Grootscholten C et al. (2006) Azathioprine/methylprednisolone versus cyclophosphamide in proliferative lupus nephritis. A randomized controlled trial. Kidney Int 70: 732–742

There is currently no consensus as to whether cyclophosphamide is better than azathioprine, in combination with corticosteroids, for the treatment of proliferative lupus nephritis—although azathioprine has less gonadal toxicity.

In this open-label trial, 87 patients with proliferative lupus nephritis were randomly allocated to 2 years of treatment with either intravenous pulsed cyclophosphamide (750 mg/m2, 13 pulses) plus oral prednisone, or to oral azathioprine (2 mg/kg daily) plus intravenous pulsed methylprednisolone (3 × 3 pulses of 1 g) and oral prednisone. The 2-year incidence of partial or complete renal remission was similar in both groups. After a median follow-up of 5.7 years, however, doubling of initial serum creatinine level occurred more frequently in azathioprine-treated than in cyclophosphamide-treated patients (although the difference was not statistically significant), and relapses occurred more often in azathioprine-treated patients, which indicated that cyclophosphamide had greater efficacy than azathioprine. There were also more infections (mostly herpes zoster) in azathioprine-treated than in cyclophosphamide-treated patients; the authors attribute this finding to the higher corticosteroid doses given with azathioprine. Indicators of ovarian function were similar in both groups, but the four women who developed premature ovarian failure had all received cyclophosphamide. After a median follow-up of 6.3 years, 88.4% of the azathioprine-treated patients had not required cyclophosphamide treatment, which consequently improved their prognosis, in terms of fertility.

Longer follow-up is needed before final conclusions can be drawn in relation to the effects of these two regimes on renal function.