The Kidney Institute, Division of Nephrology and Hypertension, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, Kansas 66160, USA.
Division of Nephrology and Hypertension, Mayo Clinic, 200 First Street SW, Minnesota 55905, USA.
Nat Rev Nephrol. 2016 Nov;12(11):667-677. doi: 10.1038/nrneph.2016.135. Epub 2016 Oct 3.
The rate at which autosomal dominant polycystic kidney disease (ADPKD) progresses to end-stage renal disease varies widely and is determined by genetic and non-genetic factors. The ability to determine the prognosis of children and young adults with ADPKD is important for the effective life-long management of the disease and to enable the efficacy of emerging therapies to be determined. Total kidney volume (TKV) reflects the sum volume of hundreds of individual cysts with potentially devastating effects on renal function. The sequential measurement of TKV has been advanced as a dynamic biomarker of disease progression, yet doubt remains among nephrologists and regulatory agencies as to its usefulness. Here, we review the mechanisms that lead to an increase in TKV in ADPKD, and examine the evidence supporting the conclusion that TKV provides a metric of disease progression that can be used to assess the efficacy of potential therapeutic regimens in children and adults with ADPKD. Moreover, we propose that TKV can be used to monitor treatment efficacy in patients with normal levels of renal function, before the pathologic processes of ADPKD cause extensive fibrosis and irreversible loss of functioning renal tissue.
常染色体显性遗传多囊肾病（ADPKD）进展为终末期肾病的速度差异很大，由遗传和非遗传因素决定。能够确定 ADPKD 患儿和青年患者的预后对于有效管理疾病的终身治疗以及确定新兴疗法的疗效非常重要。总肾体积（TKV）反映了数百个个体囊肿的总和体积，对肾功能具有潜在的破坏性影响。TKV 的连续测量已被提出作为疾病进展的动态生物标志物，但肾病学家和监管机构对其有用性仍存在疑问。在这里，我们回顾了导致 ADPKD 中 TKV 增加的机制，并检查了支持 TKV 提供疾病进展衡量标准的结论的证据，该标准可用于评估儿童和成人 ADPKD 中潜在治疗方案的疗效。此外，我们提出 TKV 可用于在 ADPKD 的病理过程导致广泛纤维化和不可逆转的功能丧失的肾组织之前，监测肾功能正常患者的治疗效果。
