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New Approaches to the Treatment of Dense Deposit Disease
Journal article   Open access

New Approaches to the Treatment of Dense Deposit Disease

Richard J.H Smith, Jessy Alexander, Paul N Barlow, Marina Botto, Thomas L Cassavant, H. Terence Cook, Santiago Rodriguez de Córdoba, Gregory S Hageman, T. Sakari Jokiranta, William J Kimberling, …
Journal of the American Society of Nephrology, Vol.18(9), pp.2447-2456
09/2007
DOI: 10.1681/ASN.2007030356
PMCID: PMC4853920
PMID: 17675665
url
https://doi.org/10.1681/ASN.2007030356View
Published (Version of record) Open Access

Abstract

The development of clinical treatment protocols usually relies on evidence-based guidelines that focus on randomized, controlled trials. For rare renal diseases, such stringent requirements can represent a significant challenge. Dense deposit disease (DDD; also known as membranoproliferative glomerulonephritis type II) is a prototypical rare disease. It affects only two to three people per million and leads to renal failure within 10 yr in 50% of affected children. On the basis of pathophysiology, this article presents a diagnostic and treatment algorithm for patients with DDD. Diagnostic tests should assess the alternative pathway of complement for abnormalities. Treatment options include aggressive BP control and reduction of proteinuria, and on the basis of pathophysiology, animal data, and human studies, plasma infusion or exchange, rituximab, sulodexide, and eculizumab are additional options. Criteria for treatment success should be prevention of progression as determined by maintenance or improvement in renal function. A secondary criterion should be normalization of activity levels of the alternative complement pathway as measured by C3/C3d ratios and C3NeF levels. Outcomes should be reported to a central repository that is now accessible to all clinicians. As the understanding of DDD increases, novel therapies should be integrated into existing protocols for DDD and evaluated using an open-label Bayesian study design.

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