Inherited Renal Disorders, Nephrology Department, Fundació Puigvert, REDINREN, IIB Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
Nephrol Dial Transplant. 2019 Aug 1;34(8):1272-1279. doi: 10.1093/ndt/gfz131.
Alport syndrome (AS) is the most frequent inherited kidney disease after autosomal dominant polycystic kidney disease. It has three different patterns of inheritance-autosomal dominant, autosomal recessive and X-linked-which in part explains the wide spectrum of disease, ranging from isolated microhaematuria to end-stage renal disease early in life. The search for a treatment for AS is being pursued vigorously, not only because of the obvious unmet need but also because AS is a rare disease and any drug approved will have an orphan drug designation with its various benefits. Moreover, AS patients are quite young with very few comorbidities, which facilitates clinical trials. This review identifies the particularities of each pattern of inheritance but focuses mainly on new drugs or therapeutic targets for the disease. Most treatment-related investigations are directed not at the main abnormality in AS, namely collagen IV composition, but rather at the associated inflammation and fibrosis. Thus, AS may serve as a proof of concept for numerous drugs of potential value in many diseases that cause chronic kidney disease.
Alport 综合征（AS）是继常染色体显性多囊肾病之后最常见的遗传性肾脏疾病。它有三种不同的遗传模式——常染色体显性遗传、常染色体隐性遗传和 X 连锁遗传——这在一定程度上解释了该病广泛的临床表现谱，从孤立性镜下血尿到生命早期的终末期肾病不等。目前正在积极寻找 AS 的治疗方法，这不仅是因为明显的未满足的需求，还因为 AS 是一种罕见病，任何被批准的药物都将具有孤儿药的指定，并带来各种益处。此外，AS 患者非常年轻，合并症很少，这有利于临床试验。本文综述了每种遗传模式的特殊性，但主要集中在该疾病的新药或治疗靶点上。大多数与治疗相关的研究不是针对 AS 的主要异常，即胶原 IV 组成，而是针对相关的炎症和纤维化。因此，AS 可能成为许多具有潜在价值的药物在许多导致慢性肾病的疾病中的概念验证。
