Recent advances in the management of lupus nephritis, together with earlier renal biopsy and selective use of aggressive immunosuppressive therapy, have contribut-ed to a favorable outcome in children and adolescents ...Recent advances in the management of lupus nephritis, together with earlier renal biopsy and selective use of aggressive immunosuppressive therapy, have contribut-ed to a favorable outcome in children and adolescents with systemic lupus erythematosus （SLE）. Neverthe-less, we believe that a more effective and less toxic treatment is needed to attain an optimal control of the activity of lupus nephritis. Recent published papers and our experiences regarding treatment of young patients with lupus nephritis using calcineurin inhibitors are re-viewed. Although it has been reported that intermittent monthly pulses of intravenous cyclophosphamide （IVCY） are effective for preserving renal function in adult pa-tients, CPA is a potent immunosuppressive agent thatinduces severe toxicity, including myelo- and gonadal toxicity, and increases the risk of secondary malig-nancy. Thus, treatment for controlling lupus nephritis activity, especially in children and adolescents, remains challenging. Cyclosporine A （CsA） and tacrolimus （Tac） are T-cell-specific calcineurin inhibitors that prevent the activation of helper T cells, thereby inhibiting thetranscription of the early activation genes of interleu-kin （IL）-2 and suppressing T cell-induced activation of tumor necrosis factor-α, IL-1β and IL-6. Therefore, both drugs, which we believe may be less cytotoxic, are attractive therapeutic options for young patients with lupus nephritis. Recently, a multidrug regimen of prednisolone （PDN）, Tac, and mycophenolate mofetile （MMF） has been found effective and relatively safe in adult lupus nephritis. Since the mechanisms of action of MMF and Tac are probably complementary, multidrug therapy for lupus nephritis may be useful. We propose as an alternative to IVCY, a multidrug therapy with mizoribine, which acts very similarly to MMF, and Tac, which has a different mode of action, combined with PDN for pediatric-onset lupus nephritis. We also believe that a multidrug therapy including CsA and Tac may bean attractive option for young patients with SLE and lupus nephritis展开更多
Lupus nephritis(LN),a severe manifestation of systemic lupus erythematosus,poses a substantial risk of progression to end-stage renal disease,with increased mortality.Conventional therapy for LN relies on broad-spectr...Lupus nephritis(LN),a severe manifestation of systemic lupus erythematosus,poses a substantial risk of progression to end-stage renal disease,with increased mortality.Conventional therapy for LN relies on broad-spectrum immunosuppressants such as glucocorticoids,mycophenolate mofetil,and calcineurin inhibitors.Although therapeutic regimens have evolved over the years,they have inherent limitations,including non-specific targeting,substantial adverse effects,high relapse rates,and prolonged maintenance and remission courses.These drawbacks underscore the need for targeted therapeutic strategies for LN.Recent advancements in our understanding of LN pathogenesis have led to the identification of novel therapeutic targets and the emergence of biological agents and small-molecule inhibitors with improved specificity and reduced toxicity.This review provides an overview of the current evidence on targeted therapies for LN,elucidates the biological mechanisms of responses and failure,highlights the challenges ahead,and outlines strategies for subsequent clinical trials and integrated immunomodulatory approaches.展开更多
Lupus nephritis leads to significant morbidity and mortality in patients with systemic lupus erythematous. Immunosuppressive agents are recommended in management of Class III, IV and V lupus nephritis. The goals of th...Lupus nephritis leads to significant morbidity and mortality in patients with systemic lupus erythematous. Immunosuppressive agents are recommended in management of Class III, IV and V lupus nephritis. The goals of therapy are to control the disease and to prevent relapse while minimizing side-effects of therapy. Most of the evidences in managements of Class III and IV lupus nephritis comes from randomized controlled trials using intravenous cyclophosphamides, oral mycophenolate mofetil and oral azathioprine. In Class V lupus nephritis, there are few studies available and they have assessed the use of intravenous cyclophsophamide, oral mycophenolates mofetil and oral cyclosporine. In this review article, we have summarized the major randomized controlled trials in managements of Class III, IV and V lupus nephritis and offer an interpretation of the evidence to date.展开更多
This study aimed to evaluate the efficacy and safety of mycophenolate mofetil(MMF)or tacrolimus(TAC)compared with azathioprine(AZA)as maintenance therapy for active lupus nephritis(ALN).Patients with ALN who responded...This study aimed to evaluate the efficacy and safety of mycophenolate mofetil(MMF)or tacrolimus(TAC)compared with azathioprine(AZA)as maintenance therapy for active lupus nephritis(ALN).Patients with ALN who responded to 24 weeks of induction treatment were enrolled.Patients who received MMF or TAC as induction therapy continued MMF or TAC treatment during the maintenance period,whereas those who received intravenous cyclophosphamide were subjected to AZA treatment.The primary endpoint was the incidence of renal relapse.Secondary endpoints included extrarenal flares and composite endpoints(deaths,end-stage renal disease,or doubling of serum creatinine levels).A total of 123 ALN patients(47 in the MMF group,37 in the TAC group,and 39 in the AZA group)were enrolled.The median follow-up time was 60 months.Ten MMF-treated patients,ten TAC-treated patients,and eight AZA-treated patients experienced renal relapses(P=0.844).The cumulative renal relapse rates in the MMF group(P=0.934)and TAC group(P=0.673)were similar to the renal relapse rate in the AZA group.No significant difference in the incidence of severe adverse event was observed among the groups.Long-term maintenance therapies with MMF or TAC might have similarly low rates of renal relapse and similar safety profiles compared with AZA.展开更多
