Division of Nephrology, Department of Medicine, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908, USA.
Clin J Am Soc Nephrol. 2013 Jul;8(7):1098-105. doi: 10.2215/CJN.09170912. Epub 2013 Jun 6.
There are no effective therapies for malnutrition in CKD/ESRD patients. This study hypothesized that ghrelin, an endogenous orexigenic hormone, would correlate with renal function and might suggest therapeutic interventions for CKD/ESRD malnutrition.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Fifty-one CKD and 15 hemodialysis patients were enrolled. Acyl ghrelin (AG) and des-acyl ghrelin (DG) were determined using separate two-site-specific assays. Leptin, insulin, growth hormone, insulin-link growth factor-1, C-reactive protein, TNF-α, and IL-6 were also measured.
Univariate correlation analyses showed that CKD stage was highly, positively correlated with the levels of preprandial and postprandial DG and positively correlated with TNF-α, IL-6, leptin, and age. Multivariate partial-correlation analyses showed that CKD was independently associated with the proportion of preprandial and postprandial DG, whereas TNF-α, IL-6, leptin, insulin, and age were not independently associated with either. Geometric mean (GM) preprandial and postprandial AG were comparable between CKD stages ≤2 and >2, whereas GM preprandial DG and postprandial DG were 1.95-fold and 2.17-fold greater, respectively, for CKD stage >2 versus stage ≤2. DG was the dominant form of ghrelin preprandially and postprandially for both CKD stages ≤2 and >2. Dialysis had no effect on AG, but reduced DG by 73% to levels even lower (GM 48.7 pg/ml) than those seen postprandially in CKD stage ≤2 patients (GM 77.0 pg/ml).
This study shows a strong and independent correlation of DG with CKD stage. Postprandial suppression of ghrelin is impaired with reduced renal function. Hemodialysis selectively removes DG but not AG.
目前针对 CKD/ESRD 患者营养不良尚无有效疗法。本研究假设内源性食欲刺激激素——ghrelin 与肾功能相关,可能为 CKD/ESRD 患者营养不良的治疗提供新靶点。
设计、地点、对象和测量方法:共纳入 51 例 CKD 患者和 15 例血液透析患者。采用双位点特异性检测法分别检测酰基 ghrelin(AG)和去酰基 ghrelin(DG)。同时检测瘦素、胰岛素、生长激素、胰岛素样生长因子-1、C 反应蛋白、TNF-α 和 IL-6。
单变量相关分析显示,CKD 分期与餐前和餐后 DG 水平呈高度正相关,与 TNF-α、IL-6、瘦素和年龄呈正相关。多变量偏相关分析显示,CKD 与餐前和餐后 DG 比例独立相关,而 TNF-α、IL-6、瘦素、胰岛素和年龄与餐前和餐后 DG 比例均无独立相关性。与 CKD 分期≤2 期患者相比,CKD 分期>2 期患者的餐前和餐后 AG 的几何均数(GM)无差异,而餐前和餐后 DG 的 GM 分别升高 1.95 倍和 2.17 倍。DG 是 CKD 分期≤2 和>2 期患者餐前和餐后主要的 ghrelin 形式。透析对 AG 无影响,但降低 DG 达 73%,使 DG 水平(GM 48.7pg/ml)甚至低于 CKD 分期≤2 期患者餐后水平(GM 77.0pg/ml)。
本研究显示 DG 与 CKD 分期有强烈且独立的相关性。肾功能下降导致餐后 ghrelin 抑制受损。血液透析选择性清除 DG,但不清除 AG。