Efficacy of High-Dose Mycophenolate Mofetil in Multitarget Therapy for Lupus Nephritis: Two Consecutive Case Reports

Abstract

The complete remission rate for lupus nephritis (LN) is higher with multitarget therapy (MT) using tacrolimus (TAC), mycophenolate mofetil (MMF), and steroids than with steroid plus cyclophosphamide co-therapy. MT is also considered highly safe and is used to treat refractory LN. During MT, MMF is usually administered at a dose of 1 g/day similar to conventional MT; however, it remains unclear whether this is the optimal dose of MMF for Japanese patients, especially those refractories to conventional MT. We report two consecutive cases of refractory LN with conventional MT, case 1 was a 48-year-old woman with LN III (A) and nephrotic syndrome, and Case 2 was a 20-year-old man with LN IV-S (A), nephrotic syndrome, and acute kidney injury. LN was diagnosed by kidney biopsy. Because both these patients were refractory to conventional MT treatment (MMF at a dose of 1.0 g/day) for more than six months, MMF doses of 2.5 and 1.5-2.0 g/day were used as part of MT for cases 1 and 2, respectively. Increasing the MMF dose in MT to 1.5-2.5 g/day without increasing the steroid dose led to complete remission, without any recurrence, and allowed administration of a lower dose of a steroid such as prednisolone (5.5 ± 1.5 mg/day) 18 months after the MMF dose increase. The mean number of days from the start of the higher MMF dose of 1.5-2.5 g/day in MT to complete remission was 129.5 ± 10.5 days. Moreover, lymphopenia, hypogammaglobulinemia, gastrointestinal disturbances, or any infections were not observed as adverse events after increasing the MMF dose in MT. Thus, increasing MMF dose while maintaining the steroid dose in MT may induce complete remission; this will minimize the use of steroids in Japanese patients with refractory LN in conventional MT.

Keywords: induction therapy; lupus nephritis; multitarget therapy; mycophenolate mofetil; steroids; tacrolimus.

Figure 1. Case 1 data.

Time courses of proteinuria and eGFR (upper panel) and PSL, TAC, and MMF dosing (lower panel). eGFR: Estimated Glomerular Filtration Rate; MMF: Mycophenolate Mofetil; PSL: Prednisolone; TAC: Tacrolimus.

Figure 2. Case 2 data.

Time courses of proteinuria and eGFR (upper panel) and PSL, TAC, and MMF dosing (lower panel). eGFR: Estimated Glomerular Filtration Rate; MMF: Mycophenolate Mofetil; PSL: Prednisolone; TAC: Tacrolimus