文摘Recent advances in the management of lupus nephritis, together with earlier renal biopsy and selective use of aggressive immunosuppressive therapy, have contribut-ed to a favorable outcome in children and adolescents with systemic lupus erythematosus （SLE）. Neverthe-less, we believe that a more effective and less toxic treatment is needed to attain an optimal control of the activity of lupus nephritis. Recent published papers and our experiences regarding treatment of young patients with lupus nephritis using calcineurin inhibitors are re-viewed. Although it has been reported that intermittent monthly pulses of intravenous cyclophosphamide （IVCY） are effective for preserving renal function in adult pa-tients, CPA is a potent immunosuppressive agent thatinduces severe toxicity, including myelo- and gonadal toxicity, and increases the risk of secondary malig-nancy. Thus, treatment for controlling lupus nephritis activity, especially in children and adolescents, remains challenging. Cyclosporine A （CsA） and tacrolimus （Tac） are T-cell-specific calcineurin inhibitors that prevent the activation of helper T cells, thereby inhibiting thetranscription of the early activation genes of interleu-kin （IL）-2 and suppressing T cell-induced activation of tumor necrosis factor-α, IL-1β and IL-6. Therefore, both drugs, which we believe may be less cytotoxic, are attractive therapeutic options for young patients with lupus nephritis. Recently, a multidrug regimen of prednisolone （PDN）, Tac, and mycophenolate mofetile （MMF） has been found effective and relatively safe in adult lupus nephritis. Since the mechanisms of action of MMF and Tac are probably complementary, multidrug therapy for lupus nephritis may be useful. We propose as an alternative to IVCY, a multidrug therapy with mizoribine, which acts very similarly to MMF, and Tac, which has a different mode of action, combined with PDN for pediatric-onset lupus nephritis. We also believe that a multidrug therapy including CsA and Tac may bean attractive option for young patients with SLE and lupus nephritis
基金supported by grants from the National Natural Science Foundation of China(Nos.81970599 and 82170737)Key Laboratory of National Health Commission,and Key Laboratory of Nephrology,Guangdong Province,Guangzhou,China(Nos.2002B60118 and 2020B1212060028)Guangdong Medical Science and Technology Research Fund Project of China(No.A2020085)
文摘Lupus nephritis(LN),a severe manifestation of systemic lupus erythematosus,poses a substantial risk of progression to end-stage renal disease,with increased mortality.Conventional therapy for LN relies on broad-spectrum immunosuppressants such as glucocorticoids,mycophenolate mofetil,and calcineurin inhibitors.Although therapeutic regimens have evolved over the years,they have inherent limitations,including non-specific targeting,substantial adverse effects,high relapse rates,and prolonged maintenance and remission courses.These drawbacks underscore the need for targeted therapeutic strategies for LN.Recent advancements in our understanding of LN pathogenesis have led to the identification of novel therapeutic targets and the emergence of biological agents and small-molecule inhibitors with improved specificity and reduced toxicity.This review provides an overview of the current evidence on targeted therapies for LN,elucidates the biological mechanisms of responses and failure,highlights the challenges ahead,and outlines strategies for subsequent clinical trials and integrated immunomodulatory approaches.
文摘Lupus nephritis leads to significant morbidity and mortality in patients with systemic lupus erythematous. Immunosuppressive agents are recommended in management of Class III, IV and V lupus nephritis. The goals of therapy are to control the disease and to prevent relapse while minimizing side-effects of therapy. Most of the evidences in managements of Class III and IV lupus nephritis comes from randomized controlled trials using intravenous cyclophosphamides, oral mycophenolate mofetil and oral azathioprine. In Class V lupus nephritis, there are few studies available and they have assessed the use of intravenous cyclophsophamide, oral mycophenolates mofetil and oral cyclosporine. In this review article, we have summarized the major randomized controlled trials in managements of Class III, IV and V lupus nephritis and offer an interpretation of the evidence to date.
基金The present study was supported by the National Natural Science Foundation of China(No.81170671)Shanghai Health and Family Planning Committee Hundred Talents Program(No.2018BR37).
文摘This study aimed to evaluate the efficacy and safety of mycophenolate mofetil(MMF)or tacrolimus(TAC)compared with azathioprine(AZA)as maintenance therapy for active lupus nephritis(ALN).Patients with ALN who responded to 24 weeks of induction treatment were enrolled.Patients who received MMF or TAC as induction therapy continued MMF or TAC treatment during the maintenance period,whereas those who received intravenous cyclophosphamide were subjected to AZA treatment.The primary endpoint was the incidence of renal relapse.Secondary endpoints included extrarenal flares and composite endpoints(deaths,end-stage renal disease,or doubling of serum creatinine levels).A total of 123 ALN patients(47 in the MMF group,37 in the TAC group,and 39 in the AZA group)were enrolled.The median follow-up time was 60 months.Ten MMF-treated patients,ten TAC-treated patients,and eight AZA-treated patients experienced renal relapses(P=0.844).The cumulative renal relapse rates in the MMF group(P=0.934)and TAC group(P=0.673)were similar to the renal relapse rate in the AZA group.No significant difference in the incidence of severe adverse event was observed among the groups.Long-term maintenance therapies with MMF or TAC might have similarly low rates of renal relapse and similar safety profiles compared with AZA.
