有兴趣识别新的过滤标记,导致比目前的标记(肌酐和胱抑素C)更准确的GFR估计,并且在人口统计学群体中更一致。我们假设大规模代谢组学可以识别受肾小球滤过率(GFR)强烈影响的血清代谢物,并且在人口统计学变量中比肌酐更一致。这将是未来研究的有希望的过滤标记。
■我们评估了测得的GFR(mGFR)与887常见,通过非靶向的基于色谱和光谱的代谢组学平台(Metabolon)对580名儿童慢性肾脏病(CGiD)参与者的冷冻血液样本进行定量,674名参与者在肾脏疾病(MDRD)研究和962名参与者在非裔美国人肾脏疾病和高血压研究(AASK)。我们评估了代谢物-mGFR与代谢物类别的相关性,分子量,测定平台和测量变异系数(CV)。在与mGFR呈强负相关(r<-0.5)的代谢物中,我们评估了年龄(儿童身高)的额外变化,性别,种族和体重指数(BMI)。
■共有561种代谢物(63%)与mGFR呈负相关。与mGFR的相关性在整个研究中高度一致,性别,种族和BMI类别(代谢物-mGFR相关性在0.88和0.95之间)。氨基酸,与脂质相比,碳水化合物和核苷酸更经常与mGFR呈负相关,但是与代谢物的分子量无关,液相色谱/质谱平台和测量CV。在与mGFR(r<-0.5)具有强负相关的114种代谢物中,27与年龄(儿童身高)无关,性别或种族。
■大多数代谢物与mGFR的相关性在性别之间呈负相关且一致,种族,BMI和研究。与mGFR具有一致的强负相关且与人口统计学变量不相关的代谢物可能代表候选标志物以改善GFR的估计。
UNASSIGNED: There is interest in identifying novel filtration markers that lead to more accurate
GFR estimates than current markers (creatinine and cystatin C) and are more consistent across demographic groups. We hypothesize that large-scale metabolomics can identify serum metabolites that are strongly influenced by glomerular filtration rate (
GFR) and are more consistent across demographic variables than creatinine, which would be promising filtration markers for future investigation.
UNASSIGNED: We evaluated the consistency of associations between measured
GFR (mGFR) and 887 common, known metabolites quantified by an untargeted chromatography- and spectroscopy-based metabolomics platform (Metabolon) performed on frozen blood samples from 580 participants in Chronic Kidney Disease in Children (CKiD), 674 participants in Modification of Diet in Renal Disease (MDRD) Study and 962 participants in African American Study of Kidney Disease and Hypertension (AASK). We evaluated metabolite-mGFR correlation association with metabolite class, molecular weight, assay platform and measurement coefficient of variation (CV). Among metabolites with strong negative correlations with mGFR (r < -0.5), we assessed additional variation by age (height in children), sex, race and body mass index (BMI).
UNASSIGNED: A total of 561 metabolites (63%) were negatively correlated with mGFR. Correlations with mGFR were highly consistent across study, sex, race and BMI categories (correlation of metabolite-mGFR correlations between 0.88 and 0.95). Amino acids, carbohydrates and nucleotides were more often negatively correlated with mGFR compared with lipids, but there was no association with metabolite molecular weight, liquid chromatography/mass spectrometry platform and measurement CV. Among 114 metabolites with strong negative associations with mGFR (r < -0.5), 27 were consistently not associated with age (height in children), sex or race.
UNASSIGNED: The majority of metabolite-mGFR correlations were negative and consistent across sex, race, BMI and study. Metabolites with consistent strong negative correlations with mGFR and non-association with demographic variables may represent candidate markers to improve estimation of
GFR.