Many nephrologists, myself included, are eager to find alternatives to cyclophosphamide in the management of lupus nephritis. As many of these patients are young men and women of child-bearing age, the effects of cyclophosphamide on fertility, along with bone marrow and other adverse effects make alternative medications more attractive. Several studies have suggested that mycophenolate mofetil (MMF) may be superior and less toxic than cyclophosphamide in the management of lupus nephritis. In the May issue of the Journal of the American Society of Nephrology, investigators report the result of a study comparing IV cyclophsphamide with oral MMF. While a reprint is not yet available for review, preliminary reports suggest that MMF is slightly more effective and less toxic in this trial. In a 24-week open-label induction study of 370 patients with class III-V lupus, there were no differences in the primary end-point (a prespecified decrease in urine protein/creatinine ratio and stabilization or improvement in serum creatinine) or the secondary end-point (complete renal remission, systemic disease activity and damage, and safety).  As well, there were no differences in the rate of adverse events between the 2 groups. For the studied patients, IV cyclophosphamide and oral MMF share similar efficacy and harm. This study adds to the growing evidence base showing no difference between these 2 treatment strategies.

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In the wake of the ONTARGET study, there is a movement away from using ACE and ARBs in combination for hypertension or general vascular protection. However, the combination is still an option for patients with heart failure where the it has been shown to reduce hospitalization. There remains a question whether the combination can reduce the rate of progression in diabetic nephropathy and other kidney diseases. While the ONTARGET study did include a relatetively small number of patients with nephropathy, it was not designed or powered to show a difference in renal outcomes. A new study, the VA-NEPHRON D, is currently underway to examine the effect of lisinopril plus losartan versus lisinopril plus placebo on the progression of chronic kidney disease. A copy of this study design can be found here. This study should shed light on the role of this medication combination in a disease state with a large unmet therapeutic need.

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