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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, John D. Lambris, Lynne D. Lanning^||||, Vicki Levidiotis^¶¶, Christoph Licht^***, Hans U. Lutz, Seppo Meri, Matthew C. Pickering, Richard J. Quigg, Angelique L. Rops, David J. Salant, Sanjeev Sethi^||||||, Joshua M. Thurman^¶¶¶, Hope F. Tully^****, Sean P. Tully^****, Johan van der Vlag, Patrick D. Walker, Reinhard Würzner, Peter F. Zipfel Dense Deposit Disease Focus Group

Departments of ^* Internal Medicine and Otolaryngology and ^** Ophthalmology and Visual Sciences, University of Iowa Carver College of Medicine, Iowa City, Iowa; Department of Internal Medicine, University of Chicago Hospitals, Chicago, Illinois; Institute of Structural and Molecular Biology, University of Edinburgh, King’s Buildings, Edinburgh, United Kingdom; Imperial College, Faculty of Medicine, London, England; ^|| Center for Bioinformatics and Computational Biology, University of Iowa, Iowa City, Iowa; ^¶ Centro de Investigaciones Biologicas, Madrid, Spain; Department of Bacteriology and Immunology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland; Boys Town National Research Hospital, Omaha, Nebraska; Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; ^|||| Kidneeds, Greater Cedar Rapids Community Foundation, Cedar Rapids, Iowa; ^¶¶ Royal Prince Alfred Hospital, Sydney, Australia; ^*** Department of Pediatrics, Hospital for Sick Children, Toronto, Canada; Institute of Biochemistry, Swiss Federal Institute of Technology, Zurich, Switzerland; Nephrology Research Laboratory, Division of Nephrology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands; Department of Medicine, Boston University Medical Center, Boston, Massachusetts; ^|||||| Department of Pathology, The Mayo Clinic, Rochester, Minnesota; ^¶¶¶ Department of Medicine, University of Colorado Health Sciences Center, Denver, Colorado; ^**** Milagros Research Fund, Chappaqua, New York, New York; Nephropathology Associates, Little Rock, Arkansas; Department of Hygiene, Microbiology and Social Medicine, Innsbruck Medical University, Innsbruck, Austria; and Leibniz Institute for Natural Product Research and Infection Biology and Friedrich Schiller University, Jena, Germany

Correspondence: Dr. Richard J.H. Smith, 200 Hawkins Drive, 21151 PFP, University of Iowa, Iowa City, IA 52242. Phone: 319-356-3612; Fax: 319-356-4108; E-mail: richard-smith{at}uiowa.edu

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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				P. F. Zipfel, R. J. H. Smith, and C. Skerka Factor I and Factor H deficiency in renal diseases: similar defects in the fluid phase have a different outcome at the surface of the glomerular basement membrane Nephrol. Dial. Transplant., December 4, 2008; (2008) gfn652v1. [Full Text] [PDF]

Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673