Section of Nephrology and Hypertension, 1st Department of Medicine, AHEPA Hospital, Thessaloniki, Greece.
Department of Nephrology, Hippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece.
Nephrol Dial Transplant. 2018 Nov 1;33(11):1887-1895. doi: 10.1093/ndt/gfy023.
Hypertension and progressive decline of renal function are among the common clinical manifestations in autosomal dominant polycystic kidney disease (ADPKD). At present, cyst formation in ADPKD patients is still considered the main pathogenic mechanism for the onset of these manifestations. However, the presence of polycystins in the vessels and the cilia of the endothelial cells and vascular smooth muscle cells, as well as development of hypertension prior to renal function decline and its prognostic role for the latter, indicate that polycystins may have an important role for endothelial damage in several vascular beds. Pathological polycystins induce intracellular calcium abnormalities, which affect various cellular organelles and functions and possibly lead not only to several abnormal biochemical reactions within endothelial cells, but also to an imbalance between oxidant and antioxidant capacity. Among the consequences of this process is accumulation of asymmetric-dimethylarginine, which not only participates in the induction and progression of renal damage, but also interferes with the normal vascular response due to nitric oxide (NO) inhibition. Reduced NO bioavailability would result in the long-run in relative vasoconstriction, impaired renal blood flow and vascular remodelling. This review summarizes the existing data from studies supporting that mechanisms other than cyst formation also contribute to the pathogenesis of hypertension and renal function decline in ADPKD.
高血压和肾功能进行性下降是常染色体显性多囊肾病（ADPKD）的常见临床表现之一。目前，ADPKD 患者的囊肿形成仍被认为是这些表现发生的主要发病机制。然而，多囊蛋白存在于血管内皮细胞和血管平滑肌细胞的血管和纤毛中，以及高血压在肾功能下降之前的发生及其对后者的预后作用，表明多囊蛋白可能在几个血管床的内皮损伤中具有重要作用。病理性多囊蛋白引起细胞内钙异常，影响各种细胞细胞器和功能，可能不仅导致内皮细胞内发生几种异常生化反应，还导致氧化应激和抗氧化能力之间失衡。该过程的后果之一是不对称二甲基精氨酸的积累，它不仅参与了肾损伤的诱导和进展，而且由于一氧化氮（NO）抑制，还干扰了正常的血管反应。NO 生物利用度降低会导致长期相对血管收缩、肾血流减少和血管重塑。本综述总结了现有研究数据，支持除囊肿形成以外的其他机制也有助于 ADPKD 中高血压和肾功能下降的发病机制。
