Drechsler Christiane, Delgado Graciela, Wanner Christoph, Blouin Katja, Pilz Stefan, Tomaschitz Andreas, Kleber Marcus E, Dressel Alexander, Willmes Christoph, Krane Vera, Krämer Bernhard K, März Winfried, Ritz Eberhard, van Gilst Wiek H, van der Harst Pim, de Boer Rudolf A
Division of Nephrology, Department of Internal Medicine 1 and Comprehensive Heart Failure Centre, University Hospital of Würzburg, Würzburg, Germany;
Fifth Department of Medicine, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany;
J Am Soc Nephrol. 2015 Sep;26(9):2213-21. doi: 10.1681/ASN.2014010093. Epub 2015 Jan 7.
Galectin-3 has been linked to incident renal disease, experimental renal fibrosis, and nephropathy. However, the association among galectin-3, renal function, and adverse outcomes has not been described. We studied this association in two large cohorts of patients over a broad range of renal function. We measured galectin-3 concentrations in baseline samples from the German Diabetes mellitus Dialysis (4D) study (1168 dialysis patients with type 2 diabetes mellitus) and the Ludwigshafen Risk and Cardiovascular Health (LURIC) study (2579 patients with coronary angiograms). Patients were stratified into three groups: eGFR of ≥90 ml/min per 1.73 m(2), 60-89 ml/min per 1.73 m(2), and <60 ml/min per 1.73 m(2). We correlated galectin-3 concentrations with demographic, clinical, and biochemical parameters. The association of galectin-3 with clinical end points was assessed by Cox proportional hazards regression within 10 years (LURIC) or 4 years (4D) of follow-up. Mean±SD galectin-3 concentrations were 12.8±4.0 ng/ml (eGFR≥90 ml/min per 1.73 m(2)), 15.6±5.4 ng/ml (eGFR 60-89 ml/min per 1.73 m(2)), 23.1±9.9 ng/ml (eGFR<60 ml/min per 1.73 m(2)), and 54.1±19.6 ng/ml (dialysis patients of the 4D study). Galectin-3 concentration was significantly associated with clinical end points in participants with impaired kidney function, but not in participants with normal kidney function. Per SD increase in log-transformed galectin-3 concentration, the risks of all-cause mortality, cardiovascular mortality, and fatal infection increased significantly. In dialysis patients, galectin-3 was associated with the combined end point of cardiovascular events. In conclusion, galectin-3 concentrations increased with progressive renal impairment and independently associated with cardiovascular end points, infections, and all-cause death in patients with impaired renal function.
半乳糖凝集素-3与新发肾病、实验性肾纤维化及肾病相关。然而,半乳糖凝集素-3、肾功能及不良结局之间的关联尚未见描述。我们在两个具有广泛肾功能范围的大型患者队列中研究了这种关联。我们测量了来自德国糖尿病透析(4D)研究(1168例2型糖尿病透析患者)和路德维希港风险与心血管健康(LURIC)研究(2579例接受冠状动脉造影的患者)的基线样本中的半乳糖凝集素-3浓度。患者被分为三组:估算肾小球滤过率(eGFR)≥90 ml/(min·1.73 m²)、60 - 89 ml/(min·1.73 m²)以及<60 ml/(min·1.73 m²)。我们将半乳糖凝集素-3浓度与人口统计学、临床及生化参数进行关联分析。通过Cox比例风险回归评估半乳糖凝集素-3与临床终点在10年(LURIC研究)或4年(4D研究)随访期内的关联。平均±标准差半乳糖凝集素-3浓度分别为12.8±4.0 ng/ml(eGFR≥90 ml/(min·1.73 m²))、15.6±5.4 ng/ml(eGFR 60 - 89 ml/(min·1.73 m²))、23.1±9.9 ng/ml(eGFR<60 ml/(min·1.73 m²))以及54.1±19.6 ng/ml(4D研究中的透析患者)。在肾功能受损的参与者中,半乳糖凝集素-3浓度与临床终点显著相关,但在肾功能正常的参与者中并非如此。经对数转换的半乳糖凝集素-3浓度每增加1个标准差,全因死亡率、心血管死亡率及致命感染风险均显著增加。在透析患者中,半乳糖凝集素-3与心血管事件的联合终点相关。总之,半乳糖凝集素-3浓度随肾功能进行性损害而升高,并与肾功能受损患者的心血管终点、感染及全因死亡独立相关。