EFFECT OF MAINTENANCE TREATMENT WITH MYCOPHENOLATE MOFETIL ON CHRONIC INFLAMMATORY STATUS IN PROLIFERATIVE LUPUS NEPHRITIS

INTRODUCTION AND AIMS: Systemic Lupus Erythematosus (SLE) is associated with a high cardiovascular risk ascribed to a chronic inflammatory state. Conventional maintenance treatment consists of oral prednisone plus cyclophosphamide, azathioprine or cyclosporine A. The use of mycophenolate mofetil (MMF) has been recently proposed as a safe alternative to control disease activity. No data are available about any additional benefits on chronic inflammatory status. METHODS: A longitudinal study has been designed with 14 patients with proliferative lupus nephritis.(Figure 1) After diagnosis the patients underwent induction therapy and conventional maintenance treatment with oral cyclosporine A for one year. They were then switched to MMF and evaluated for 12 months. Disease activity index (SLEDAI 2K), antinuclear and anti double stranded DNA antibodies (Anti-dsDNA), renal function and proteinuria (expressed as urine Protein /Creatinine ratio) were measured in basal condition and every six months. Inflammatory status was also evaluated by measuring serum level of fibrinogen, C-reactive protein and uric acid. Interleukin 6 (IL-6) released by peripheral blood mononuclear cells was measured too. RESULTS: Disease activity: Both induction therapy and conventional maintenance therapy were able to decrease urine Protein/Creatinine ratio (P/C), though not reaching significance while treatment with MMF showed a significant decrease of P/C and increase of serum albumin levels (p < 0.001 vs basal values). Moreover MMF significantly decreased both SLEDAI-2K and Anti-dsDNA titer. (p < 0.001 vs basal values) No significant change has been showed in antinuclear antibodies, blood count, creatinine clearance, complement C3 and C4. Inflammatory status: Induction treatment and conventional maintenance treatment did not have effect on inflammatory markers, by contrast after 12 months of MMF therapy patients showed a significant decrease of serum levels of C-reactive protein, uric acid and IL-6 production were also significantly reduced (p<0.001 for IL-6), (Table 1). CONCLUSIONS: Maintenance therapy with prednisone and MMF is able to control disease activity and improve inflammatory status in patients with proliferative lupus nephritis. Behaviour of inflammatory markers all over the study (N=14) Basal Phase 1 Phase 2 Phase 3 Uric acid (mg/dl) 7.20±1.95 § 7.11±1.95 § 6.91±1.90* 5.98±1.42 CRP (mg/dl) 2.67±0.56* 2.22±0.35° 2.46±2.02* 0.70±0.59 IL-6 (pg/ml) 492.6±33.5 § 450.4±85.2 § 443.0±84.1 § 27.4±17.8 § §= p<0.001 vs MMF treatment. *=p<0.01 vs MMF treatment. °=p