NDT Advance Access originally published online on January 23, 2006
Nephrology Dialysis Transplantation 2006 21(6):1742-1743; doi:10.1093/ndt/gfk068
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Rituximab-induced long-term remission of membranous lupus nephritis
Email: iva.gunnarsson{at}karolinska.seSir,
Rituximab is a chimeric anti-CD20 monoclonal antibody that has proved to be effective in depleting B-lymphocytes in vivo [1]. We report here a case of a woman with severe membranous lupus nephritis who was treated with rituximab with significant and persistent improvement during a 3 year follow-up. She had previously failed to respond to therapy with cyclophosphamide, prednisolone, cyclosporine and mycophenolate mofetil (MMF).
A 16-year-old female with SLE and nephrotic syndrome had a renal biopsy performed showing membranous lupus nephritis (WHO class V). The patient was treated with prednisolone continuously and a sustained remission of the nephrotic syndrome was achieved. At the age of 22, the patient had a relapse and a new renal biopsy showed WHO class V. The prednisolone dose was increased and i.v. cyclophosphamide was administered monthly for 6 months. A re-biopsy showed persistent WHO class V. Cyclophosphamide i.v. pulse therapy was continued but due to incomplete effect and side effects, therapy was stopped after two infusions. The patient was started on oral cyclosporine, 24-h urine albumin was 5.2 g and glomerular filtration rate (GFR) was 59 ml/min. During treatment, proteinuria decreased to approximately 1–2 g/24 h.
At –27 months (before start of rituximab) the then 25-year-old woman was treated with cyclosporine 75 mg and prednisolone 5 mg/day (Table 1). At –12 months, the nephrotic syndrome relapsed and the dose of cyclosporine was increased to 150 mg, prednisolone to 30 mg and MMF 1g/day was added, subsequently increased to 2 g/day. A year later (–1 month), the patient developed pneumonia with septicaemia and a severe nephrotic syndrome with extensive oedema, pericardial effusion and hypertension developed. GFR was 5 ml/min. Cyclosporine and MMF were withdrawn and the patient was given high doses of i.v. methylprednisolone. Kidney biopsy showed lupus nephritis WHO class Vb and vasculopathy with thrombotic microangiopathy and signs of malignant hypertension. At that time (month 0), i.v. rituximab (Mabthera) 375 mg/m2 body surface area was given once weekly for 4 weeks in combination with i.v. cyclophosphamide 0.5 g/m2 twice. After treatment, the CD19 positive B-lymphocytes were totally depleted, starting to recover after approximately 1 year. By then, the ongoing low-dose prednisolone treatment was combined with MMF in a dose of 0.5 g/day. 24 months after treatment with rituximab, GFR had increased to 40 ml/min. At 36 months, treatment consisted of prednisolone 5 mg in combination with MMF 1g/day and antihypertensive drugs. Serum creatinine was 118 µmol/l, serum albumin 36 g/l and 24-h urine albumin 7 mg (Table 1).
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In membranous lupus nephritis the optimal treatment is controversial although remission of the nephrotic syndrome can occur following the treatment with steroids in combination with cyclophosphamide, cyclosporine or MMF. Despite extensive immunosuppressive treatment during the disease course, the nephrotic syndrome persisted in our patient and was further complicated by infectious complications and renal failure. At that time rituximab was given in combination with two infusions of cyclophosphamide with long-standing beneficial results. Rituximab-induced remission of refractory nephrotic syndrome has previously been reported in patients with idiopathic membranous nephropathy and membranous lupus nephritis [2,3] and promising effects of rituximab in short-term follow-ups in lupus nephritis patients have been described [4,5]. This strengthens the view that depletion of B-cells with rituximab may be a new therapeutic option in patients with severe therapy-resistant membranous lupus nephritis.
Conflict of interest statement. None declared.
1 Department of Nephrology Danderyd Hospital2 Department of Rheumatology Karolinska University Hospital Stockholm Sweden
References
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- Ruggenenti P, Chiurchiu C, Brusegan V et al. Rituximab in idiopathic membranous nephropathy: an one-year prospective study. J Am Soc Nephrol 2003; 14: 1851–1857
[Abstract/Free Full Text] - Fra GP, Avanzi GC, Bartoli E. Remission of refractory lupus nephritis with a protocol including rituximab. Lupus 2003; 12: 783–787
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[Abstract/Free Full Text] - van Vollenhoven RF, Gunnarsson I, Welin-Henriksson E et al. Biopsy-verified response of severe lupus nephritis to treatment with rituximab (anti-CD20 monoclonal antibody) plus cyclophosphamide after biopsy documented failure to respond to cyclophosphamide alone. Scand J Rheumatol 2004; 33: 423–427[CrossRef][Web of Science][Medline]
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