The long awaited ALMS study was recently published in JASN. This was one of the largest studies ever done in patients with glomerulonephritis. Previous data suggested a possible benefit of mycophenolate mofetil (MMF) over standard regimens of intravenous cyclophosphamide (IVC) for up front treatment of lupus nephritis. These trials were rather homogenous in terms of racial/ethnic background and included mostly patients without severe acute lupus nephritis associated with renal insufficiency. The ALMS study attempted to address these deficiencies by enrolling a more balanced representation of races and ~70% of patients with WHO IV nephritis. Patients received escalating doses of MMF (goal of 3 gm/d by week 3) or NIH-based regimen of monthly IVC. All patients received a tapering dose of oral prednisone. Intravenous pulses of methylprednisolone were not part of the regimen. Almost 9% of total patients had eGFR < 30 ml/min. Induction treatment was continued over 6 months. Results from a randomized maintenance phase of the study will also be published sometime in 2010. The primary end point was a prespecified decrease in urine protein/creatinine ratio and stabilization or improvement in serum creatinine. Secondary end points included complete renal remission, systemic disease activity and damage, and safety. Although there was a slightly higher response rate with MMF (56.2% vs 53%), the result was not statistically significant. Secondary endpoints were also similar, and overall rates of adverse events and infections were similar. However, among black, mixed race and Hispanic patients, the response rate was significantly higher for the MMF arm. Interestingly, Asians and whites had a higher mean average dose compared to blacks. There was no difference in response rate according to biopsy class (WHO 3 vs 4 vs 5 or combination). Response rates were similar for MMF and IVC in the patients with eGFR < 30 ml/min. Long term data will be very interesting in terms of comparing renal survival, relapse rates and effects of female reproduction. One also wonders if a more aggressive approach of higher dose MMF up front rather than titration over 3 weeks at induction would have resulted in higher remission rates or more intolerance due to GI side effects. Although analysis of long term follow up data will be valuable, it appears that MMF is an acceptable alternative to IVIC for most patients with lupus nephritis and may even be superior in non-white, non-Asian populations. Benjamin J Freda, DO

In this communication, the authors report the results (by intent-to-treat) of the multinational, randomized controlled trial of IV cyclophosphamide (n=185) and oral mycophenolate mofetil (MMF, n=185) for the induction treatment phase of lupus nephritis classes III-V (n=370). The primary end-point was a pre-specified decrease in protein to creatinine ratio (to < 3 in patients with a ratio =3 or by 50% if ratio <3) and stabilization or improvement of serum creatinine values at 24 weeks. The hypothesis was that MMF will be superior to IV cyclophosphamide in the induction of response as defined. Other end-points were complete renal remission, disease activity, damage, and safety. Race/ethnicity and place were adjusted for in the analyses. MMF was not superior to IV cyclophosphamide in achieving either the primary or the secondary end-points of the trial. However, there were some differences in the response rates with more patients in the high risk group (non-Caucasian groups) responding to MMF than to IV cyclophosphamide. The authors postulate that since medical and socioeconomic factors were controlled for in this study (to a certain extent), the difference observed in the response rates between high and low risk groups may be more directly related to other race-ethnic associated factors. Graciela S. Alarcon, MD