Background Multi-target therapy using two immunosuppressive drugs with different mechanism of action such as mycophenolate mofetil and tacrolimus (Tac) for lupus nephritis (LN) 1 seems to be a promising treatment strategy. On the other hand, we reported a case of LN with class IV plus V unresponsive to cyclophosphamide (CY), which was successfully treated with the addition of Tac 2.
Objectives To assess the effectiveness of combination therapy with CY and Tac for class III and IV (or III/IV plus V) LN as a remission induction therapy and to discuss the potentiality of this multi-target therapy by reference to renal pathological findings.
Methods We evaluated 13 patients with active LN who received renal biopsy at Saitama Medical Center between January 2007 and December 2012. The complete renal remission was defined as the spot urine protein/creatinine ratio <0.5g/gCr or urine protein (±)/(−) values in urinalysis and normal eGFR or improvement of eGFR according to the EULAR/ERA-EDTA recommendation. Renal pathological findings were assessed according to the 2003 ISN/RPS classification for LN. Activity and chronicity were evaluated by NIH semiquantitative histologic scoring system.
Results All cases were class IV. Six cases had membranous nephropathy (Class IV + V). CY was initiated as a remission induction therapy with 500mg/biweekly for three months (the Euro-Lupus protocol). Starting dose of prednisolone (PSL) was 1mg/kg/day. Methylprednisolone pulse therapy was not used to avoid the increase of cumulative steroids dose. Seven out of 13 cases received multi-target therapy with Tac (CY + Tac group). In the other 6 cases, Tac (n=1) or azathioprine (n=4) was prescribed as a maintenance therapy after CY (CY-IS group). The average of cumulative steroids at 6 months was 4093.3mg in CY + Tac group and 3644.8mg in CY-IS group (p=0.84). The average of daily oral PSL at 6 months was 13.0mg in CY + Tac group and 12.5mg in CY-IS group (p=0.63). The complete remission rate at 12 months was 85.7% in CY + Tac group and 66.7% in CY-IS group (p=0.41). Although chronicity was observed more commonly in CY + Tac group (p=0.032), the remission rate in patients with chronicity was 85.7% in CY + Tac group and 33.3% in CY-IS group (p=0.097). In CY + Tac group, side effects including infections were not increased as compared to CY-IS group. Although transient increase of serum creatinine was observed in two cases in CY + Tac group, renal function recovered after the dose reduction of Tac.
Conclusions This retrospective study shows that multi-target therapy such as the Euro-Lupus protocol plus Tac may be effective for refractory LN with chronicity in renal pathological findings. Prospective cohort studies should be conducted to detect the efficacy and safety of multi-target therapy for active and chronic LN in the future.
Bao H, Liu Z-H, Xie H-L, Hu W-X, Zhang H-T, Li L-S. Successful treatment of class V+IV lupus nephritis with multitarget therapy. J Am Soc Nephrol 2008;19(10):2001-10.
Kurasawa T, Nagasawa H, Nishi E, Takei H, Okuyama A, Kondo T, et al. Successful treatment of class IV+V lupus nephritis with combination therapy of high-dose corticosteroids, tacrolimus and intravenous cyclophosphamide. Intern Med 2013;52(10):1125-30.
Disclosure of Interest R. Sakai: None declared, A. Shibata: None declared, K. Chino: None declared, A. Okuyama: None declared, T. Kondo: None declared, E. Nishi: None declared, H. Takei: None declared, H. Nagasawa: None declared, K. Amano Grant/research support: Astellas Pharma Inc. and Chugai Pharmaceutical Co., Ltd.