Section of Nephrology, Hypertension and Kidney Transplantation, Temple University, Philadelphia, PA, USA.
Nephrol Dial Transplant. 2012 Nov;27(11):4166-72. doi: 10.1093/ndt/gfs337. Epub 2012 Aug 20.
The TAM receptors (tyro3, axl and mer) and their ligands (vitamin K-dependent proteins-Gas6 and Protein S) are crucial modulators of inflammation, which may be relevant in chronic kidney disease (CKD). Gas6 and axl have multiple roles in mediating vascular atherosclerosis and injury, thrombosis and inflammation, yet nothing is known about the Gas6-axl pathway in humans with CKD. Given the prevalence of chronic inflammation and vascular disease in this population, we measured TAM ligands in patients with various levels of renal function.
Gas6 and protein S were quantified in the plasma by ELISA in three patient groups: end-stage renal disease on chronic hemodialysis (HD), CKD and normal controls.
Significantly increased levels of Gas6 and protein S were found in CKD patients compared with normal controls (P < 0.01 and <0.001, respectively). In HD patients, Gas6 levels were elevated compared with controls (P < 0.001) and positively associated with low albumin (r = 0.33; P = 0.01), dialysis vintage (r = 0.36; P = 0.008) and IV iron administration (r = 0.33; P = 0.01). The levels of Gas6 rose with CKD stage and were inversely associated with estimated GFR (P < 0.0001).
Dysregulation of circulating Gas6 is associated with renal disease and inversely proportional to renal function. Low albumin and higher IV iron administration were associated with higher Gas6 levels, suggesting a possible connection between inflammation and oxidative stress mediated by iron. Protein S levels were also elevated in CKD patients, but the relevance of this finding needs to be further investigated.
TAM 受体（tyro3、axl 和 mer）及其配体（维生素 K 依赖性蛋白-Gas6 和蛋白 S）是炎症的关键调节剂，这在慢性肾脏病（CKD）中可能是相关的。Gas6 和 axl 在介导血管动脉粥样硬化和损伤、血栓形成和炎症方面具有多种作用，但在 CKD 患者中，Gas6-axl 通路尚不清楚。鉴于该人群中慢性炎症和血管疾病的高发率，我们测量了肾功能不同水平的患者的 TAM 配体。
通过 ELISA 法在三组患者中测量了 Gas6 和蛋白 S 的血浆浓度：慢性血液透析（HD）终末期肾衰竭患者、CKD 患者和正常对照组。
与正常对照组相比，CKD 患者的 Gas6 和蛋白 S 水平显著升高（P < 0.01 和 <0.001）。在 HD 患者中，Gas6 水平与对照组相比升高（P < 0.001），与低白蛋白（r = 0.33；P = 0.01）、透析龄（r = 0.36；P = 0.008）和静脉铁剂治疗（r = 0.33；P = 0.01）呈正相关。Gas6 水平随 CKD 分期升高，并与估计的肾小球滤过率呈反比（P < 0.0001）。
循环 Gas6 的失调与肾脏疾病相关，并与肾功能成反比。低白蛋白和更高的静脉铁剂治疗与更高的 Gas6 水平相关，这表明炎症和铁介导的氧化应激之间可能存在联系。CKD 患者的蛋白 S 水平也升高，但这一发现的相关性需要进一步研究。
