Diffuse LN (involving
>50% of glomeruli; Subendothelial deposits are
present
Class V – Membranous LN 10–20% of patients.
Can occur in combination with class III or IV.
Good prognosis
Class VI – Advanced sclerosing LN (≥90%
globally sclerosed
Type I lupus nephritis – no requirement for
specific treatment
Type II benign – treated w/ hydroxychloroquine
Immunosuppressive agents
Type III Type IV Type V
Steroids and high-dose of cyclophosphamide or
mycophenolate mofetil (MMF)
Maintenance of remission with MMF or
azathioprine 2mg/kg
B-cell depletion with rituximab
2.B IgA VASCULITIS (HENOCH-
SCHÖNLEIN PURPURA)
Clinical presentation
1) Palpable purpura
a. Necrotizing vasculitis
b. Blood extravasation from small vessels
of dermis
2) Joint pain
3) Blood in urine
4) Colicky pain abdomen
*<10 years old children follows with upper
respiratory infection
HSP
1) Small-vessel vasculitis
2) Deposition of IgA in skin, mucous
membrane, kidney, abdominal vessels
3) Most common vasculitis in childhood 2-
11yo
4) Usually preceded by URI
5) 95% full recovery after 3-4 weeks
6) Adult’s symptoms are worse
7) Renal failure rare but possible
Clinical tetrad
1) Non-thrombocytopenia, palpable purpura
2) Abdominal pain – colicky pain (ileoileal),
heme positive stool
3) Hematuria – microscopic hematuria,
proteinuria, elevated BUN/creatine
4) Arthritis
IgA Nephropathy
Etiology
1) Idiopathic
a. Exclusively kidney disease
b. Henoch-Schönlein purpura (systemic)
2) Secondary
a. Liver disease: chronic hepatitis / toxic-
alcoholic liver cirrhosis, biliary stasis
b. Gastrointestinal diseases: celiac disease,
Crohn's disease, adenocarcinomas
c. Respiratory diseases: PIF, obstructive
bronchiolitis, bronchopulmonary
adenocarcinomas
d. Skin diseases: herpetiform dermatitis,
mycosis fungoides, leprosy, psoriasis
e. Eye diseases: episcleritis, anterior uveitis
f. Rheumatological diseases: Sero-negative
spondylitis, recurrent polychondritis,
Sjögren
Clinical features
1) Asymptomatic microscopic hematuria
/recurrent macroscopic hematuria
following upper respiratory / GI viral
infection
2) Proteinuria
3) Tends to occur in children and young male
4) Serum creatine ↑
5) Hypertension
6) ACE gene polymorphism
7) Tubulointerstitial fibrosis on renal biopsy
Management
1) HT + proteinuria → ACE inhibitor to
reduce proteinuria
2) Proteinuria of > 1-3g/day mild glomerular
changes and normal renal function →
corticosteroids to ↓ proteinuria
3) Patient with higher risk – proteinuria >
750mg/day and GFRe <60ml/min →
corticosteroids + immunosuppressants –
prednisolone or/with cyclophosphamide
4) Budesonide
5) Tonsillectomy can recuce proteinuria and
hematuria
6) SGLT2i
3.NEGATIVE IF RPGN
Pauci-immune: Anca positive RPGN
Types
1) GPA- Granulomatosis with
polyangiitis(Wegener granulomatosis) GPA
a. Presence of upper airway lesion,
pulmonary infilters
b. Patients presents w/ sinusitis,
pulmonary hemorrhage, renal failure
c. Lungs show granulomatous
inflammation
d. Positive ANCA (cANCA)
2) Microscopic polyangiitis (MPA)
a. Pulmonary infiltrates and RPGN +
musculoskeletal/neuropathy/CNS
system abnormalities
b. Vessels are involved
c. 80-90% ANCA positive (pANCA)
3) Renal-limited necrotizing crescentic
glomerulonephritis (NCGN)
4) Churg-Strauss syndrome
a. Allergic asthma
b. Eosinophilia
c. 70-90% NACA positive (pANCA)
2 major staining patterns
1) Cytoplasmic ANCA – cANCA
8) Perinuclear pattern ANCA – pANCA
Renal histology (KUMAR)
Gold standard for diagnosis and prognostication
of NACA-associated GN
4 general categories of lesions
1) focal (≥50% normal glomeruli not affected
by the disease process)
2) crescentic (≥50% of glomeruli with cellular
crescents)
3) mixed (a heterogeneous glomerular
phenotype-no glomerular feature
predominates)
4) sclerotic (≥50% of glomeruli with global
sclerosis).
Clinical manifestation
