Comparison of the Efficacy and Safety of Tacrolimus and Low-Dose Corticosteroid with High-Dose Corticosteroid for Minimal Change Nephrotic Syndrome in Adults.

BACKGROUND: Tacrolimus is used as a steroid-sparing immunosuppressant in adults with minimal change nephrotic syndrome. However, combined treatment with tacrolimus and low-dose steroid has not been compared with high-dose steroid for induction of clinical remission in a large-scale randomized study.

METHODS: In this 24-week open-label noninferiority study, we randomized 144 adults with minimal change nephrotic syndrome to receive 0.05 mg/kg twice-daily tacrolimus plus once-daily 0.5 mg/kg prednisolone, or once-daily 1 mg/kg prednisolone alone, for up to 8 weeks or until achieving complete remission. Two weeks after complete remission, we tapered the steroid to a maintenance dose of 5-7.5 mg/d in both groups until 24 weeks after study drug initiation. The primary end point was complete remission within 8 weeks (urine protein: creatinine ratio <0.2 g/g). Secondary end points included time until remission and relapse rates (proteinuria and urine protein: creatinine ratio >3.0 g/g) after complete remission to within 24 weeks of study drug initiation.

RESULTS: Complete remission within 8 weeks occurred in 53 of 67 patients (79.1%) receiving tacrolimus and low-dose steroid and 53 of 69 patients (76.8%) receiving high-dose steroid; this difference demonstrated noninferiority, with an upper confidence limit below the predefined threshold (20%) in both intent-to-treat (11.6%) and per-protocol (17.0%) analyses. Groups did not significantly differ in time until remission. Significantly fewer patients relapsed on maintenance tacrolimus (3-8 ng/ml) plus tapered steroid versus tapered steroid alone (5.7% versus 22.6%, respectively; P =0.01). There were no clinically relevant safety differences.

CONCLUSIONS: Combined tacrolimus and low-dose steroid was noninferior to high-dose steroid for complete remission induction in adults with minimal change nephrotic syndrome. Relapse rates were significantly lower with maintenance tacrolimus and steroid compared with steroid alone. No clinically-relevant differences in safety findings were observed.