Severe Lupus Nephritis

Abstract

Objective: The renal prognosis of active proliferative lupus nephritis（LN）（ISN/RPS Class III or IV）has been improved by introducing intravenous cyclophosphamide pulse therapy（IVCY）or mycophenolate mofetil（MMF）. However, there are still a certain number of refractory patients who progressed to end stage renal disease. We examined risk factors for poor renal prognosis and the current status of novel treatment strategies.

Results: Risk factors for poor renal prognosis have been reported from several institutions in Japan using their registries. We identified higher level of serum creatinine at renal biopsy, combination of proliferative lesions and membrane lesions（mixed type）, and combination of acute lesions and chronic lesions（A/C）, as independent risk factors for poor renal prognosis. In order to improve renal prognosis, it is important to induce remission using potent initial therapy. Various clinical trials of biologics, using MMF or IVCY as a standard therapy, have been conducted. However, no biologics have surpassed the standard therapy to date. On the other hand, an increasing number of reports demonstrated the efficacy of combination therapy with MMF and calcineurin inhibitors, named multi-target therapy. We also have used this regimen for severe LN and showed high remission rate and persistent remission.

Conclusion: Although the multi-target therapy seems to be effective, it is necessary to examine its long-term efficacy and safety. In addition, clinical trials of biologics targeted to B cells for active LN are still being conducted. We hope new treatment options will become available in the near future.