1) Brutal onset – Ac Anti MBG/Pauci immune
a. Oliguria + hematuria/casts + edema
b. Malaise, fever, arthralgias, myalgias,
anorexia, weight loss
2) Onset – rheumatoid purpura
a. Erythema/ purpura
b. Arthralgia
c. Abdominal pain, melena
3) Insidious onset
a. Hematuria, proteinuria
b. Accidental discovery of renal failure
(RF ↑ serum creatine)
4) Onset in 2 steps – CIC
a. ↑ proteinuria, casts, ESR elevated
b. Rapidly progressive RF
CLINICAL MANIFESTATION IN
VASCULITIS
Skin
1) Leukocytoclastic vasculitis lower
extremities
2) Necrotizing arteritis – painful erythematous
nodulus, focal necrosis, ulceration, livedo
reticularis
3) Nail fold infracts can be present
Musculoskeletal 60%
1) Pain elevated CPK
2) Arthritis symmetrical, migratory all small
joints
3) Arthralgias common, not marker for active
vasculitis
Gastro
1) Arteritis result in ischemic ulceration in GI
tract → causing pain, bleeding → occult
2) GI ischemia – pancreatitis
3) GI involvement occurs 50% of patient w/
ANCA
Renal
1) Biopsy → proliferative necrotizing
crescentic glomerulonephritis
2) Microscopic hematuria + casts +/-
proteinuria
3) The prevalence rate of renal disease is 90%
for those with microscopic polyangiitis,
80% for those with Wegener
granulomatosis, and 45% for those with
Churg-Strauss disease
Respiratory
1) Range between fleeting focal infiltrates
alveolar capillaritis → massive pulmonary
hemorrhage and hemoptysis
2) Most deadly complication of ANCA disease
3) Sinusitis, otitis media,, ulcers in nasal
mucosa, subglottic stenosis
4) Ocular – iritis, uveitis, conjunctivitis
5) Nervous system – mononeuritis multiplex
caused by inflammation of the epineural
arteries, seizures (CNS meningeal vessels)
Laboratory abnormalities
1) Hemogram – anemia due to CKD or
bleeding from GI tract; eosinophilia >13%
(suggest Churg-Strauss disease)
2) Serum electrolytes, BUN, creatinine, LDH,
CPK
3) Liver function tests: ↑ n serum creatinine
level, tissue enzyme elevated in myalgias
4) Urinalysis w/ microscopy : proteinuria
present but 2-3g/24h; microscopy hematuria
+ red cell casts
Laboratory investigations
1) ESR > 100 div/1h, CRP ↑
2) ANA not positive in ANCA-associated
disease, High ANA titer → SLE
3) Cryoglobulins +
4) Hepatitis B, C + HIV testing
5) Urine and serum protein electrophoresis –
light-chain disease or overt multiple
myeloma
Imaging studies
1) To rule out obstructive uropathy with acute
or chronic renal failure
2) Hyperechogenic symmetrical reduced
cortex = CGN
3) Quasinormal kidney + edematous,
hypertrophic pyramids = RPGN
Medical care – induction therapy
1) Methylprednisolone 7mg/kg/day iv; 3 days
→ oral prednisolone 1mg/kg/day, 3 weeks
oral prednisone 2mg/kg/every2days 3kk
2) Cyclophosphamide oral/iv
a. iv 0.5g/m2 + oral 2mg/kg adjusted to
according to 2 week leukocyte count (3-
4k/ul)
Medical care – maintenance therapy
1) Azathioprine for cyclophosphamide – 3-6
months (dose: 2mg/kg oral – 6/12/24kk)
2) Mycophenolate mofetil (MMF) – (dose:
1.5-2g/day for 3-6 kk)
3) Plasmapheresis – for patient with severe
renal failure or with high antibodies/CIC
levels despite immunosuppression
Serum creatinine > 6mg/dl

Treatment options
1) Rituximab
2) Fulminant disease require
immunosuppression with adjuvant plasma
exchange/ iv pulsed methylprednisolone –
1g/day for 3 days

Evolution/Prognosis
Evolution
1) Frequent relapses
2) Medium interval for relapses – 2.2 years
(40 days – 15 years)
Prognosis – 2 years
1) End-stage renal disease
2) Death
3) Infections, neoplasia

*colonization of upper respiratory tract with

staphcoccus aureus increases risk of relapse →
treatment with sulfamethoxazole/ trimethoprim
reduces relapse rate

* relapse after complete withdrawal of IS occurs

relatively frequently, so long-term, relatively
low-dose immunosuppression may be necessary