1. Lupus Nephritis Treatment

2. Renal involvement
% of pts with SLE
Tx of lupus nephritis
- controversal, largely on class of injury and disease activity
< WHO classfication - histological changes >
I . Normal/minimal change (5%)
II . Mesangial proliferative (15 – 20 %)
III . Focal / segmental proliferative (20 – 30 %)
IV . Diffuse proliferative (45 – 60 %)
V . Membranous (10 – 15 %)
VI . Advanced & sclerosing GN

3. Treatment of lupus nephritis type IV
Induction Tx, maintenance Tx
High dose steroid (IV pulse Tx)
- effective at rapid control acute glomerular inflammation
Cyclophosphamide and azathioprine
- important adjuncts to steroid Tx
better long term preservation of renal function
MPM => Tx option in pts resistant to cyclophosphamide
Addition of plasma exchange to these Tx : no benefit

4. <Recommendation>
Six monthly IV cyclophosphamide pulse for initial Tx
(0.5g/m2->1.0g/m2)
Concurrent administration six monthly pulse IV MPD
( mg)
Oral PDL (1.0mg/kg), tapering to 5-10mg/d
=> Five year renal survival : 60-90%

5. Pulse corticosteroids for lupus nephritis
MPD pulse Tx ( mg for 3 days)
rapidly immunosuppressing pts with life threatening SLE
Side effect
Infection, neuropsychiatric complication
(Sz, mania, psychosis, hemiplegia), arthralgia, osteoporosis

7. Cyclophosphamide for lupus nephritis
Cyclophosphamide+steroid > sterold alone
Side effect
- Infection, bone marrow suppression, alopecia,
hemorrhagic cystitis, malignancy, gonadal toxicity
Premature ovarian failure (POF)
- 1/2 of all treated women
- age, cumulative dose
- older than 30 y : 100% , 20-30y : 50%
=> sustained amenorrhea => poor outcome of pregnancy

8. Lupus flare Frequently relapsing disease
Relapse occuring in 1/3-1/2 of pts overall
Relapse ?
- renewed clinical activity
- active urine sediment, proteinuria↑, Cr↑,
new finding of red cell and white cell casts
- Anti-dsDNA Ab↑, complement↓
Value of repeated biopsy?
optimal regimen to prevent fares? : unresolved issue

9. Mild relapses
- trial of oral prednisone or increase dose of prednisone
Moderate to severe relapse (no immunosuppressive Tx)
- reinstitution of initial induction regimen
Moderate to severe relapse (on immunosuppressive Tx)
- optimal Tx?, individualized care
- IV or oral cyclophosphamide,
- cyclosporine + mycophenolate or azathioprine
- more experimental regimens (rituximab)

10. Pharmacological therapy of lupus nephritis. JAMA 2005 Jun 22
To preserve fertility and avoid other toxicities of cyclophosphamide
in young SLE pts
-> therapy with mycophenolate mofetil
- MPM has emerged as an alternative to cyclophosphamide
Preservation of fertility and ovarian function and minimizing
gonadotoxicity in young women with systemic lupus erythematosus
treated by chemotherapy Lupus 2000:9
beneficial effect of GnRH-a co-treatment
- preservation of future fertility and ovarian function in every
young woman of reproductive age, exposed to alkylating agents