Tacrolimus Monotherapy after Intravenous Methylprednisolone in Adults with Minimal Change Nephrotic Syndrome

Abstract

Glucocorticoid treatment is the first choice therapy for adults with minimal change nephrotic syndrome; however, this therapy associates with many adverse effects. Tacrolimus may be an alternative to conventional glucocorticoid therapy. To investigate this possibility, we conducted a prospective, randomized, controlled trial (WHO International Clinical Trials Registry Platform: ChiCTR-TRC-11001454) in eight renal units across China. We randomized enrolled patients with adult-onset minimal change nephrotic syndrome (n=119) to receive glucocorticoid therapy or tacrolimus after intravenous methylprednisolone (0.8 mg/kg per day) for 10 days. Patients received a conventional glucocorticoid regimen or tacrolimus monotherapy, starting with 0.05 mg/kg per day (target trough whole-blood level of 4-8 ng/ml) for 16-20 weeks and subsequently tapering over approximately 18 weeks. Remission occurred in 51 of 53 (96.2%; all complete remission) glucocorticoid-treated patients and 55 of 56 (98.3%; 52 complete and three partial remission) tacrolimus-treated patients (P=0.61 for remission; P=0.68 for complete remission). The groups had similar mean time to remission (P=0.55). Relapse occurred in 49.0% and 45.5% of the glucocorticoid- and tacrolimus-treated patients, respectively (P=0.71), with similar time to relapse (P=0.86). Seven (13.7%) glucocorticoid-treated and four (7.3%) tacrolimus-treated patients suffered frequent relapse (P=0.28); five glucocorticoid-treated and two tacrolimus-treated patients became drug dependent (P=0.26). Adverse events occurred more frequently in the glucocorticoid group (128 versus 81 in the tacrolimus group). Seven adverse events in the glucocorticoid group and two adverse events in the tacrolimus group were serious. Consequently, tacrolimus monotherapy after short-term intravenous methylprednisolone is noninferior to conventional glucocorticoid treatment for adult-onset minimal change nephrotic syndrome in this cohort.

Keywords: adults; clinical trial; minimal change nephrotic syndrome; monotherapy; tacrolimus.

Figure 1.

Flow chart of study populations, including the number of patients who were assessed for eligibility, underwent randomization, and completed the study treatment. Of 162 patients assessed for eligibility, 43 patients were withdrawn, 119 patients were randomly enrolled in GC group (n=56) or TAC group (n=63). One hundred patients (47 in the GC and 53 in the TAC group) completed at least 24 weeks of therapy.

Figure 2.

Percentage of patients who achieved complete remission (CR) and partial remission (PR) during the 36 weeks of therapy. The treatment efficacy was evaluated on the basis of the outcome of patients who completed at least 12 weeks of therapy. The remission rate was 96.2% (51 out of 53 patients) and 98.3% (55 out of 56 patients) in the GC and TAC group, respectively (P=0.61). Complete remission was experienced by 51 out of 53 patients (96.2%) in the GC group and 52 out of 56 patients (92.9%) in the TAC group (P=0.68). Three patients (2 in the GC group and 1 in the TAC group) showed no remission. G, GC group; T, TAC group.

Figure 3.

Changes in proteinuria and serum albumin levels at baseline and during the 36 weeks of therapy. (A) Proteinuria and (B) serum albumin before therapy (week 0) and during the 36 weeks of therapy. No significant differences between the two groups were observed in mean proteinuria and serum albumin levels before therapy and during the 36 weeks of therapy (P>0.05).

Figure 4.

The incidence of the first relapse in the GC and TAC groups. Kaplan-Meier curves show the probability of the event (first relapse) at different time points between the GC and TAC groups (P=0.81 by long rank test). Point 0 represents onset of remission.

Figure 5.

Changes in SCr and eGFR levels at baseline, during the periods of therapy and follow-up. SCr (A) and eGFR (B) before therapy (week 0), during the periods of therapy and follow-up. The SCr and eGFR levels before therapy, during the periods of therapy and follow-up did not differ significantly between the GC and TAC groups (P>0.05).