Xu Ting-Yan, Zhang Yi, Li Yan, Zhu Ding-Liang, Gao Ping-Jin
State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension and Department of Hypertension, Ruijin Hospital, Shanghai Jiaotong University School of Medicine , Shanghai , China .
Ren Fail. 2014 Jun;36(5):666-72. doi: 10.3109/0886022X.2014.890002. Epub 2014 Feb 27.
A positive association between inflammation and chronic kidney disease (CKD) has been reported but the impact of hypertension on this relation remains unclear. The aim of this study is to investigate the association of various inflammation markers with risk of CKD in hypertensive patients. 387 hypertensive patients (mean age 55.5 years) were recruited. Serum matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1(TIMP-1), high-sensitivity C-reactive protein (hsCRP) and osteopontin (OPN) were measured by ELISA. CKD was diagnosed either as evidence of kidney damage, including microalbuminuria, or by low glomerular filtration rate (GFR) (<60 mL/min/1.73 m(2)), which was estimated using the Modification of Diet in Renal Disease (MDRD) abbreviated equation. Compared with the reference groups (eGFR ≥ 60 mL/min/1.73 m(2)), the serum levels of TIMP-1, OPN, hsCRP were significantly higher, and the MMP-9/TIMP-1 ratio was lower in the risk group (eGFR < 60 mL/min/1.73 m(2)). Multiple logistic regression analysis showed that TIMP-1, MMP-9/TIMP-1 ratio, OPN and hsCRP were associated with low GFR separately after adjustment, whereas MMP-9/TIMP-1 ratio, OPN and hsCRP were associated with microalbuminuria. The significant association of MMP-9/TIMP-1 ratio and OPN with low GFR and microalbuminuria persisted after additional adjustment for other studied inflammatory biomarkers. Our data suggest that inflammation is strongly and independently associated with renal damage in hypertensive patients. MMP-9/TIMP-1 ratio and OPN may serve as novel risk factors and therapeutic targets for the treatment of CKD in hypertensive patients.
炎症与慢性肾脏病(CKD)之间的正相关关系已有报道,但高血压对这种关系的影响仍不明确。本研究的目的是调查高血压患者中各种炎症标志物与CKD风险的关联。招募了387名高血压患者(平均年龄55.5岁)。采用酶联免疫吸附测定法(ELISA)检测血清基质金属蛋白酶-2(MMP-2)、基质金属蛋白酶-9(MMP-9)、金属蛋白酶组织抑制剂-1(TIMP-1)、高敏C反应蛋白(hsCRP)和骨桥蛋白(OPN)。CKD的诊断依据为肾脏损伤证据,包括微量白蛋白尿,或通过低肾小球滤过率(GFR)(<60 mL/min/1.73 m²),后者使用肾脏病饮食改良(MDRD)简化方程估算。与参照组(估算肾小球滤过率[eGFR]≥60 mL/min/1.73 m²)相比,风险组(eGFR<60 mL/min/1.73 m²)的血清TIMP-1、OPN、hsCRP水平显著更高,而MMP-9/TIMP-1比值更低。多因素逻辑回归分析显示,调整后TIMP-1、MMP-9/TIMP-1比值、OPN和hsCRP分别与低GFR相关,而MMP-9/TIMP-1比值、OPN和hsCRP与微量白蛋白尿相关。在对其他研究的炎症生物标志物进行额外调整后,MMP-9/TIMP-1比值和OPN与低GFR及微量白蛋白尿之间的显著关联依然存在。我们的数据表明,炎症与高血压患者的肾脏损伤密切且独立相关。MMP-9/TIMP-1比值和OPN可能作为高血压患者CKD治疗的新危险因素和治疗靶点。