Smith Richard J H, Alexander Jessy, Barlow Paul N, Botto Marina, Cassavant Thomas L, Cook H Terence, de Córdoba Santiago Rodriguez, Hageman Gregory S, Jokiranta T Sakari, Kimberling William J, Lambris John D, Lanning Lynne D, Levidiotis Vicki, Licht Christoph, Lutz Hans U, Meri Seppo, Pickering Matthew C, Quigg Richard J, Rops Angelique L, Salant David J, Sethi Sanjeev, Thurman Joshua M, Tully Hope F, Tully Sean P, van der Vlag Johan, Walker Patrick D, Würzner Reinhard, Zipfel Peter F
Department of Internal Medicine and Otolaryngology, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA.
J Am Soc Nephrol. 2007 Sep;18(9):2447-56. doi: 10.1681/ASN.2007030356. Epub 2007 Aug 5.
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.
临床治疗方案的制定通常依赖于以随机对照试验为重点的循证指南。对于罕见肾病而言，如此严格的要求可能构成重大挑战。致密物沉积病（DDD；也称为II型膜增生性肾小球肾炎）就是一种典型的罕见病。该病每百万人口中仅有两到三人患病，50% 的患病儿童会在10年内发展为肾衰竭。基于病理生理学，本文提出了致密物沉积病患者的诊断和治疗算法。诊断测试应评估补体替代途径是否存在异常。治疗选择包括积极控制血压和减少蛋白尿，并且基于病理生理学、动物数据和人体研究，血浆输注或置换、利妥昔单抗、舒洛地昔和依库珠单抗也是可供选择的治疗方法。治疗成功的标准应以肾功能维持或改善所确定的病情进展预防情况为准。次要标准应以通过C3/C3d比值和C3NeF水平所测定的替代补体途径活性水平正常化为准。治疗结果应上报至一个所有临床医生均可访问的中央数据库。随着对致密物沉积病的了解不断增加，新疗法应纳入现有的致密物沉积病治疗方案，并采用开放标签贝叶斯研究设计进行评估。
