Successful treatment of class V+IV lupus nephritis with multitarget therapy

Abstract

Treatment of class V+IV lupus nephritis remains unsatisfactory despite the progress made in the treatment of diffuse proliferative lupus nephritis. In this prospective study, 40 patients with class V+IV lupus nephritis were randomly assigned to induction therapy with mycophenolate mofetil, tacrolimus, and steroids (multitarget therapy) or intravenous cyclophosphamide (IVCY). Patients were treated for 6 mo unless complete remission was not achieved, in which case treatment was extended to 9 mo. An intention-to-treat analysis revealed a higher rate of complete remission with multitarget therapy at both 6 and 9 mo (50 and 65%, respectively) than with IVCY (5 and 15%, respectively). At 6 mo, eight (40%) patients in each group experienced partial remission, and at 9 mo, six (30%) patients receiving multitarget therapy and eight (40%) patients receiving IVCY experienced partial remission. There were no deaths during this study. Most adverse events were less frequent in the multitarget therapy group. Calcineurin inhibitor nephrotoxicity was not observed, but three patients developed new-onset hypertension with multitarget therapy. In conclusion, multitarget therapy is superior to IVCY for inducing complete remission of class V+IV lupus nephritis and is well tolerated.

Trial registration: ClinicalTrials.gov NCT00298506.

Figure 1.

Enrollment of patients, treatment assignments, and outcomes according to the intention-to-treat analysis. ^aCR <6 mo, patients achieved complete remission within 6 mo; CR 6∼9 mo, patients achieved complete remission between 6 and 9 mo; Not CR, patients did not achieve complete remission within 9 mo.

Figure 2.

Remission rates in the multitarget therapy and IVCY groups after 6 and 9 mo (intention-to-treat). *P < 0.05 versus the multitarget therapy group.

Figure 3.

Probability of achieving complete remission for patients treated with multitarget therapy or IVCY. P < 0.05 compared between the two groups.

Figure 4.

Change of urine protein (mean ± SD, g/24 h) from the baseline value at each follow-up evaluation in patients treated with multitarget therapy or IVCY. *P < 0.05 versus baseline value.

Figure 5.

Change of serum albumin (mean ± SD, g/L) from the baseline value at each follow-up evaluation in patients treated with multitarget therapy or IVCY. *P < 0.05 versus baseline value.

Figure 6.

Change of urine RBC (median, ×10⁴/ml) from the baseline value at each follow-up evaluation in patients treated with multitarget therapy or IVCY. *P < 0.05 versus baseline value.

Figure 7.

Histologic response in a patient who achieved complete remission after the induction therapy. Representative lesions in a patient who achieved complete remission before (A through C) and after (D through F) treatment are shown. (A) Glomerulus with global endocapillary proliferation, leukocyte influx, crescent formation, and disruption of Bowman's capsule (periodic acid-Schiff). (B) Glomerulus bearing subendothelial, subepithelial, and mesangial fuchsinophilic deposits (Masson's trichrome). (C) Glomerulus with electron-dense deposits on the epithelial surface of the glomerular basement membrane. (D) Glomerulus with extra- and endocapillary proliferation alleviated and some tuft adhesions forming after the therapy (periodic acid-Schiff). (E) Glomeruli with fuchsinophilic deposits decreased significantly after the therapy (Masson's trichrome). (F) Glomerulus with electron-dense deposits surrounded by and incorporated into the glomerular basement membrane in the posttreatment biopsy. Magnifications: ×400 in A and D; ×1000 in B and E; ×20,000 in C and F.