Background: Mycophenolate mofetil (MMF) frequently is used as an alternative to intravenous cyclophosphamide to treat lupus nephritis. Whether MMF is adequate for patients with severely decreased kidney function at the time of treatment is uncertain.

Study design: We conducted a post hoc subgroup analysis of patients with low estimated glomerular filtration rates (eGFRs) from a large trial of MMF compared to cyclophosphamide in lupus nephritis.

Settings & participants: We included all patients with an eGFR <30 mL/min/1.73 m(2) from the Aspreva Lupus Management Study (ALMS).

Intervention: MMF (target, 3 g/d) compared to monthly intravenous cyclophosphamide (0.5-1 g/m(2)).

Outcomes: We compared the proportion of patients that responded to therapy and change in eGFR over 24 weeks.

Measurements: Response was evaluated by a decrease in proteinuria and stabilization or improvement of serum creatinine level.

Results: Of 370 patients in ALMS, 32 were included in the subgroup analysis: 20 randomly assigned to MMF and 12 randomly assigned to cyclophosphamide treatment. The patients included were similar at baseline between groups. Four (20.0%) patients treated with MMF responded compared with 2 (16.7%) patients treated with cyclophosphamide (risk ratio, 1.2; 95% CI, 0.3-5.1; P = 0.9). eGFR in the MMF group improved more quickly than in the cyclophosphamide group, by 1.51 (95% CI, 0.99-2.02) mL/min/1.73 m(2) each week (P < 0.001). Serious adverse events occurred in 9 (45.0%) MMF-treated patients and 7 (63.6%) cyclophosphamide-treated patients (P = 0.5).

Limitations: Small sample size and post hoc subgroup of a larger trial.

Conclusions: We did not detect a difference in the primary outcome of response in patients with low eGFR treated with MMF or cyclophosphamide. However, MMF may result in quicker recovery of kidney function compared with those treated with cyclophosphamide. Larger studies including more patients with poor kidney function are warranted.