Supplementary Material for: Increased Levels of Copeptin, a Surrogate Marker of Arginine Vasopressin, Are Associated with an Increased Risk of Chronic Kidney Disease in a General Population

<i>Background:</i> Our aim was to test if plasma copeptin, a stable surrogate marker of arginine vasopressin, predicts decline of glomerular filtration rate (GFR) and risk of chronic kidney disease (CKD). <i>Methods:</i> We measured copeptin and renal function at the Malmö Diet and Cancer Cardiovascular Cohort baseline exam and reassessed renal function after a follow-up time of 16.6 ± 1.5 years (n = 3,186). Furthermore, we defined CKD based on an estimated GFR (eGFR) calculated by the Modification of Diet in Renal Disease (MDRD) &lt;60 (CKD_60MDRD), &lt;45 (CKD_45MDRD) and &lt;30 (CKD_30MDRD) ml/min/1.73 m2. <i>Results:</i> After multivariate adjustment (gender, age, baseline eGFR, smoking status, systolic blood pressure, antihypertensive treatment and follow-up time), copeptin (beta-coefficient per 1 SD increment of copeptin) was independently associated with significantly greater annual decline of eGFR (ml/min/1.73 m2) according to the MDRD formula (OR 0.057, 95% CI 0.022-0.093; p = 0.001) as well as according to the CKD Epidemiology Collaboration (CKD-EPI) formula (OR 0.050, 95% CI 0.022-0.077; p &lt; 0.001). Each SD increment of copeptin independently predicted incident CKD_60MDRD (OR 1.19, 95% CI 1.04-1.36; p = 0.010), CKD_45MDRD (OR 1.33, 95% CI 1.04-1.71; p = 0.026) and CKD_30MDRD (OR 3.69, 95% CI 1.41-9.66; p = 0.008). The relationship between copeptin and CKD defined by CKD-EPI gave similar results. <i>Conclusion:</i> Our data suggest that increased levels of copeptin independently predict decline in eGFR and greater risk of new-onset CKD.

<i>研究背景：</i>本研究旨在探讨血浆copeptin（精氨酸加压素(arginine vasopressin)的稳定替代标志物）能否预测肾小球滤过率(glomerular filtration rate, GFR)下降及慢性肾脏病(chronic kidney disease, CKD)的发病风险。<i>研究方法：</i>本研究于马尔默饮食与癌症心血管队列的基线检查时检测了受试者的血浆copeptin水平与肾功能，并在平均随访16.6±1.5年后（n=3186）再次评估其肾功能。此外，本研究以肾脏病饮食调整研究(Modification of Diet in Renal Disease, MDRD)公式计算的估算肾小球滤过率(estimated GFR, eGFR)为依据定义慢性肾脏病：当eGFR<60 ml/min/1.73 m²时记为CKD_60MDRD，<45 ml/min/1.73 m²时记为CKD_45MDRD，<30 ml/min/1.73 m²时记为CKD_30MDRD。<i>研究结果：</i>经多因素校正（涵盖性别、年龄、基线eGFR、吸烟状态、收缩压、降压治疗情况及随访时长）后，copeptin水平每升高1个标准差(standard deviation, SD)，其与MDRD公式计算的eGFR年下降速率显著加快呈独立相关（β系数=0.057，95%置信区间(95% confidence interval, 95% CI)：0.022~0.093；p=0.001）；同时该关联在CKD-EPI公式计算的eGFR中同样显著（β系数=0.050，95% CI：0.022~0.077；p<0.001）。此外，copeptin水平每升高1个SD即可独立预测新发CKD_60MDRD（比值比(odds ratio, OR)=1.19，95% CI：1.04~1.36；p=0.010）、CKD_45MDRD（OR=1.33，95% CI：1.04~1.71；p=0.026）及CKD_30MDRD（OR=3.69，95% CI：1.41~9.66；p=0.008）的发生。以CKD-EPI标准定义的慢性肾脏病与copeptin水平间的关联亦得到了相似结果。<i>研究结论：</i>本研究数据表明，血浆copeptin水平升高可独立预测eGFR下降及新发慢性肾脏病的发病风险升高。