Lupus Nephritis Treatment

Renal involvement - 40-85% 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

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

<Recommendation> Six monthly IV cyclophosphamide pulse for initial Tx (0.5g/m2->1.0g/m2) Concurrent administration six monthly pulse IV MPD (500-1000mg) Oral PDL (1.0mg/kg), tapering to 5-10mg/d => Five year renal survival : 60-90%

Pulse corticosteroids for lupus nephritis MPD pulse Tx (500-1000mg for 3 days) rapidly immunosuppressing pts with life threatening SLE Side effect Infection, neuropsychiatric complication (Sz, mania, psychosis, hemiplegia), arthralgia, osteoporosis

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

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

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)

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