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Proliferative Lupus Nephritis (proliferative + lupus_nephritis)
Selected AbstractsSynchronised therapy and high-dose cyclophosphamide in proliferative lupus nephritisJOURNAL OF CLINICAL APHERESIS, Issue 2 2002Maria Giovanna Danieli Abstract The aim of this open study was to compare the outcomes and side effects of plasmapheresis (PP) in patients with proliferative lupus nephritis treated with cyclophosphamide (Cyc) boluses. The study involved 28 consecutive patients. All of the patients met the ACR modified criteria for SLE and underwent a qualifying renal biopsy. In group I, patients were treated with synchronised therapy (PP, 50 ml/kg, followed by pulse Cyc, 750 mg/m2, repeated monthly for 6 months), whereas in group II, they were given only intermittent Cyc boluses (at the same dosage). The data were collected in the patients' records according to a standardised protocol. Patients were followed-up for a mean of 4 years. The disease-free survival was analysed using Kaplan-Meier estimated survival curves ([S(t)]). At the end of the 6-month treatment period, a statistically significant number of patients in group I (75%) was in complete remission in comparison to group II (31%) (P < 0.02), whereas at long-term follow-up, these percentages were similar (41% vs. 50%, P = n.s.). The main functional and immunological parameters showed a normalisation in both groups. The risk of a poor renal outcome significantly correlated with high serum creatinine levels at the onset of nephritis (P < 0.05). We documented a higher rate of infectious complications in group I. This study reports that synchronised therapy is useful in inducing a faster remission in patients with proliferative lupus nephritis. However, it is not superior to conventional therapy at long term follow-up analysis. Positive results should be reinforced by a long-term maintenance therapy. J. Clin. Apheresis 17:72,77, 2002. © 2002 Wiley-Liss, Inc. [source] Anti-DNA antibody induction of protein kinase C phosphorylation and fibronectin synthesis in human and murine lupus and the effect of mycophenolic acidARTHRITIS & RHEUMATISM, Issue 7 2009Susan Yung Objective To examine fibronectin (FN) expression in human lupus nephritis and the effect of anti-DNA antibodies on transforming growth factor ,1 (TGF,1) and FN synthesis in cultured human mesangial cells. The effects of mycophenolic acid (MPA) on this pathway, and the effects of mycophenolate mofetil (MMF) treatment in (NZB × NZW)F1/J mice were also studied. Methods Immunohistochemical analyses of renal biopsy samples from patients with active diffuse proliferative lupus nephritis were performed. Cultured human mesangial cells were incubated with human polyclonal anti-DNA antibodies, with or without MPA. (NZB × NZW)F1/J mice with active nephritis were randomized to receive either MMF (100 mg/kg/day) or vehicle treatment for 12 weeks. Results Glomerular FN expression was increased in patients with lupus nephritis, and it colocalized with IgG deposition. Anti-DNA antibodies induced protein kinase C, (PKC,), PKC,I, and PKC,II activation, increased levels of bioactive TGF,1, and increased FN synthesis in human mesangial cells (P < 0.001 for each comparison versus control conditions). Pretreatment of anti-DNA antibodies with exogenous DNA reduced their cellular binding and abrogated their induction of TGF,1 and FN synthesis. Inhibition of PKC activation in human mesangial cells prior to anti-DNA antibody stimulation had no effect on cell proliferation, but resulted in significantly reduced antibody-mediated TGF,1 secretion and FN synthesis. MPA treatment down-regulated PKC,, PKC,I, and PKC,II phosphorylation, reduced levels of TGF,1 bioactivation, and decreased FN synthesis and deposition into the extracellular matrix. MMF treatment in (NZB × NZW)F1/J mice resulted in a reduction in glomerular IgG deposition, PKC activation, and FN expression, as well as an amelioration of proteinuria. Conclusion Human polyclonal anti-DNA antibodies induce TGF,1 and FN synthesis in human mesangial cells through PKC activation, which is inhibited by MPA. [source] A short course of BG9588 (anti,CD40 ligand antibody) improves serologic activity and decreases hematuria in patients with proliferative lupus glomerulonephritisARTHRITIS & RHEUMATISM, Issue 3 2003Dimitrios T. Boumpas Objective CD40,CD40 ligand (CD40L) interactions play a significant role in the production of autoantibodies and tissue injury in lupus nephritis. We performed an open-label, multiple-dose study to evaluate the safety, efficacy, and pharmacokinetics of BG9588, a humanized anti-CD40L antibody, in patients with proliferative lupus nephritis. The primary outcome measure was 50% reduction in proteinuria without worsening of renal function. Methods Twenty-eight patients with active proliferative lupus nephritis were scheduled to receive 20 mg/kg of BG9588 at biweekly intervals for the first 3 doses and at monthly intervals for 4 additional doses. Safety evaluations were performed on all patients. Eighteen patients receiving at least 3 doses were evaluated for efficacy. Results The study was terminated prematurely because of thromboembolic events occurring in patients in this and other BG9588 protocols (2 myocardial infarctions in this study). Of the 18 patients for whom efficacy could be evaluated, 2 had a 50% reduction in proteinuria without worsening of renal function. Mean reductions of 38.9% (P < 0.005), 50.1% (P < 0.005), and 25.3% (P < 0.05) in anti,double-stranded DNA (anti-dsDNA) antibody titers were observed at 1, 2, and 3 months, respectively, after the last treatment. There was a significant increase in serum C3 concentrations at 1 month after the last dose (P < 0.005), and hematuria disappeared in all 5 patients with significant hematuria at baseline. There were no statistically significant reductions in lymphocyte count or serum immunoglobulin, anticardiolipin antibody, or rubella IgG antibody concentrations after therapy. Conclusion A short course of BG9588 treatment in patients with proliferative lupus nephritis reduces anti-dsDNA antibodies, increases C3 concentrations, and decreases hematuria, suggesting that the drug has immunomodulatory action. Additional studies will be needed to evaluate its long-term effects. [source] Choosing treatment for proliferative lupus nephritisARTHRITIS & RHEUMATISM, Issue 8 2002James E. Balow No abstract is available for this article. [source] | ||||||||||