Metabolomic Markers of Kidney Function Decline in Patients With Diabetes: Evidence From the Chronic Renal Insufficiency Cohort (CRIC) Study.
Metabolomic Markers of Kidney Function Decline in Patients With Diabetes: Evidence From the Chronic Renal Insufficiency Cohort (CRIC) Study.
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DOI：
10.1053/j.ajkd.2020.01.019
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发表时间：
2020-10
期刊：
影响因子：
--
通讯作者：
CRIC Study Investigators
中科院分区：
文献类型：
--
作者：
Kwan B;Fuhrer T;Zhang J;Darshi M;Van Espen B;Montemayor D;de Boer IH;Dobre M;Hsu CY;Kelly TN;Raj DS;Rao PS;Saraf SL;Scialla J;Waikar SS;Sharma K;Natarajan L;CRIC Study Investigators
需要提供未来糖尿病肾病(DKD)可靠证据的生物标记物来改善疾病管理。在一项横断面研究中，我们先前确定了与健康对照组相比，DKD患者的13种尿代谢物减少。在这里，我们评估了这13种代谢物与未来DKD进展的相关性。未来的队列。1001名慢性肾功能不全(CRIC)的糖尿病患者，估计肾小球滤过率(EGFR)在20-70ml/min/1.73m2之间，前瞻性地跟踪观察了中位数8年(范围：2-10年)。13种尿代谢物，年龄，种族，性别，一生中抽过100支香烟，体重指数，血红蛋白A1c，血压，尿白蛋白和EGFR。使用替代疗法(KFRT；即开始透析或接受移植)的年度EGFR斜率和发生肾功能衰竭的时间。通过逐步选择和惩罚回归，建立了几个临床代谢物模型，将EGFR斜率作为结果，并进一步测试了KFRT的结果。基于EGFR斜率的高预测精度和KFRT事件的高一致性统计，选择了最好的交叉验证(最终)预后模型。随访期间，平均−斜率为1.83+/−1.92(SD)ml/−/1.73m2/年，359例(36%)患者经历了KFRT。从进入CRIC研究的时间到KFRT的中位时间为7.45年。在我们的最终模型中，在调整了临床变量后，代谢产物3-羟基异丁酸(3-HIBA)和3-甲基巴豆甘氨酸与EGFR斜率呈显著负相关，而柠檬酸和乌头酸呈正相关。此外，3-HiBA和乌头酸分别与KFRT的高风险和低风险相关(RR分别为2.34[95%CI，1.51~3.62]和0.70[95%CI，0.51~0.95])。通过流动注射分析和两阶段建模方法，代谢物特征可能不是最佳的、非靶向代谢组学的亚群。尿液中的代谢物可能有助于了解DKD的进展情况。如果在未来的研究中复制，乌头酸和3-HiBA可以确定糖尿病患者的GFR下降的高风险，潜在地导致改善临床护理和靶向治疗。
Biomarkers that provide reliable evidence of future diabetic kidney disease (DKD) are needed to improve disease management. In a cross-sectional study, we previously identified thirteen urine metabolites that were reduced in DKD compared with healthy controls. Here, we evaluated associations of these thirteen metabolites with future DKD progression. Prospective cohort. 1001 Chronic Renal Insufficiency Cohort (CRIC) participants with diabetes with estimated glomerular filtration rate (eGFR) between 20 and 70 ml/min/1.73m2 were followed prospectively for a median of 8 (range: 2–10) years. Thirteen urine metabolites, age, race, sex, smoked >100 cigarettes in lifetime, body mass index, hemoglobin A1c, blood pressure, urine albumin, and eGFR. Annual eGFR slope and time to incident kidney failure with replacement therapy (KFRT; ie, initiation of dialysis or receipt of transplant). Several clinical-metabolite models were developed for eGFR slope as the outcome via stepwise selection and penalized regression, and further tested on the time-to-KFRT outcome. A best cross-validated (final) prognostic model was selected based on high prediction accuracy for eGFR slope and high concordance statistic for incident KFRT. During follow-up, mean eGFR slope was −1.83 +/−1.92 (SD) ml/min/1.73m2 per year; 359 (36%) subjects experienced KFRT. Median time-to-KFRT was 7.45 years from the time of entry to the CRIC Study. In our final model, after adjusting for clinical variables, metabolites 3-hydroxyisobutyrate (3-HIBA) and 3-methylcrotonyglycine had a significant negative association with eGFR slope, whereas citric and aconitic acid were positively associated. Further, 3-HIBA and aconitic acid were associated with higher and lower risk of KFRT, respectively (HRs of 2.34 [95% CI, 1.51–3.62] and 0.70 [95% CI, 0.51–0.95]). Subgroups for whom metabolite signatures may not be optimal, non-targeted metabolomics by flow-injection analysis and two-stage modeling approaches. Urine metabolites may offer insights into DKD progression. If replicated in future studies, aconitic acid and 3-HIBA could identify individuals with diabetes at high risk of GFR decline, potentially leading to improved clinical care and targeted therapies.
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DOI：
10.1053/j.ajkd.2018.02.361
发表时间：
2018-10
期刊：
American journal of kidney diseases : the official journal of the National Kidney Foundation
影响因子：
--
作者：
Harhay MN;Xie D;Zhang X;Hsu CY;Vittinghoff E;Go AS;Sozio SM;Blumenthal J;Seliger S;Chen J;Deo R;Dobre M;Akkina S;Reese PP;Lash JP;Yaffe K;Kurella Tamura M;CRIC Study Investigators
通讯作者：
CRIC Study Investigators
影响因子：
11.1
作者：
Hallan S;Afkarian M;Zelnick LR;Kestenbaum B;Sharma S;Saito R;Darshi M;Barding G;Raftery D;Ju W;Kretzler M;Sharma K;de Boer IH
通讯作者：
de Boer IH
DOI：
10.2215/cjn.04260415
发表时间：
2015-11-01
影响因子：
9.8
作者：
Denker, Matthew;Boyle, Suzanne;Feldman, Harold I.
通讯作者：
Feldman, Harold I.
影响因子：
5
作者：
KAMERLING, JP;GERWIG, GJ;WADMAN, SK
通讯作者：
WADMAN, SK
影响因子：
7.4
作者：
Fuhrer, Tobias;Heer, Dominik;Zamboni, Nicola
通讯作者：
Zamboni, Nicola