Unexpected effect of ANTI-TNF therapy in Membranous Glomerulonephritis

Introduction and Aims: Membranous glomerulonephritis, the most common cause of nephrotic syndrome in adults, is an autoimmune disorder in which the M-type phospholipase A2 receptor (PLA2R), was recently identified as the autoantigen. Psoriasis is an immune-mediated chronic inflammatory skin disease with a strong genetic background. Few cases of association of these two disorders were reported. We report a case of idiopathic membranous glomerulonephritis in a psoriatic patient who responded to treatment with infliximab. Case Report: In March 2011 a 43-year-old woman with a history of psoriasis vulgaris, without evidence of psoriatic arthropathy, was admitted to hospital for nephrotic syndrome with history of proteinuria (3gr/day) started six months before. Blood pressure was 110/70 mmHg. The laboratory test showed creatinine clearance of 211 ml/min, urea 22 mg/dl, total protein 5.7 g/dl, albumina 2.34 g/dl ,total cholesterol 216 mg/dl, LDL-cholesterol 114 mg/dl, and 24- hours proteinuria 6.7 g. Serological test for hepatitis B and C were negative. Test for ANA, ENA, ANTI-DNA were all negative. Renal biopsy revealed membranous glomerulonephritis. In May 2011 she started therapy with Adalimumab (40 mg every 15 days) for psoriasis. We decided to delay therapy for nephrotic syndrome, because of this contemporary treatment. At that time 24-hours proteinuria was 5,7 g. She was not on drugs acting on renin-angiotensin system because of low blood pressure. Therapy with Adalimumab resulted in disappearance of psoriatic skin lesions with an unexpected progressive reduction of 24-hours proteinuria: (July 2011: 1.215 g/day and September 0,240 gr/day). Conclusions: Although the primary mechanism in the pathogenesis of proteinuria in membranous nephropaty is considered in-situ formation of glomerular immune deposits, a contributory role of cellular immunity is also implied. TNF a is a pro-inflammatory cytokine produced in response to various stimuli not only by monocytes and macrophages but also by glomerular and mesangial cells: it may play a pathogenetic role in the induction or maintenance of glomerular barrier dysfunction. This is the first report of therapeutic efficacy of adalimumab in membranous glomerulonephritis.