Background:PENK (proenkephalin) is a stable surrogate for enkephalins, endogenous opioid peptides, which exert cardiodepressive effects and improve renal function. PENK has been associated with heart failure (HF) severity and renal dysfunction. We therefore hypothesized that PENK could be associated with deterioration of kidney function and could have a role as a novel renal marker in HF.Methods and Results:In 2180 patients with HF of a large multicenter cohort (BIOSTAT-CHF [A Systems Biology Study to Tailored Treatment in Chronic Heart Failure]), the relationship between PENK and clinical variables, plasma and urinary biomarkers, and clinical end points was established. Data were validated in a separate cohort of 1703 patients with HF. PENK was elevated (>80 pmol/L, 99th percentile) in 1245 (57%) patients. Higher PENK was associated with more advanced HF and glomerular and tubular dysfunction. The strongest independent predictor of PENK was estimated glomerular filtration rate. Others were plasma NGAL (neutrophil gelatinase–associated lipocalin) and NT-proBNP (N-terminal pro-B-type natriuretic peptide; all P<0.001). Using correlation heatmaps and hierarchical cluster analyses, PENK clustered with estimated glomerular filtration rate, creatinine, NGAL, galectin-3, and urea. Higher PENK was independently associated with increased risk of deterioration of kidney function between baseline and 9 months (odds ratio, 1.29 [1.02–1.65] per PENK doubling; P=0.038; defined as >25% decrease in estimated glomerular filtration rate) and mortality (hazard ratio, 1.23 [1.07–1.43] per doubling; P=0.004). Analyses in the validation cohort yielded comparable findings.Conclusions:Higher PENK levels are associated with more severe HF, with glomerular and tubular renal dysfunction, with incidence of a deterioration of kidney function, and with mortality. These findings suggest that the opioid system might be involved in deteriorating kidney function in HF.

中文翻译：

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阿片类药物替代物普洛酮可林，可作为一种新型的全面性肾功能衰竭肾标志物

背景：PENK（前脑啡肽）是脑啡肽，内源性阿片肽的稳定替代物，可发挥心压作用并改善肾脏功能。PENK与心力衰竭（HF）的严重程度和肾功能不全相关。因此，我们假设PENK可能与肾功能恶化有关，并且可能在HF中起新的肾脏标志物的作用。方法和结果：在2180名大型多中心队列的HF患者中（BIOSTAT-CHF [A Systems Biology Study to [针对慢性心力衰竭的量身定制治疗]），PENK与临床变量，血浆和尿液生物标志物以及临床终点之间的关系已建立。在1703名HF患者的单独队列中验证了数据。1245名患者（57％）的PENK升高（> 80 pmol / L，第99个百分点）。较高的PENK与更晚期的HF和肾小球和肾小管功能障碍有关。PENK的最强独立预测因子是估计的肾小球滤过率。其他的是血浆NGAL（中性粒细胞明胶酶相关的脂蛋白）和NT-proBNP（N端pro-B型利尿钠肽；所有P <0.001）。使用相关热图和层次聚类分析，将PENK与估计的肾小球滤过率，肌酐，NGAL，galectin-3和尿素聚类。较高的PENK独立地与基线至9个月之间肾功能恶化的风险增加相关（赔率比，每PENK加倍1.29 [1.02-1.65]；P = 0.038；定义为估计的肾小球滤过率降低> 25％）和死亡率（危险率，每增加一倍1.23 [1.07–1.43]；P= 0.004）。结论：结论：较高的PENK水平与更严重的心衰，肾小球和肾小管肾功能不全，肾功能恶化的发生率以及死亡率有关。这些发现表明，阿片样物质系统可能参与了HF患者肾功能的恶化。