Blockade of Alternative Complement Pathway in Dense Deposit Disease

A patient aged 17 with dense deposit disease associated with complement activation, circulating C3 Nef, and Factor H mutation presented with nephrotic syndrome and hypertension. Steroid therapy, plasma exchange, and rituximab failed to improve proteinuria and hypertension despite a normalization of the circulating sC5b9 complex. Eculizumab, a monoclonal antibody directed against C5, was used to block the terminal product of the complement cascade. The dose was adapted to achieve a CH50 below 10%, but proteinuria and blood pressure were not improved after 3 months of treatment. 1. Introduction Dense deposit disease or DDD (formerly referred to as membranoproliferative glomerulonephritis type II) is a rare disease affecting less than 2 people per million, both adults and children. Nephrotic syndrome, severe hypertension, and progression to chronic renal failure are usually observed in patients with DDD. The histological pattern in light microcopy is limited to an enlargement of the mesangium with a mild mesangial cell hypercellularity [1]. Electron microscopy allows us to evidence electron-dense enlargement of the glomerular basement membrane that specially affects the lamina densa. Paradoxically, the precise composition of the dense deposits is not really known [2], while C3 fraction is only seen in the margin of the dense deposits but not within the dense deposits [1]. Complement activation with low C3 levels due to complement alternative pathway dysregulation is mostly due to the presence of a circulation C3 nephritic factor (C3 NeF) which is an autoantibody that stabilizes C3 convertase. In addition, mutations in the factor H gene have also been reported in a few patients [3]. Steroid therapy can be used but the efficacy was not proven. Specific treatment can be proposed like plasma exchanges. They is used to clear the C3 NeF and restore a normal complement balance. They have also shown encouraging results. New therapeutic approaches such as rituximab (anti-CD20) or eculizumab (anti-C5) could be proposed [1]. Eculizumab, a monoclonal antibody directed against complement C5 that blocks the final products of complement activation, might subsequently be considered as a relevant treatment in DDD. Here, we present the case of a patient presenting with DDD, in whom eculizumab was tried during 3 months. 2. Case Presentation The patient was a young man aged 17 and born from unrelated parents. In September 2007, at the age of 15, hypertension and nephrotic syndrome (proteinuria = 2.14？g/24？h, plasma albumin = 25？g/L) led to performing a renal biopsy and he was