Serum metabolites are associated with all-cause mortality in chronic kidney disease.
Serum metabolites are associated with all-cause mortality in chronic kidney disease.
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DOI：
10.1016/j.kint.2018.03.008
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发表时间：
2018-08
影响因子：
19.6
通讯作者：
Grams ME
中科院分区：
文献类型：
--
作者：
Hu JR;Coresh J;Inker LA;Levey AS;Zheng Z;Rebholz CM;Tin A;Appel LJ;Chen J;Sarnak MJ;Grams ME
慢性肾病（CKD）涉及显着的代谢异常并且死亡率很高。由于 CKD 患者的血清代谢物水平可能有助于了解亚临床疾病状态和未来死亡风险，因此我们使用发现和复制设计确定了哪些血清代谢物与 CKD 死亡率可重复相关。在肾病饮食调整 (MDRD) 研究中，通过非靶向液相色谱和质谱对 299 名 CKD 患者的血清样本进行代谢水平定量，作为发现队列。在调整人口统计和临床协变量（包括尿蛋白和测量的肾小球滤过率）后，622 种代谢物中的 6 种与死亡率显着相关，中位随访时间为 17 年。然后，我们在中位随访 10 年的时间里，对非裔美国人肾脏病和高血压研究 (AASK) 队列中的 963 名 CKD 患者复制了与死亡率的关联。 MDRD 队列中确定的六种代谢物中的三种在 AASK 队列中得到了复制：富马酸盐、尿囊素和核糖酸盐，分别属于能量、核苷酸和碳水化合物途径。两项研究和荟萃分析中的点估计相似（代谢物每倍增，调整后的风险比分别为 1.63、1.59 和 1.61）。因此，在两个特征明确的队列中，选定的血清代谢物与 CKD 长期死亡率的关系超出了肾功能标志物的可重复性，为研究提供了目标。
Chronic kidney disease (CKD) involves significant metabolic abnormalities and has a high mortality rate. Because the levels of serum metabolites in patients with CKD might provide insight into subclinical disease states and risk for future mortality, we determined which serum metabolites reproducibly associate with mortality in CKD using a discovery and replication design. Metabolite levels were quantified via untargeted liquid chromatography and mass spectroscopy from serum samples of 299 patients with CKD in the Modification of Diet in Renal Disease (MDRD) study as a discovery cohort. Six among 622 metabolites were significantly associated with mortality over a median follow-up of 17 years after adjustment for demographic and clinical covariates, including urine protein and measured glomerular filtration rate. We then replicated associations with mortality in 963 patients with CKD from the African American Study of Kidney Disease and Hypertension (AASK) cohort over a median follow-up of ten years. Three of the six metabolites identified in the MDRD cohort replicated in the AASK cohort: fumarate, allantoin, and ribonate, belonging to energy, nucleotide, and carbohydrate pathways, respectively. Point estimates were similar in both studies and in meta-analysis (adjusted hazard ratios 1.63, 1.59, and 1.61, respectively, per doubling of the metabolite). Thus, selected serum metabolites were reproducibly associated with long-term mortality in CKD beyond markers of kidney function in two well characterized cohorts, providing targets for investigation.
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影响因子：
8.2
作者：
Ng, D. P. K.;Salim, A.;Ong, C. N.
通讯作者：
Ong, C. N.
DOI：
10.1097/01.asn.0000070081.15137.c0
发表时间：
2003-07-01
影响因子：
13.6
作者：
Appel, LJ;Middleton, J;Wright, JT
通讯作者：
Wright, JT
影响因子：
5
作者：
Babizhayev, MA;Yermakova, VN;Zheltukhina, GA
通讯作者：
Zheltukhina, GA
影响因子：
8.6
作者：
Dehaven CD;Evans AM;Dai H;Lawton KA
通讯作者：
Lawton KA
影响因子：
3.7
作者：
Hill NR;Fatoba ST;Oke JL;Hirst JA;O'Callaghan CA;Lasserson DS;Hobbs FD
通讯作者：
Hobbs FD