Kocyigit Ismail, Sener Elif Funda, Taheri Serpil, Eroglu Eray, Ozturk Fahir, Unal Aydin, Zararsiz Gokmen, Uzun Ilknur, Imamoglu Hakan, Sipahioglu Murat Hayri, Tokgoz Bulent, Oymak Oktay, Ecder Tevfik
Erciyes University Medical Faculty, Department of Internal Medicine, Division of Nephrology, Kayseri, Turkey.
Erciyes University Medical Faculty, Department of Medical Biology, Kayseri, Turkey.
Ther Apher Dial. 2016 Dec;20(6):615-622. doi: 10.1111/1744-9987.12458. Epub 2016 Dec 7.
Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary cause of chronic kidney disease. The intriguing role of innate immune system and inflammation become a target for potential therapeutic approach to slow progression. When toll-like receptors (TLRs) signaling and their receptors activate, they start a cascade of intracellular signaling that induces the production of the inflammatory cytokines and chemokines. Thus, we aim to investigate the association of TLRs between progression of ADPKD. Ninety ADPKD patients and ninety matched controls were enrolled this prospective study and were followed during 3 years. TLR-2 and TLR-4 gene polymorphisms and expressions were measured. Hypertension was diagnosed with ambulatory blood pressure monitoring. Rapid progression was defined as sustained decline in estimated glomerular filtration rate (eGFR) of more than 5 mL/min per 1.73 m per year. TLR-4Asp299Gly polymorphisms were significantly different between patient and control group (P < 0.05). Also, TLR-2 and TLR-4 gene expressions were significantly different between the ADPKD patients and the control subjects (P < 0.05). The expression levels of both TLR-2 and TLR-4 were found to be higher in the rapid progression groups comparing the slow progression group (P < 0.05). TLR-2 gene expression, hypertension and uric acid were found to be independent risk factors in identifying rapid progression in ADPKD patients. TLR-2 and TLR-4 gene expressions are associated with rapid progression in ADPKD patients. TLRs may play a role in the progression of ADPKD.
常染色体显性遗传性多囊肾病（ADPKD）是慢性肾病最常见的遗传病因。固有免疫系统和炎症的有趣作用成为减缓疾病进展的潜在治疗方法的靶点。当Toll样受体（TLR）信号及其受体激活时，它们会启动一系列细胞内信号传导，诱导炎性细胞因子和趋化因子的产生。因此，我们旨在研究TLR与ADPKD进展之间的关联。本前瞻性研究纳入了90例ADPKD患者和90例匹配的对照，并对其进行了3年的随访。检测了TLR-2和TLR-4基因多态性及表达情况。通过动态血压监测诊断高血压。快速进展定义为估计肾小球滤过率（eGFR）每年持续下降超过5 mL/min/1.73 m²。患者组和对照组之间TLR-4 Asp299Gly多态性存在显著差异（P < 0.05）。此外，ADPKD患者与对照受试者之间TLR-2和TLR-4基因表达也存在显著差异（P < 0.05）。与缓慢进展组相比，快速进展组中TLR-2和TLR-4的表达水平均更高（P < 0.05）。发现TLR-2基因表达、高血压和尿酸是识别ADPKD患者快速进展的独立危险因素。TLR-2和TLR-4基因表达与ADPKD患者的快速进展相关。TLR可能在ADPKD的进展中起作用。
