神经肽 Y 与慢性肾脏病进展：一项队列研究。

Neuropeptide Y and chronic kidney disease progression: a cohort study.

机构信息

CNR-IFC, Center of Clinical Physiology, Clinical Epidemiology of Renal Diseases and Hypertension, Reggio Calabria, Italy.

Radboud University Nijmegen Medical Centre (Radboudumc), Nijmegen, The Netherlands.

出版信息

Nephrol Dial Transplant. 2018 Oct 1;33(10):1805-1812. doi: 10.1093/ndt/gfx351.

DOI:10.1093/ndt/gfx351

PMID:29370406

Abstract

BACKGROUND

Neuropeptide Y (NPY) is a sympathetic neurotransmitter that has been implicated in various disorders including obesity, gastrointestinal and cardiovascular diseases.

METHODS

We investigated the relationship between circulating NPY and the progression of the glomerular filtration rate (GFR) and proteinuria and the risk for a combined renal endpoint (>30% GFR loss, dialysis/transplantation) in two European chronic kidney disease (CKD) cohorts including follow-up of 753 and 576 patients for 36 and 57 months, respectively.

RESULTS

Average plasma NPY was 104 ± 32 pmol/L in the first CKD cohort and 119 ± 41 pmol/L in the second one. In separate analyses of the two cohorts, NPY associated with the progression of the estimated GFR (eGFR) and proteinuria over time in both unadjusted and adjusted {eGFR: -3.60 mL/min/1.73 m2 [95% confidence interval (CI): -4.46 to - 2.74] P < 0.001 and -0.83 mL/min/1.73 m2 (-1.41 to - 0.25, P = 0.005); proteinuria: 0.18 g/24 h (0.11-0.25) P < 0.001 and 0.07 g/24 h (0.005-0.14) P = 0.033} analyses by the mixed linear model. Accordingly, in a combined analysis of the two cohorts accounting for the competitive risk of death (Fine and Gray model), NPY predicted (P = 0.005) the renal endpoint [sub-distribution hazard ratio (SHR): 1.09; 95% CI: 1.03-1.16; P = 0.005] and the SHR in the first cohort (1.14, 95% CI: 1.04-1.25) did not differ (P = 0.25) from that in the second cohort (1.06, 95% CI: 0.98-1.15).

CONCLUSIONS

NPY associates with proteinuria and faster CKD progression as well as with a higher risk of kidney failure. These findings suggest that the sympathetic system and/or properties intrinsic to the NPY molecule may play a role in CKD progression.

摘要

背景

神经肽 Y（NPY）是一种交感神经递质，与多种疾病有关，包括肥胖、胃肠道和心血管疾病。

方法

我们研究了循环 NPY 与肾小球滤过率（GFR）和蛋白尿进展的关系，以及在两个欧洲慢性肾脏病（CKD）队列中，发生联合肾脏终点（GFR 损失>30%、透析/移植）的风险，其中两个队列的随访时间分别为 753 名和 576 名患者 36 个月和 57 个月。

结果

第一队列的平均血浆 NPY 为 104±32 pmol/L，第二队列为 119±41 pmol/L。在两个队列的单独分析中，NPY 与未经调整和调整后的 eGFR 和蛋白尿随时间的进展相关{ eGFR：-3.60 mL/min/1.73 m2 [95%置信区间（CI）：-4.46 至-2.74] P<0.001 和-0.83 mL/min/1.73 m2（-1.41 至-0.25，P=0.005）；蛋白尿：0.18 g/24 h（0.11-0.25）P<0.001 和 0.07 g/24 h（0.005-0.14）P=0.033}。因此，在考虑死亡竞争风险的两个队列的综合分析中（Fine 和 Gray 模型），NPY 预测（P=0.005）肾脏终点[亚分布风险比（SHR）：1.09；95%CI：1.03-1.16；P=0.005]，且第一队列的 SHR（1.14，95%CI：1.04-1.25）与第二队列（1.06，95%CI：0.98-1.15）的 SHR 无差异（P=0.25）。