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Treatment of lupus nephritis
1Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-1268, USA.
Abstract:
Patients with lupus nephritis pose a therapeutic challenge and stimulate investigation of innovative treatment strategies. Although patient survival and renal function outcomes have improved over the last 4 decades, contemporary immunosuppressive regimens are not consistently effective and often require extended courses associated with insidious toxicities. Several strategies are under investigation to induce remissions more rapidly and to reduce the risk of long courses of cytotoxic drug therapy. The combination of pulse methylprednisolone and pulse cyclophosphamide may be more effective than pulse cyclophosphamide alone for patients with relatively severe proliferative lupus nephritis. Ongoing clinical studies evaluate the risk/benefit of other intensive induction regimens (eg, combination fludarabine with relatively low-dose pulse cyclophosphamide). A particularly vigorous strategy employs immunoablative cyclophosphamide with or without stem cell rescue. Several studies of sequential immunosuppressive therapy are in progress. It is anticipated that long-term toxicities can be lessened by substituting various maintenance agents (eg, azathioprine or mycophenolate mofetil) after initial cyclophosphamide therapy has induced a renal response. Additional information is needed to determine the role of this strategy. Furthermore, a number of standard and experimental immunosuppressive regimens (that do not include cyclophosphamide) are under investigation as well. Innovative approaches (eg, costimulatory blockade) offer the hope of more effective treatments without the risks of contemporary regimens.
Insights
Innovative treatments for lupus nephritis aim for faster remission and reduced toxicity. Combining therapies like pulse methylprednisolone and cyclophosphamide shows promise, with ongoing research into novel strategies like costimulatory blockade.
Area of Science:
- Nephrology
- Immunology
- Rheumatology
Background:
- Lupus nephritis presents significant therapeutic challenges.
- Current immunosuppressive treatments have limitations in efficacy and toxicity.
- Improved patient survival and renal function have been observed, but better strategies are needed.
Purpose of the Study:
- To explore innovative treatment strategies for lupus nephritis.
- To identify methods for more rapid induction of remission.
- To reduce the need for long-term cytotoxic drug therapy.
Main Methods:
- Investigating combination therapies, such as pulse methylprednisolone and pulse cyclophosphamide.
- Evaluating intensive induction regimens, including fludarabine and cyclophosphamide combinations.
- Exploring immunoablative cyclophosphamide with or without stem cell rescue.
- Assessing sequential immunosuppressive therapy with maintenance agents like azathioprine or mycophenolate mofetil.
- Examining novel approaches such as costimulatory blockade.
Main Results:
- Combination therapy (pulse methylprednisolone and pulse cyclophosphamide) may be more effective for severe proliferative lupus nephritis than cyclophosphamide alone.
- Ongoing studies are evaluating risk/benefit profiles of various intensive induction regimens.
- Sequential therapy aims to reduce long-term toxicities by substituting maintenance agents after initial response.
Conclusions:
- Novel treatment strategies are under investigation to improve lupus nephritis outcomes.
- Combining therapies and sequential approaches hold potential for enhanced efficacy and reduced toxicity.
- Further research is needed to establish the role of these innovative strategies, including non-cyclophosphamide regimens and costimulatory blockade.