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Lupus Nephritis

ACR Special Report: Philadelphia, PA, October 18-21, 2009

Lupus Nephritis

Lupus nephritis occurs in most patients with systemic lupus erythematous (SLE). The disease typically presents within the first two years after SLE diagnosis, with nearly half of all patients developing it in the first year.xviii Overall, an estimated 5 to 20 percent of patients, even those who receive appropriate treatment, develop end-stage renal disease requiring dialysis or transplant within 10 years of diagnosis.xix,xx,xxi Thus, identifying biomarkers that predict damage or nephritis flares as well as the best possible treatment to prevent long-term damage are critical research focuses in this area.

Some of the more relevant studies for people with lupus nephritis and the doctors who treat them include

  • Blood levels of mycophenolate mofetil (MMF): A study evaluating blood levels of MMF in patients with active and inactive lupus activity found a tenfold difference among patients in terms of the amount of the drug they received. This suggests that clinicians are not clear on exactly how much MMF is most beneficial.

    To determine the link between dosage and efficacy, French researchers measured blood levels of MMF in lupus nephritis patients and compared them to the level of disease in the patients. The higher the blood level (indicating a higher dosage), the more likely participants were to have inactive disease.

    Researchers identified a drug threshold of 35 mcg.h/ml as an appropriate target for MMF dosing to reduce the likelihood of disease activity. Their results also hinted that African-Americans, who tend to develop lupus nephritis earlier and have more severe lupus nephritis than Caucasians, may require even higher dosages.

    "The message for physicians," said presenter Laurent Arnaud, MD, during his presentation, "is to increase the MMF dosage as high as possible before encountering toxicities."xxii

    What this means for people with renal nephritis? If your doctor has had you on MMF for your disease and you continue to have active disease, the dosage may not be high enough. You should talk to your doctor about what is the best dosage for you.

  • Mycophenolate mofetil vs. azathioprine in maintenance therapy: The MAINTAIN (Mycophenolate Mofetil versus Azathioprine for Maintenance Therapy of Lupus Nephritis) trial compared MMF to azathioprine (AZA) for maintenance therapy in people with proliferative lupus nephritis.

    Bottom line? Both worked equally well with similar side effects, although those in the AZA group had slightly more blood-related side effects.xxiii "One major issue with MMF," noted the lead investigator Frédéric A. Houssiau, MD, PhD, of the Universite Catholique Louvain in Brussels, Belgium, "is that women who plan to become pregnant need to stop taking the therapy before they conceive given serious risks of birth defects."

    What this means for people with lupus? Either MMF or AZA is appropriate for preventing lupus nephritis flares. The decision on which drug to use depends on your individual situation.

  • Rituximab and lupus nephritis: Despite some small, uncontrolled clinical trials suggesting that rituximab (Rituxan®) may work for people with lupus nephritis, a study comparing its use in addition to MMF found no benefit overall.

    However, additional analysis of the results revealed that African-American patients were more likely to respond to rituximab than Caucasian patients. In addition, eight patients who received placebo had to be "rescued" with cyclophosphamide compared to just one patient who received rituximab.

    The study also showed that the rituximab participants had lower levels of anti-DNA antibodies and complement, indicators of disease activity, regardless of their response to the drug. What that means in terms of the disease itself, however, isn't clear.xxiv

    What this means for people with lupus? Rituximab may not have a place as therapy for lupus nephritis, although more studies in different populations are needed.


References

xviii Seshan SV, Jennette JC. Renal disease in systemic lupus erythematosus with emphasis on classification of lupus glomerulonephritis: advances and implications. Arch Pathol Lab Med. 2009;133(2):233-248.

xix Fiehn C, Hajjar Y, Mueller K, et al. Improved clinical outcome of lupus nephritis during the past decade: Importance of early diagnosis and treatment. Ann Rheum Dis. 2003;62(5):435-439.

xx Houssiau FA. Management of Lupus Nephritis: An Update. J Am Soc Nephrol. 2004;15(10):2694-2704.

xxi Lupus nephritis: prognostic factors and probability of maintaining life-supporting renal function 1 years after the diagnosis. Gruppo Italiano per lo Studio della Nefrite Lupica (GISNEL). Am J Kidney Dis. 1992;19(5):473-479.

xxii Arnaud L, Zahr N, Haroche J, et al. Low Mycophenolic Acid Area Under the Curve Is a Major Parameter of Systemic Lupus Erythematosus Activity. Presented at 73th Annual Scientific Meeting of the American College of Rheumatology, October 17-21, 2009; Philadelphia, PA.

xxiii Houssiau FA, D'Cruz DP, Sangle SR, et al. Azathioprine Versus Mycophenolate Mofetil for Maintenance Immunosuppression of Proliferative Lupus Nephritis: Results of a Randomized Trial (MAINTAIN); Presented at 73th Annual Scientific Meeting of the American College of Rheumatology, October 19, 2009; Philadelphia, PA.

xxiv Furie R, Looney RJ, Rovin B, et al. Efficacy and Safety of Rituximab in Subjects with Active Proliferative Lupus Nephritis (LN): Results From the Randomized, Double-Blind Phase III LUNAR Study. Presented at 73th Annual Scientific Meeting of the American College of Rheumatology, October 19, 2009; Philadelphia, PA.

 

More information about lupus and treatment advances can be found by visiting www.lupusresearch.org.

The 2009 American College of Rheumatology Meeting Special Report was made possible in part by generous support from Biogen Idec, Genentech and Johnson & Johnson.

Genentech Biogen IdecJohnson & Johnson

©2009 Alliance for Lupus Research. All Rights Reserved.

Contents herein may not be reproduced, republished or distributed without the prior written permission of the Alliance for Lupus Research. To request permission to reproduce, republish or distribute any part of this report, contact us at 212-218-2840 or email info@lupusresearch.org.

 


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