Krane Vera, Genser Bernd, Kleber Marcus E, Drechsler Christiane, März Winfried, Delgado Graciela, Allolio Bruno, Wanner Christoph, Fenske Wiebke
Department of Medicine 1, Division of Nephrology, and
Comprehensive Heart Failure Centre, University Hospital of Würzburg, Würzburg, Germany.
Clin Chem. 2017 May;63(5):997-1007. doi: 10.1373/clinchem.2016.266254. Epub 2017 Mar 9.
In chronic kidney disease (CKD) arginine vasopressin (AVP) cannot efficiently act via renal V2-receptors. AVP is upregulated leading to augmented activation of V1a- and V1b-receptors, which might contribute to the increase in cardiovascular and infectious complications in CKD. Here, we evaluate copeptin, a surrogate of AVP, and its association with cause specific mortality among patients within the whole spectrum of renal function.
Copeptin was measured in baseline samples from the LURIC (n = 3131 patients with coronary angiograms) and the 4D-Study (n = 1241 type 2 diabetic hemodialysis patients). Patients were stratified into 4 groups: estimated glomerular filtration rate (eGFR) ≥90 mL/min/1.73 m, 60-89 mL/min/1.73 m, <60 mL/min/1.73 m, and hemodialysis. The association of copeptin with mortality was assessed by Cox proportional hazards regression during 9.9 years of median follow-up in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study and 4 years of median follow-up in the German Diabetes Dialysis Study (4D-Study).
Median copeptin increased with decreasing eGFR: 5.6 [interquartile range (IQR), 3.1-8.1] pmol/L (eGFR ≥90 mL/min/1.73 m), 6.7 (2.9-10.5) pmol/L (eGFR 60-89 mL/min/1.73 m), 15.3 (6.7-23.9) pmol/L (eGFR <60 mL/min/1.73 m), and 80.8 (51.2-122) pmol/L (hemodialysis), respectively. Per SD increase in copeptin, the risk of coronary, infectious, and all-cause mortality increased by 25, 30, and 15% [hazard ratios (HR), 1.25; 95% CI, 1.13-1.39; HR, 1.30; 95% CI, 0.98-1.71; and HR, 1.15; 95% CI, 1.05-1.25], respectively, in patients with eGFR 60-89 mL/min/1.73 m. Except for coronary death, results were similar among patients with more advanced renal disease. No significant association was found in patients with normal renal function.
Copeptin concentrations were independently associated with coronary, infectious, and all-cause mortality in patients with renal impairment. In patients with normal renal function no significant association was found.
在慢性肾脏病（CKD）中，精氨酸加压素（AVP）无法通过肾脏V2受体有效发挥作用。AVP上调，导致V1a和V1b受体的激活增强，这可能导致CKD患者心血管和感染并发症增加。在此，我们评估了作为AVP替代指标的 copeptin，并探讨其与全肾功能范围内患者特定病因死亡率的关系。
在LURIC研究（n = 3131例接受冠状动脉造影的患者）和4D研究（n = 1241例2型糖尿病血液透析患者）的基线样本中检测copeptin。患者被分为4组：估计肾小球滤过率（eGFR）≥90 mL/min/1.73 m²、60 - 89 mL/min/1.73 m²、<60 mL/min/1.73 m²和血液透析组。在路德维希港风险与心血管健康（LURIC）研究中位随访9.9年以及德国糖尿病透析研究（4D研究）中位随访四年期间，通过Cox比例风险回归评估copeptin与死亡率的关系。
随着eGFR降低，copeptin中位数升高：分别为5.6 [四分位间距（IQR），3.1 - 8.1] pmol/L（eGFR≥90 mL/min/1.73 m²）、6.7（2.9 - 10.5）pmol/L（eGFR 60 - 89 mL/min/1.73 m²）、15.3（6.7 - 23.9）pmol/L（eGFR <60 mL/min/1.73 m²）和80.8（51.2 - 122）pmol/L（血液透析）。在eGFR为60 - 89 mL/min/1.73 m²的患者中，copeptin每增加1个标准差，冠状动脉、感染和全因死亡率风险分别增加25%、30%和15% [风险比（HR），1.25；95% CI，1.13 - 1.39；HR，1.30；95% CI，0.98 - 1.71；HR，1.15；95% CI，1.05 - 1.25]。除冠状动脉死亡外，在更晚期肾病患者中结果相似。在肾功能正常的患者中未发现显著关联。
copeptin浓度与肾功能损害患者的冠状动脉、感染和全因死亡率独立相关。在肾功能正常的患者中未发现显著关联。
