Trefoil Factor 1 Excretion Is Increased in Early Stages of Chronic Kidney Disease.
Trefoil Factor 1 Excretion Is Increased in Early Stages of Chronic Kidney Disease.
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DOI：
10.1371/journal.pone.0138312
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Roth GA
中科院分区：
文献类型：
--
作者：
Lebherz-Eichinger D;Tudor B;Ankersmit HJ;Reiter T;Haas M;Roth-Walter F;Krenn CG;Roth GA
慢性肾脏疾病（CKD）与高发病率和死亡率相关。在许多患者中，慢性肾病是在疾病进展晚期才被诊断出来的。因此，潜在生物标志物的实施可能有助于早期识别有风险的个体。三叶因子家族（TFF）肽促进粘膜上皮的恢复过程，并在尿路中大量存在。因此，我们试图研究CKD患者的TFF肽水平及其作为CKD生物标志物的潜力。我们用ELISA法分析了115例无透析的CKD 1-5期患者血清和尿液中TFF1和TFF3的含量。20名健康志愿者作为对照。我们的研究结果显示，与对照组相比，尿TFF1水平在1-4期CKD发病时显著升高，在疾病进展过程中下降（p = 0.003, < 0.001, 0.005和0.007）。中位浓度：对照组为3.5 pg/mL， CKD组为165.2、61.1、17.2和15.8 pg/mL（1-4）。与对照组相比，3-5期患者血清TFF1和TFF3水平显著升高（TFF1: p < 0.01； CKD 3-5期患者中位浓度分别为12.1、39.7和34.5 pg/mL）。TFF3: p < 0.001；中位浓度：对照组为7.1 ng/mL， CKD组为26.1、52.8和78.8 ng/mL（3-5）。TFF3排泄在第4期和第5期增加（p < 0.001；尿中位数水平：对照组65.2 ng/mL， CKD 4/5组231.5 ng/mL和382.6 ng/mL；部分TFF3排泄：对照组6.4 vs CKD 4/5组19.6 ng/mL和44.1）。ROC曲线分析显示，监测TFF肽水平可预测不同CKD分期（AUC尿/血清TFF > 0.8）。总之，我们的研究结果表明，在CKD较低阶段，尿TFF1明显升高，CKD患者TFF1和TFF3水平升高。此外，ROC曲线分析显示，TFF1和TFF3似乎受到不同的调控，并具有预测不同CKD分期的潜力。
Chronic kidney disease (CKD) is associated with high morbidity and mortality. In many patients CKD is diagnosed late during disease progression. Therefore, the implementation of potential biomarkers may facilitate the early identification of individuals at risk. Trefoil factor family (TFF) peptides promote restitution processes of mucous epithelia and are abundant in the urinary tract. We therefore sought to investigate the TFF peptide levels in patients suffering from CKD and their potential as biomarkers for CKD. We analysed TFF1 and TFF3 in serum and urine of 115 patients with CKD stages 1–5 without dialysis by ELISA. 20 healthy volunteers served as controls. Our results showed, that urinary TFF1 levels were significantly increased with the onset of CKD in stages 1–4 as compared to controls and declined during disease progression (p = 0.003, < 0.001, 0.005, and 0.007. median concentrations: 3.5 pg/mL in controls vs 165.2, 61.1, 17.2, and 15.8 pg/mL in CKD 1–4). TFF1 and TFF3 serum levels were significantly elevated in stages 3–5 as compared to controls (TFF1: p < 0.01; median concentrations: 12.1, 39.7, and 34.5 pg/mL in CKD 3–5. TFF3: p < 0.001; median concentrations: 7.1 ng/mL in controls vs 26.1, 52.8, and 78.8 ng/mL in CKD 3–5). TFF3 excretion was increased in stages 4 and 5 (p < 0.001; median urinary levels: 65.2 ng/mL in controls vs 231.5 and 382.6 ng/mL in CKD 4/5; fractional TFF3 excretion: 6.4 in controls vs 19.6 and 44.1 in CKD 4/5). ROC curve analyses showed, that monitoring TFF peptide levels can predict various CKD stages (AUC urinary/serum TFF > 0.8). In conclusion our results show increased levels of TFF1 and TFF3 in CKD patients with a pronounced elevation of urinary TFF1 in lower CKD stages. Furthermore, TFF1 and TFF3 seems to be differently regulated and show potential to predict various CKD stages, as shown by ROC curve analysis.