Division of Nephrology, National Yang-Ming University Hospital, Yilan, Taiwan.
PLoS One. 2013 Jul 26;8(7):e70132. doi: 10.1371/journal.pone.0070132. Print 2013.
Circulating matrix metalloproteinase (MMP)-2, -3 and -9 are well recognized in predicting cardiovascular outcome in coronary artery disease (CAD), but their risks for chronic kidney disease (CKD) are lacking. Therefore, the present study aimed to investigate whether circulating MMP levels could independently predict future kidney disease progression in non-diabetic CAD patients.
The prospective study enrolled 251 non-diabetic subjects referred for coronary angiography, containing normal coronary artery (n = 30) and CAD with insignificant (n = 95) and significant (n = 126) stenosis. Estimated glomerular filtration rate (eGFR) was calculated using the CKD-EPI formula. eGFR decline rate was calculated and the primary endpoint was a decline in eGFR over 25% from baseline.
The eGFR decline rate (ml/min/1.73 m(2) per year) in patients with CAD (1.22 [-1.27, 1.05]) was greater than that in those with normal coronary artery (0.21 [-2.63, 0.47], P<0.01). The circulating MMP-2, -3 and -9 were independently associated with faster eGFR decline among CAD patients. The mean follow-up period was 8.5±2.4 years, and 39 patients reached the primary endpoint. In multivariate Cox regression model, the adjusted hazard ratios of MMP-2 ≥861 ng/mL, MMP-3 ≥227 ng/mL and MMP-9 ≥49 ng/mL for predicting CKD progression were 2.47 (95% CI, 1.21 to 5.07), 2.15 (1.12 to 4.18), and 4.71 (2.14 to 10.4), respectively. While added to a model of conventional risk factors and baseline eGFR, MMP-2, -3 and -9 further significantly improved the model predictability for CKD progression (c statistic, 0.817). In the sensitivity analyses, the results were similar no matter if we changed the endpoints of a decline of >20% in eGFR from baseline or final eGFR < 60 mL/min/1.73 m(2).
Circulating MMP-2, -3 and -9 are independently associated with kidney disease progression in non-diabetic CAD patients and add incremental predictive power to conventional risk factors.
循环基质金属蛋白酶（MMP）-2、-3 和 -9 已被广泛认可，可用于预测冠状动脉疾病（CAD）中的心血管结局，但它们对慢性肾脏病（CKD）的风险尚不清楚。因此，本研究旨在探讨非糖尿病 CAD 患者中循环 MMP 水平是否可独立预测未来的肾脏疾病进展。
前瞻性研究纳入了 251 例因冠状动脉造影而就诊的非糖尿病患者，包括正常冠状动脉（n=30）和无明显狭窄（n=95）和明显狭窄（n=126）的 CAD。使用 CKD-EPI 公式计算估算肾小球滤过率（eGFR）。计算 eGFR 下降率，主要终点是 eGFR 从基线下降 25%以上。
CAD 患者的 eGFR 下降率（ml/min/1.73 m(2)每年）为 1.22 [-1.27, 1.05]，大于正常冠状动脉患者的 0.21 [-2.63, 0.47]，P<0.01）。循环 MMP-2、-3 和 -9 与 CAD 患者的 eGFR 下降速度独立相关。多变量 Cox 回归模型中，MMP-2≥861ng/ml、MMP-3≥227ng/ml 和 MMP-9≥49ng/ml 预测 CKD 进展的调整后危险比分别为 2.47（95%CI，1.21 至 5.07）、2.15（1.12 至 4.18）和 4.71（2.14 至 10.4）。当添加到常规危险因素和基线 eGFR 的模型中时，MMP-2、-3 和 -9 进一步显著提高了 CKD 进展的模型预测能力（c 统计量，0.817）。在敏感性分析中，无论我们是否将 eGFR 从基线下降>20%或最终 eGFR<60mL/min/1.73 m(2)作为终点，结果均相似。
循环 MMP-2、-3 和 -9 与非糖尿病 CAD 患者的肾脏疾病进展独立相关，并为常规危险因素提供了额外的预测能力。
