State-of-the-Art Approaches to Rheumatic Disease Diagnosis, Management & Treatment

Treatment of Lupus Nephritis

Gerald Appel, MD, director of the Center for Glomerular Diseases at Columbia University College of Physicians and Surgeons, New York, discussed how he treats lupus nephritis. He began by describing what he looks for in the biopsy of a patient with lupus nephritis and emphasized the importance of reading the pathology report. He highlighted five important pieces of information to glean from the report:

First, to allow for an accurate interpretation, the biopsy must have at least seven glomeruli and, ideally, 20–25 glomeruli. The next important information is the Inter­national Society of Nephrology (ISN) class. Dr. Appel only gives “vigorous treatment” to patients with Class III + V or Class IV + V lupus nephritis. Additionally, he focuses treatment on patients with active or active and chronic lupus nephritis. He explained that he typically does not treat patients who have only chronic lupus nephritis because the more chronicity in the biopsy, the less likely the patient will benefit from treatment. This factor is especially the case for patients with interstitial fibrosis. He then explained the importance of determining if the deposits are extensive, especially as visualized by electron microscope. Finally, he emphasized that fibrinoid necrosis of glomerular caps and an abundance of crescents, while bad, is treatable.

Dr. Appel then introduced the Kidney Disease Improving Global Outcomes (KDIGO) Treatment Guideline and explained that patients with serious lupus nephritis should be treated with mycophenolate mofetil and steroids or cyclophosphamide plus steroids. The guideline, which is supported by several clinical trials that combine expertise in rheumatology and nephrology, includes a flowchart that describes these two different regimens.

Dr. Appel also reviewed the relevant clinical trials for this treatment approach, beginning with a 2005 multi-center trial published in the New England Journal of Medicine that compared mycophenolate mofetil to intravenous cyclophosphamide as an induction therapy for severe lupus nephritis.¹⁰ Although Dr. Appel acknowledged the many flaws in the trial, the study found patients treated with mycophenolate mofetil had better outcomes than those treated with cyclophosphamide.

The second relevant clinical trial was the Aspreva Lupus Management Study (ALMS) trial, during which a blinded clinical endpoint committee judged patient response based on a decrease of proteinuria by less than 3 g if baseline nephrotic or by greater than 50% in patients with sub­nephrotic proteinuria.¹¹ The committee also judged response based on the stabilization—or improvement—of serum creatinine levels. The ALMS trial revealed no significant difference between mycophenolate mofetil and intravenous cyclophosphamide.

Finally, the Euro-Lupus Nephritis Trial was a multi-center, prospective trial of 90 patients with proliferative lupus nephritis.¹² The study included an initial follow-up of 41 months and subsequent 10-year follow-up. Patients received monthly high doses of intravenous cyclophosphamide or low doses of intravenous cyclophos­phamide. The Euro-Lupus Nephritis Trial documented identical outcomes in the two groups.

The results from all three clinical trials suggest it may be possible to treat patients with lupus nephritis without using cyclophosphamide. This alternative is worth considering because cyclophosphamide is associated with multiple side effects. Dr. Appel concluded the most important thing is individualized therapy, saying, “You have a lot more choices than you had a few years ago.”