Total Kidney Volume in Autosomal Dominant Polycystic Kidney Disease: A Biomarker of Disease Progression and Therapeutic Efficacy
Total Kidney Volume in Autosomal Dominant Polycystic Kidney Disease: A Biomarker of Disease Progression and Therapeutic Efficacy
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DOI：
10.1053/j.ajkd.2015.01.030
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发表时间：
2015-10-01
影响因子：
13.2
通讯作者：
Bichet, Daniel G.
中科院分区：
文献类型：
--
作者：
Alam, Ahsan;Dahl, Neera K.;Bichet, Daniel G.
常染色体显性多囊肾病（ADPKD）是人类最常见的潜在威胁生命的单基因疾病，其特征是肾脏和其他器官中充满液体的囊肿逐渐发展和扩大。持续的囊肿生长导致肾脏进行性增大，而由于未受影响的肾单位的超滤和代偿，肾脏功能在几十年内保持稳定。只有在疾病的晚期，当大部分实质组织被囊性和纤维化组织所取代，剩余的代偿能力被淹没时，肾功能才会不可逆转地下降。因此，传统的肾功能测量，如肾小球滤过率，不能充分评估ADPKD的疾病进展，特别是在其早期阶段。鉴于最近ADPKD潜在靶向治疗的发展，鉴定相关的生物标志物变得至关重要，这些生物标志物可用于确定疾病进展程度并评估治疗干预对疾病进程的影响。我们回顾了目前的证据，以提供一个知情的观点，即总肾容量（TKV）是否是疾病进展的合适生物标志物，以及TKV是否可以用作临床试验的疗效终点。我们的结论是，由于膀胱形成是导致肾脏增大的主要因素，TKV似乎是一个合适的生物标志物，并正在获得更广泛的接受。一些研究已经确定TKV是监测和预测疾病进展的相关成像生物标志物，并支持将其用作临床试验的预后终点。(C) 2015年由国家肾脏基金会，Inc。
Autosomal dominant polycystic kidney disease (ADPKD) is the most common potentially life-threatening monogenic disorder in humans, characterized by progressive development and expansion of fluid-filled cysts in the kidneys and other organs. Ongoing cyst growth leads to progressive kidney enlargement, whereas kidney function remains stable for decades as a result of hyperfiltration and compensation by unaffected nephrons. Kidney function irreversibly declines only in the late stages of the disease, when most of the parenchyma is lost to cystic and fibrotic tissue and the remaining compensatory capacity is overwhelmed. Hence, conventional kidney function measures, such as glomerular filtration rate, do not adequately assess disease progression in ADPKD, especially in its early stages. Given the recent development of potential targeted therapies in ADPKD, it has become critically important to identify relevant biomarkers that can be used to determine the degree of disease progression and evaluate the effects of therapeutic interventions on the course of the disease. We review the current evidence to provide an informed perspective on whether total kidney volume (TKV) is a suitable biomarker for disease progression and whether TKV can be used as an efficacy end point in clinical trials. We conclude that because cystogenesis is the central factor leading to kidney enlargement, TKV appears to be an appropriate biomarker and is gaining wider acceptance. Several studies have identified TKV as a relevant imaging biomarker for monitoring and predicting disease progression and support its use as a prognostic end point in clinical trials. (C) 2015 by the National Kidney Foundation, Inc.