Long-Term Results of Triple Immunosuppression With Tacrolimus Added to Mycophenolate and Corticosteroids in the Treatment of Lupus Nephritis

Introduction: Addition of a calcineurin inhibitor (CNI) to corticosteroids and mycophenolate increased the renal response rate in lupus nephritis (LN) because of proteinuria reduction, but there is little long-term efficacy and safety data on this triple immunosuppressive regimen. Methods: This is a cohort study of patients with class III/IV/V LN whose proteinuria persisted despite initial standard therapy with mycophenolate mofetil (MMF) and prednisolone (PRED), in whom tacrolimus (TAC) was added (target 12-hour trough TAC plasma levels of 4-6 mu g/l). Results: A total of 22 patients with LN treated with triple immunosuppression were included, with follow-up of 61.1 +/- 28.1 months. Achieved trough levels of TAC and mycophenolic acid (MPA) were 3.8 to 5.7 mu g/l and 1.3 to 2.1 mg/l respectively. Significant proteinuria reduction occurred after 6 months and was sustained up to 5 years. Complete response (CR) and partial response (PR) rates at 12, 24, and 36 months was 59.1%, 72.7%, and 77.3% respectively. The slope of estimated glomerular filtration rate (eGFR) over time did not change after TAC was added. A total of 7 patients (31.8%) showed progressive chronic kidney disease (CKD). Two patients reached end-stage kidney disease during follow-up. Renal survival rate at -, 3, and 5 years was 100.0%, 95.0%, and 88.7% respectively. Two patients (9.1%) had renal relapse after 8.5 +/- 0.7 months. A total of 5 patients (22.7%) showed worsening of hypertension, and 3 (13.6%) had worsened hyperlipidemia. Other key adverse events included infection (n = 16, 1 in 7 patient-years) and gastrointestinal upset (n = 6). Conclusion: Triple immunosuppression with the addition of TAC to mycophenolate and PRED resulted in further proteinuria reduction and sustained disease quiescence in patients with LN whose proteinuria did not respond optimally to standard therapy.