Tacrolimus is an alternative therapeutic option for the treatment of refractory lupus nephritis

Abstract

We conducted an open-labeled, prospective study to determine the efficacy and safety of tacrolimus as an alternative therapeutic option for those patients with refractory lupus nephritis. The study population comprised one male and eight female patients with diffuse proliferative lupus nephritis. All patients had failed to respond to sufficient intravenous cyclophosphamide therapy with proteinuria of >or=1 g/day and active urinary sediments. Tacrolimus (0.1 mg/kg/day) was administered for 1 year with adjusting drug level (4-10 microg/l). The mean serum creatinine level and spot urine protein creatinine ratio (UPCR) at baseline were 1.39 mg/dl and 2.27, respectively. After the treatment, proteinuria reduced significantly from median UPCR value of 2.19 (range, 1.19-3.34) to 0.44 (range, 0.12-2.13) (p < 0.05). Seven (78%) of the nine patients showed a complete clinical response, which was defined as stabilization in the disease-activity markers and serum creatinine level with reduction of >or=50% in UPCR; two patients showed complete remission with UPCR <0.2. One patient showed treatment failure because of the disease progression. No serious adverse effects were observed during the study. This study demonstrates that tacrolimus can show a significant therapeutic response in cases that are refractory to the standard regimen for diffuse proliferative lupus nephritis.

Long-Term Tacrolimus-Based Immunosuppressive Treatment for Young Patients with Lupus Nephritis: A Prospective Study in Daily Clinical Practice

“…Several papers have reported the efficacy and absence of serious adverse effects of Tac plus PDN when administered as induction and maintenance therapy for patients with proliferative and membranous LN [7,12,13,14,15,16,17,18,19,20]. Each of these studies described the need for aggressive cytotoxic therapy to induce remission of LN; however, long-term cytotoxic therapy can have serious side effects.…”

“…Each of these studies described the need for aggressive cytotoxic therapy to induce remission of LN; however, long-term cytotoxic therapy can have serious side effects. In this context, Tac has been reported to be an alternative treatment option to IVCY or MMF for patients with LN, although calcineurin inhibitor-related nephrotoxicity remains a major concern [7,12,13,14,15,16,17,18,19,20]. Recently, Chen et al [19] reported the short-term efficacy and safety of Tac compared with IVCY for induction therapy in patients with active LN (ISN/RPS class III, IV and V).…”

“…Therefore, we hypothesized that calcineurin inhibitors might be feasible and less cytotoxic alternatives to CY for maintenance treatment, and possibly induction treatment, in young patients with LN [17,18,21]. However, our current knowledge of the efficacy and safety of CsA or Tac treatment is based on relatively short-term studies of up to 12 months [10,11,12,13,14,15,16,19,20]. Moreover, little is known of the long-term efficacy and safety of Tac-based immunosuppressive treatment in young patients with LN in daily clinical practice [17,18].…”

“…Cyclosporine A (CsA) and tacrolimus (Tac) are T cell-specific calcineurin inhibitors that prevent activation of helper T cells, thereby inhibiting the transcription of interleukin (IL)-2 and proinflammatory cytokines such as tumor necrosis factor-α, IL-1β, and IL-6 [7,8]. Recently, CsA and Tac combined with prednisolone (PDN) have been observed to be useful to treat difficult cases of LN, including pediatric-onset cases [7,9,10,11,12,13,14,15,16,17,18,19,20]. These studies found that both CsA and Tac ameliorated the clinical activity of lupus and exerted an anti-proteinuric effect in LN.…”

Lupus Nephritis

“…A significant reduction of proteinuria was observed at 3 months and 12 (70%) patients achieved clinical response after a 2-year follow-up. In a pilot study, Mok et al demonstrated the safety and efficacy of tacrolimus when used (39). Tacrolimus (0.1 mg/kg per day) was administered for 1 year.…”